[An observational and Mendelian randomization study of the associations of body mass index with plasma amino acids and acylcarnitines in Chinese adults].

Objective: To explore the relationship between BMI and levels of plasma amino acids and acylcarnitines in Chinese adults. Methods: Based on 2 182 individuals with targeted mass spectrometry metabolomic measurements from the first resurvey of the China Kadoorie Biobank, we assessed the linear and nonlinear associations between BMI and plasma levels of 20 amino acids and 40 acylcarnitines using linear regression models and restricted cubic spline models, and identified BMI-related metabolic pathways. We conducted one-sample Mendelian randomization (MR) with BMI genetic risk scores as the instrumental variable further to explore the potential causal relationships between BMI and 20 amino acids and 40 acylcarnitines, and tested for horizontal pleiotropy using the MR-Egger method. Results: Observational analyses found that BMI was associated with increased plasma levels of 3 branched-chain amino acids (isoleucine, leucine, and valine), 2 aromatic amino acids (phenylalanine and tyrosine), 3 other amino acids (cysteine, glutamate, lysine), and 7 acylcarnitines (C3, C4, C5, C10, C10:1, C14, and C16), and with decreased circulating levels of asparagine, serine, and glycine. Pathway analysis identified 7 BMI-related amino acids metabolic pathways (false discovery rate corrected all P<0.05), including branched-chain amino acids and aromatic amino acids biosynthesis, glutathione metabolism, etc. BMI showed a nonlinear relationship with leucine, valine, and threonine, and a linear relationship with other amino acids and acylcarnitines. One-sample MR analyses revealed that BMI was associated with elevated levels of tyrosine and 4 acylcarnitines [C5-DC(C6-OH), C5-M-DC, C12-DC, and C14], with tyrosine and acylcarnitine C14 positively correlated with BMI in both observational [the ß values (95%CIs) were 0.057 (0.044-0.070) and 0.018 (0.005-0.032), respectively] and One-sample MR analyses [the ß values (95%CIs) were 0.102 (0.035-0.169) and 0.104 (0.036-0.173), respectively]. The MR analyses of the current study satisfied the 3 core assumptions of instrumental variable. Conclusions: BMI was associated with circulating 11 amino acids and 7 acylcarnitines in Chinese adults, involving several pathways such as branched-chain amino acid and aromatic amino acid metabolism, fatty acid metabolism, and oxidative stress. There may be a causal relationship between BMI and tyrosine and acylcarnitine C14.

[Current status of tuberculosis burden in China].

Tuberculosis, caused by Mycobacterium tuberculosis, is an infectious disease that most often affects the lungs. China is still among the high-burden tuberculosis countries in the world. Although the estimated incidence of tuberculosis in China has declined in recent years, the declining rate is slow. It still faces major issues such as a slower rate of decline, a widening gap between estimated and notified incidence, higher risk among middle-aged and older adults, a high number of cases among agriculture and related workers, and a heavier disease burden in the country's western regions. In addition, latent tuberculosis infection, drug-resistant tuberculosis, tuberculosis coinfection with HIV, and extrapulmonary tuberculosis have also exacerbated the disease burden of tuberculosis to some extent. This paper reviewed the epidemic characteristics of tuberculosis, the epidemiological triad, three links and two factors in the transmission process, the disease burden, and other aspects to provide a reference for formulating prevention and control strategies on tuberculosis.

[Tea consumption and cancer: a Mendelian randomization study].

Objective: A Mendelian randomization (MR) analysis was performed to assess the relationship between tea consumption and cancer. Methods: There were 100 639 participants with the information of gene sequencing of whole genome in the China Kadoorie Biobank. After excluding those with cancer at baseline survey, a total of 100 218 participants were included in this study. The baseline information about tea consumption were analyzed, including daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption. We used the two-stage least square method to evaluate the associations between three tea consumption variables and incidence of cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer. Multivariable MR and analysis only among nondrinkers were used to control the impact of alcohol consumption. Sensitivity analyses were also performed, including inverse variance weighting, weighted median, and MR-Egger. Results: We used 54, 42, and 28 SNPs to construct non-weighted genetic risk scores as instrumental variables for daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption, respectively. During an average of (11.4±3.0) years of follow-up, 6 886 cases of cancer were recorded. After adjusting for age, age2, sex, region, array type, and the first 12 genetic principal components, there were no significant associations of three tea consumption variables with the incidence of cancer and cancer subtypes. Compared with non-daily tea drinkers, the HR (95%CI) of daily tea drinkers for cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer, are respectively 0.99 (0.78-1.26), 1.17 (0.58-2.36), 0.86 (0.40-1.84), 0.85 (0.42-1.73), 1.39 (0.85-2.26) and 0.63 (0.28-1.38). After controlling the impact of alcohol consumption and performing multiple sensitivity analyses, the results were similar. Conclusion: There is no causal relationship between tea consumption and risk of cancer in population in China.

[A descriptive analysis on hypertension in adult twins in China].

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.

[A descriptive analysis of hyperlipidemia in adult twins in China].

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.

[Review of genome-wide association research of aging phenotypes].

"Active health" has been emphasized in "Healthy China 2030" in dealing with the challenges of population aging, so the anti-aging strategies are requires to be more precise and effective at both individual and population levels. Aging is influenced by both genetic and environmental factors. In the recent 20 years, the research of genetics of human ageing has been greatly facilitated owning to the development of high-throughput sequencing techniques, statistical methodology for multi-omics data, as well as the growing qualified evidence of large-scale population-based genomic research. This paper provides a review of genome-wide association research of aging.

[Heritability and genetic correlation of body mass index and coronary heart disease in Chinese adult twins].

Objective: To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation. Methods: Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD. Results: A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95%CI: 0.49-0.55) and 0.76 (95%CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD (rA=0.10, 95%CI:0.02-0.17). Conclusion: In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

[Trend analysis of influenza vaccination among hospitalized elderly people in Beijing, 2013-2019].

OBJECTIVE: To analyze the influenza vaccination trend of hospitalized elderly people (≥ 60 years old) in Beijing from 2013 to 2019. METHODS: The influenza vaccination status and hospitalization information of elderly people were extracted from the Beijing Elderly Influenza Vaccination database (2013-2019) and the Beijing Urban Employee Basic Medical Insurance database (2013-2019), se-parately. The influenza vaccine coverage rates and annual percentage change were calculated to compare the vaccination trends of elderly people hospitalized due to different diseases. The subjects in 2018-2019 influenza season were divided into different groups according to demographic status, health conditions and hospitalization outcomes to describe and compare the distribution of influenza vaccination rates. RESULTS: The influenza vaccine coverage rates among the elderly people hospitalized due to cardiovascular diseases, cerebrovascular diseases, respiratory diseases or diabetes mellitus were 14.6%, 13.4%, 13.4% and 11.8%, respectively. The influenza vaccination rate among those hospitalized for cardiovascular diseases remained the highest across six influenza seasons and those hospitalized for diabetes mellitus remained the lowest. The largest annual decline of influenza vaccine coverage rate was observed among the hospitalized elderly due to diabetes mellitus (-7.85%). The distribution of vaccinated population was significantly associated with age, gender, hospitalization outcome and comorbidities among the hospitalized elderly people with specific diseases in 2018-2019. Among the elderly people hospitalized due to four different diseases, the vaccination rate of the patients aged 70-79 years was higher than that of the other age groups and that of the patients aged 60-69 years was the lowest. Among the elderly people hospitalized due to respiratory diseases, the vaccination rate of men was higher than that of women, while the situation reversed among the elderly people hospitalized due to cardiovascular diseases and diabetes mellitus. Vaccination rates decreased among the older adults with poor hospitalization outcomes. Among the elderly people hospitalized due to diabetes mellitus, those with 0 comorbidity had the lowest vaccination rate (7.9%). CONCLUSION: The trend of influenza vaccine coverage rates among the elderly people in Beijing from 2013 to 2019 was downward. We should pay more attention to influenza vaccination in elderly people with diabetes mellitus and aged 60-69 years, and carry out more research on the protective effects of influenza vaccine to promote influenza vaccine coverage among people with chronic diseases.

[Gene-lifestyle interaction on coronary heart disease in adult twins of China].

Objective: To explore the gene-lifestyle interaction on coronary heart disease (CHD) in adult twins of China. Methods: Participants were selected from twin pairs registered in the Chinese National Twin Registry (CNTR). Univariate interaction model was used to estimate the interaction, via exploring the moderation effect of lifestyle on the genetic variance of CHD. Results: A total of 20 477 same-sex twin pairs aged ≥25 years were recruited, including 395 CHD cases, and 66 twin pairs both had CHD. After adjustment for age and sex, no moderation effects of lifestyles, including current smoking, current drinking, physical activity, intake of vegetable and fruit, on the genetic variance of CHD were found (P>0.05), suggesting no significant interactions. Conclusion: There was no evidence suggesting statistically significant gene-lifestyle interaction on CHD in adult twins of China.

[Associations of lifestyles with major chronic diseases in Chinese adults: evidence from the China Kadoorie Biobank].

Major chronic diseases, including cardiovascular disease, diabetes, cancer, and respiratory disease, cause substantial mortality and morbidity in China. Evidence from Western population showed that smoking, excessive alcohol intake, physical inactivity, unhealthful dietary habits and adiposity are independent risk factors for major chronic diseases. However, because of the vast differences in lifestyles and disease patterns, evidence from Western populations may not be generalizable to the Chinese population. Assessing the directions and magnitude of associations between lifestyles and major chronic diseases is crucial to evaluate the benefits yielded from lifestyle modifications, thus informing related guidelines. In recent years, prospective cohort studies in China, including the China Kadoorie Biobank (CKB), have shown relationships between unfavorable lifestyle factors and major chronic diseases. In particular, the CKB study has laid the evidence base for lifestyle factors (occupational physical activity) and diseases (hemorrhagic stroke, gastrointestinal cancers, and chronic obstructive pulmonary disease) unique to the Chinese population. This article aims to summarize the research findings on this topic.

[A multi-omics approach to investigate the etiology of non-communicable diseases: recent advance and applications].

One of the main aims of chronic disease epidemiology is to explore the etiological factors of diseases. Multi-omics includes all genes (genomics), extensive changes in gene expression (epigenetics), ribonucleic acids (transcriptomics), and proteins (proteomics) generated during the process of DNA replication, transcription, translation, and post-translational modification, as well as small molecule metabolites downstream (metabolomics). Multi-omics platforms provide technical support for assessing omics biomarkers including genomics, transcriptomics, and proteomics, while systems epidemiology provides theoretical and methodological support for using multi-omics to conduct etiological research. Multi-omics research not only reveals the interaction network between molecules, but also contributes to causal inference from the molecular level. With the global exponential growth of publicly available data, analysis platforms, and consortia, resources for multi-omics research will become more abundant, and the depth and breadth of research will be greatly expanded. This article will review the applications of multi-omics approach in the etiologic research on non-communicable diseases, representative research in the past three years, opportunities and challenges for large-scale cohort studies, advantages and issues of multi-omics research in the Chinese population, and future perspectives.

Involvement of LeMRP, an ATP-binding cassette transporter, in shikonin transport and biosynthesis in Lithospermum erythrorhizon.

Shikonin and its derivatives are important medicinal secondary metabolites accumulating in roots of Lithospermum erythrorhizon. Although some membrane proteins have been identified as transporters of secondary metabolites, the mechanisms underlying shikonin transport and accumulation in L. erythrorhizon cells still remain largely unknown. In this study, we isolated a cDNA encoding LeMRP, an ATP-binding cassette transporter from L. erythrorhizon, and further investigated its functions in the transport and biosynthesis of shikonin using the yeast transformation and transgenic hairy root methods, respectively. Real-time PCR was applied for expression analyses of LeMRP and shikonin biosynthetic enzyme genes. Functional analysis of LeMRP using the heterologous yeast cell expression system showed that LeMRP could be involved in shikonin transport. Transgenic hairy roots of L. erythrorhizon demonstrated that LeMRP overexpressing hairy roots produced more shikonin than the empty vector (EV) control. Real-time PCR results revealed that the enhanced shikonin biosynthesis in the overexpression lines was mainly caused by highly up-regulated expression of genes coding key enzymes (LePAL, HMGR, Le4CL and LePGT) involved in shikonin biosynthesis. Conversely, LeMRP RNAi decreased the accumulation of shikonin and effectively down-regulated expression level of the above genes. Typical inhibitors of ABC proteins, such as azide and buthionine sulphoximine, dramatically inhibited accumulation of shikonin in hairy roots. Our findings provide evidence for the important direct or indirect role of LeMRP in transmembrane transport and biosynthesis of shikonin.

[An adolescent with Hashimoto's encephalopathy after surgery and ¹³¹I radiotherapy for papillary thyroid carcinoma: one case report].

Hashimoto's encephalopathy is a rare brain disease. Its etiology is still unknown. In this paper, we reported a 15-year-old female patient underwent total thyroidectomy and lymph node dissection, due to a multifocal papilliferous carcinoma of the right lobus. Forty-two days after surgery, the patient was treated by ¹³¹I radiotherapy in another hospital and begun to have a headache after 48 hours. At last, the patient was diagnosed by HE on the basis of all considerations. She recovered from by i.v. Immunoglobulin. Till now, the patient has not relapsed for more than 4 years follow-up.

[Clinical treatment of metastatic papillary thyroid carcinoma in cervical lymph nodal with occult primary sites].

Objective:To discuss the diagnosis, treatment and prognosis of metastatic papillary thyroid carcinoma in cervical lymph nodal with occult primary sites. Method:The clinical data of 5 patients involved papillary thyroid carcinoma with cervical lymph nodal metastasis with occult primary sites from 2009 to 2015 were analyzed. Result:According to preoperation examinations, two of them only underwent neck lymph node resection and three patients underwent asubtotal or total thyroidectomy plus neck lymph node dissection. All the pathological results showed that there were metastatic papillary thyroid carcinoma in cervical lymph nodal, but the primary sites of thyroid tissue were normal. After 1 to 7 year follow-up, there was no recurrence. Conclusion:Whether to take the thyroidectomy need to be carefully considered thyroidectomy in patients with metastatic papillary thyroid carcinoma in cervical lymph nodal with occult primary sites.

[An analysis of spectrum of allergen sensitization among patients with tree pollen allergy in Beijing].

Objective:To explore the feature of allergic sensitization of tree pollen and the relationship between tree pollen and airborne pollen in Beijing. Method:Two thousand five hundred and twenty-one patients with allergic diseases were enrolled between January to July in 2017 in an allergy department. All patients received SPT of 8 kinds of tree pollen. Result:①The overall tree pollen positive rate of SPT was 49.3% (1 244/2 521). Male had a higher positive rate than female (56.4% vs 45.0%, P<0.01) while child group had a higher positive rate than adult group (55.9% vs 48.6%, P<0.05). The poly sensitization was observed with a rate of 26.3%, take the percentage of 53.3% of the overall positive subjects. ②The highest sensitization rate was found in March (62.2%), followed by May (52.1%), the lowest was January (27.9%). There was a positive correlation between tree pollen sensitization rate and pollen count of each month (r=0.929, P<0.01). ③Cypress had the highest positive rate (34.6%), followed by poplar (21.3%), the lowest was sophora (13.3%). The sensitization rate was positively correlated with pollen count among different tree pollen (r=0.714, P<0.05). Conclusion:The main allergic pollen in Beijing was cypress. The tree pollen sensitization showed a seasonality with the peak in March. The sensitization status was tightly associated with the amount of airborne pollen.

Inhibitory effect of group II mGluR agonist 2R, 4R-APDC on cell proliferation in dentate gyrus in rats with epileptic seizure.

OBJECTIVE: Epileptic seizure can increase the cell proliferation in dentate gyrus in brain, but the mechanism remains unclear. MATERIALS AND METHODS: In this study, using systemic bromodeoxyuridine (BrdU) to label the dividing cells, the inhibitory effect of group II metabotropic glutamate receptor (mGluR) agonist 2R, 4R-4-aminopyrrolidine-2, 4-dicarboxylate (2R, 4R-APDC) on cell proliferation in dentate gyrus in rats after pilocarpine-induced status epilepticus (SE) was investigated. RESULTS: Results found that, 2R, 4R-APDC could significantly inhibit the behavioral seizure and block the seizure-induced increase of BrdU-positive cells in dentate gyrus, especially in hilus. Double-label immunofluorescence staining showed that, 2R, 4R-APDC did not affect the ability of newborn cells to differentiate into neurons or astrocytes. CONCLUSIONS: 2R, 4R-APDC not only has anticonvulsant effect on adult rats with pilocarpine-induced SE, but also has neuroprotective effect by reducing the abnormal regeneration of nerves.

Nosocomial outbreak of respiratory tract colonization with Mycobacterium fortuitum: demonstration of the usefulness of pulsed-field gel electrophoresis in an epidemiologic investigation.

Between August 1989 and January 1990, 16 patients on an alcoholism rehabilitation ward (ARW) developed positive sputum cultures for Mycobacterium fortuitum. During a 2-wk surveillance period, six of 43 ARW patients but none of 20 staff members had positive sputum cultures. In addition, none of 54 patients and staff on an adjacent ward sharing the same ice machine and water supply had positive cultures, and none of 92 acid-fast bacilli cultures performed on all sputum specimens from all other inpatient sources during the same 2-wk period were positive. The only exposure factor common to all cases was the use of one or both of the ward showers. Compared with 36 ARW control patients, cases were more likely to report clinical criteria for chronic bronchitis (odds ratio, 6.6; 95% confidence interval, 1.5 to 28.6; p = 0.02). Using phenotype analysis, plasmid profiles, and pulsed-field gel electrophoresis of large genomic DNA restriction enzyme fragments, the 16 case isolates were found to be identical. This strain of M. fortuitum was also cultured from a tap connected to the water line supplying the ARW showers, but not from the showers themselves. No further cases were identified after the showers were disconnected and decontaminated. To our knowledge, this is the first clinical use of pulsed-field gel electrophoresis for genetic comparison of mycobacterial strains. It demonstrates the important potential of this technique for studying the epidemiology of mycobacterial infections. Showers should be considered a possible source of nosocomial respiratory tract colonization with M. fortuitum.

Tetracycline resistance in Moraxella (Branhamella) catarrhalis: demonstration of two clonal outbreaks by using pulsed-field gel electrophoresis.

Two tetracycline-resistant (Tcr) Moraxella (Branhamella) catarrhalis strains from England were compared with two previously characterized Tcr Texas strains. Both pairs carried the Tet B determinant, which was nontransferable. Pulsed-field gel electrophoresis of their genomic DNA restriction fragments demonstrated that the strains from the same area were identical (clonal); however, the Texas and English strains differed from each other.

Mercuric reductase activity and evidence of broad-spectrum mercury resistance among clinical isolates of rapidly growing mycobacteria.

Resistance to mercury was evaluated in 356 rapidly growing mycobacteria belonging to eight taxonomic groups. Resistance to inorganic Hg2+ ranged from 0% among the unnamed third biovariant complex of Mycobacterium fortuitum to 83% among M. chelonae-like organisms. With cell extracts and 203Hg(NO3)2 as the substrate, mercuric reductase (HgRe) activity was demonstrable in six of eight taxonomic groups. HgRe activity was inducible and required NADPH or NADH and a thiol donor for optimai activity. Species with HgRe activity were also resistant to organomercurial compounds, including phenylmercuric acetate. Attempts at intraspecies and intragenus transfer of HgRe activity by conjugation or transformation were unsuccessful. Mercury resistance is common in rapidly growing mycobacteria and appears to function via the same inducible enzyme systems already defined in other bacterial species. This system offers potential as a strain marker for epidemiologic investigations and for studying genetic systems in rapidly growing mycobacteria.