[Associations of body mass index and waist circumference with risk of chronic kidney disease in adults in China].

Objective: To examine the associations of BMI and waist circumference (WC) with the risk of chronic kidney disease (CKD) and its subtypes in adults in China. Methods: The data from the China Kadoorie Biobank were used. After excluding those with cancer, coronary heart disease, stroke, or CKD at baseline survey, 480 430 participants were included in this study. Their body height and weight, and WC were measured at baseline survey. Total CKD was defined as diabetic kidney disease (DKD), hypertensive nephropathy (HTN), glomerulonephritis (GN), chronic tubulointerstitial nephritis (CTIN), obstructive nephropathy (ON), CKD due to other causes, and chronic kidney failure. Cox proportional hazards regression model was used to estimate the associations between exposure factors and risks of outcomes. Results: During a follow-up period of (11.8±2.2) years, 5 486 cases of total CKD were identified, including 1 147 cases of DKD, 340 cases of HTN, 1 458 cases of GN, 460 cases of CTIN, 598 cases of ON, 418 cases of CKD due to other causes, and 1 065 cases of chronic kidney failure. After adjusting for socio-demographic factors, lifestyle factors, baseline prevalence of hypertension and diabetes, and WC and compared to participants with normal BMI (18.5-23.9 kg/m2), the hazard ratios (HRs) of total CKD for underweight (<18.5 kg/m2), overweight (24.0-27.9 kg/m2), and obese (≥28.0 kg/m2) were 1.42 (95%CI: 1.23-1.63), 1.00 (95%CI: 0.93-1.08) and 0.98 (95%CI: 0.87-1.10), respectively. Stratification analysis by WC showed that BMI was negatively associated with risk for total CKD in non-central obese participants (WC: <85.0 cm in men and <80.0 cm in women) (HR=0.97, 95%CI: 0.96-0.99), while the association was positive in central obese participants (≥90.0 cm in men and ≥85.0 cm in women) (HR=1.03, 95%CI: 1.01-1.05). The association between BMI and GN was similar to that of total CKD. BMI was associated with an increased risk for HTN, with a HR of 1.12 (95%CI: 1.06-1.18) per 1.0 kg/m2 higher BMI. After adjusting for potential confounders and BMI, compared to participants with non-central obesity, the HRs for pre-central obesity (WC: 85.0-89.9 cm in men and 80.0-84.9 in women) and central obesity were 1.26 (95%CI: 1.16-1.36) and 1.32 (95%CI: 1.20-1.45), respectively. With the exception of HTN and CTIN, WC was positively associated with risks for all CKD subtypes. Conclusions: BMI-defined underweight and central obesity were independent risk factors for total CKD, and BMI and WC had different associations with risks for disease subtypes.

[Distribution and influencing factors of lipoprotein (a) levels in non-arteriosclerotic cardiovascular disease population in China].

Objective: To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors. Methods: This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels. Results: Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M (Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) (OR=1.23, 95%CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced (OR=0.68, 95%CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95%CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95%CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95%CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95%CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions: Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.

[Progress in research of relationship between marital status and cancer].

In recent 30 years, the global burden of cancer has become more serious, and one of social problem is population aging, plus declining birth rate, declining marriage rate and increasing divorce rate. Marriage is one of the most intimate and long-term social relations, and previous research had piecemeal reports of its impact on cancer morbidity and mortality without systematic review of evidence in high-quality population based epidemiological research. This paper summarizes the progress in research of the relationship between marital status and cancer to provide reference for future research and cancer prevention and control.

[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.

[Physical activity and its influencing factors in patients with diabetes mellitus: a comparative study between China and the United Kingdom].

Objective: To compare the differences in low-level physical activity (PA) and related influencing factors in patients with diabetes mellitus in China and the United Kingdom (UK). Methods: Using baseline survey data from the China Kadoorie Biobank and the UK Biobank, we analyzed the association between diabetes mellitus and low-level PA using logistic regression, with the participants' self-reported whether they had diabetes mellitus as the independent variable, and low-level PA as the dependent variable. Results: We included 509 254 Chinese adults and 359 763 British adults in the analysis. After adjusting for multiple factors, we found that both Chinese and British patients with diabetes mellitus were at elevated risk for low-level PA, with corresponding ORs (95%CIs) of 1.15 (1.12-1.19) and 1.37 (1.32-1.41), respectively. Patients with diabetes mellitus with longer disease duration and poorer glycemic control were at greater risk of having low-level of PA. Female, rural-distributed, employed, never-smoking Chinese diabetics, and male, urban-distributed, retired/unemployed, quit-smoking British diabetics were more likely to have low-level PA. Conclusions: Chinese and British patients with diabetes mellitus were more likely to have low-level PA compared with the general population, but the risk of low-level PA for patients in both countries varied by population characteristics. Therefore, PA guidelines and intervention measures should be based on the characteristics of individuals in the target countries and regions, which could improve PA levels among patients with diabetes mellitus.

[A prospective cohort study of factors associated with longevity in older adults in 10 areas of China].

Objective: To evaluate the associations of sociodemographic characteristics and lifestyle factors with longevity status in older adults in China. Methods: After excluding those born after 31st December 1938, a total of 51 870 older adults from the China Kadoorie Biobank (CKB) were included. The attained age was defined according to the survival age or age on 31st December 2018. According to the attained age, the old persons were categorized into non-longevity (died before age 80 years) and longevity (attained age ≥80 years). The longevity group was further divided into two groups: longevity with death occurring before 2019, and longevity and survival to 2019. The information about socio-demographic characteristics and lifestyles was collected at the 2004-2008 baseline survey. Multinomial logistic regression models were used to analyze the associations between exposure factors and outcomes by taking the non-longevity group as the reference group. Results: A total of 51 870 older adults aged 65-79 years in the baseline survey were included for analysis. During a follow-up for (10.2±3.5) years, 38 841 participants were longevity, and 30 354 participants still survived at the end of 2018. Compared to men, rural populations, non-married individuals, those with an annual household income of less than 10 000 yuan, and those with education levels of primary school or below, the adjusted ORs(95%CI) for longevity and survival to 2019 in women, urban residents, married individuals, those with annual household incomes ≥20 000 yuan, and those with education levels of college or university were 1.68 (1.58-1.78), 1.69 (1.61-1.78), 1.15 (1.10-1.21), 1.44 (1.36-1.53), and 1.32 (1.19-1.48), respectively. The OR (95%CI) for longevity and survival to 2019 was 1.09 (1.08-1.10) for those with an increase of 4 MET-hour/day in total physical activity level. With those who never or almost never smoked, had no alcohol drinking every week, had normal weight (BMI: 18.5-23.9 kg/m2), and WC <85 cm (man)/<80 cm (woman) as the reference groups, the ORs(95%CI) of longevity and survival to 2019 were 0.64 (0.60-0.69) for those smoking ≥20 cigarettes per day, 1.29 (1.14-1.46) for those with alcohol drinking every week, 1.13 (1.01-1.26) for those with pure alcohol drinking <30 g per day, 0.56 (0.52-0.61) for those being underweight, 1.27 (1.19-1.36) for those being overweight, 1.23 (1.11-1.36) for those with obesity, and 0.86 (0.79-0.93) for those with central obesity. Further stratified analysis by WC was performed. In the older adults with WC <85 cm (man)/<80 cm (woman), the ORs (95%CI) of longevity and survival was 1.80 (1.69-1.92) for those with each 5 kg/m2 increase in BMI and 1.02 (0.96-1.08) for those with WC ≥85 cm (man)/≥80 cm (woman). There was a statistically significant difference in the association between BMI and longevity between the two WC groups (interaction test P<0.001). Conclusion: This study showed that women, the married, those with higher socioeconomic status and education level, and those with healthy lifestyles were more likely to achieve longevity.

[Epidemiological distribution of mosaic loss of chromosome Y in adult men in 10 areas in China and its prospective association with lung cancer].

Objective: To detect the prevalence of mosaic loss of chromosome Y in adult men in ten study areas in China, describe the epidemiological distribution of mosaic loss of chromosome Y (mLOY) carriers and assess its prospective association with lung cancer. Methods: Based on the data from baseline survey, genetic analysis and follow-up (as of December 31, 2018) from China Kadoorie Biobank, we used Mosaic Chromosomal Alterations pipeline to detect mLOY carriers in 10 areas in China and described the epidemiological characteristics of mLOY carriers in adult men, including age, area distribution, lifestyle and disease history. We used multivariate logistic regression model to identify the potential relevant factor of mLOY. Cox proportional hazard regression model was fitted to assess the prospective association of mLOY with lung cancer. Stratification analysis were conducted to evaluate the potential modification effects of smoking and age. We also conducted mediation analysis to assess the mediating effect of mLOY in the association between smoking and lung cancer. Results: A total of 42 859 adult men were included in our analysis, in whom 2 458 mLOY carriers were detected (5.7%). The detection rate increased with age (P<0.05). The detection rate was higher in urban area (7.3%±0.2%) than that in rural area (4.7%±0.1%). The results of logistic regression analysis indicated that smoking might be a risk factor for the detection of mLOY (OR=1.49, 95%CI:1.36-1.64). After follow-up for average 11.1 years, 1 041 lung cancer cases were observed. The prospective analysis showed that mLOY carriers had an increased risk for lung cancer by 24% compared with non-mLOY carriers (HR=1.24, 95%CI:1.01-1.52) and expanded mLOY carriers (mLOY cell proportion ≥10%) had an increased risk for lung cancer by 50% (HR=1.50, 95%CI:1.13-2.00). Stratification analysis showed no modification effects of smoking and age in the association between mLOY and lung cancer (interaction P>0.05). Mediation analysis showed that mLOY could be a mediating factor in the association between smoking and lung cancer, the estimated effect was 0.09 (0.01-0.17). Conclusions: There were significant differences in the detection rate of mLOY in adult men with different social-economic characteristics and lifestyles in ten areas in China. Besides, mLOY carriers, especially expanded mLOY carriers, had increased risk for lung cancer and mLOY might be a mediating factor in the association between smoking and lung cancer.

[Comparative study on physical activity and its influencing factors in patients with chronic pulmonary obstructive disease between China and the United Kingdom].

Objective: To compare physical activity and its influencing factors in patients with chronic obstructive pulmonary disease (COPD) between China and the United Kingdom. Methods: We analyzed baseline data from China Kadoorie Biobank and the United Kingdom Biobank among COPD patients who were diagnosed with a one-second rate (FEV1/FVC) less than 70%. Physical activity level was calculated as metabolic equivalent (MET) and divided into three levels: low, medium, and high, according to tertiles stratified by gender and age. Multiple logistic regression was used to estimate ORs and 95%CIs for COPD and Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade about physical activity level, and subgroup analysis was conducted. Results: A total of 506 073 Chinese adults and 231 884 British adults were included. After adjusting for potential confounders, COPD was associated with lower physical activity levels in both Chinese and British COPD patients, with OR (95%CI) of 1.07(1.03-1.10) and 1.03(1.01-1.06) compared with non COPD patients, respectively. The GOLD grade was inversely correlated with physical activity level, particularly in a dose-response manner in the CKB population (trend test P<0.001). The negative relationship was stronger among the elderly, people with less education and lower economic status, and those with a smoking or chronic disease history. Chinese rural COPD patients were at high risk of decline of physical activity. Conclusions: Physical activity is inversely related to COPD, with a dose-response connection to GOLD grade. Therefore, physical activity maintenance and improvement should be encouraged and promoted in COPD patients, especially in high-risk groups.

Effects of different targeted therapies associated with adjuvant chemotherapy on clinical remission, survival and safety in patients with triple-negative breast cancer: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to systematically assess the effects of different targeted therapies associated with adjuvant chemotherapy on clinical remission, survival and safety of patients with triple-negative breast cancer (TNBC). MATERIALS AND METHODS: This study searched for case-control trials of TNBC patients from January 2010 to May 2022. Two researchers independently extracted data. RevMan 5.3 statistical software was used for analysis. RESULTS: This study included a total of 7 clinical controlled studies, containing 620 samples. The results showed that compared with the control group, the study group showed significant differences in objective response rate [OR = 2.44, 95% CI (1.69, 3.5), p < 0.00001], 1-year survival rate [OR = 3.59, 95% CI (2.01, 6.39), p < 0.0001], progression-free survival (PFS) [MD = 2.04, 95% CI (1.68, 2.41), p < 0.00001], with statistical significance (p < 0.05), while there are no significant differences in overall survival [MD = 6.33, 95% CI (-1.65, 14.30), p = 0.12] and incidence of adverse events [OR = 0.73, 95% CI (0.52, 1.02), p = 0.006] (p > 0.05). CONCLUSIONS: Targeted therapy associated with adjuvant chemotherapy can remarkably enhance the outcome of patients with advanced TNBC, prolonging their progression-free survival (PFS) and overall survival (OS) without increasing adverse effects. The validity of this research, however, will require higher quality studies and longer follow-ups.

[Epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration in adults from 10 regions of China].

Objective: To describe the epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration (mCA) in community adults aged 30-79 years in 10 regions of China. Methods: A total of 100 297 participants with complete baseline information (demographic characteristics, lifestyle, physical examination, etc.) and genotyping data of blood-derived DNA in ten regions of the China Kadoorie Biobank study were included. The mCAs were detected with the Mosaic Chromosomal Alterations pipeline, and logistic regression models were used to compare the differences in the detection rate of mCAs in different regions and populations. Results: A total of 5 810 mCA carriers were detected, with the detection rate of 5.8%. The standardized detection rate was 5.1%. The baseline detection rate of mCA increased with age, which were 3.4%, 5.0%, and 9.4% in those aged 30-, 51-, and >60 years, respectively (trend test P<0.001). A more significant proportion of mCAs were found in men (8.0%) than women (4.0%), as well as in urban areas (6.4%) than in rural areas (5.3%), the difference was significant (P<0.001). After adjusting for age and gender, the detection rate of mCA was higher in current smokers or people quitting smoking due to illness and people with low physical activity level, and the mCA detection rate was lower in obesy people (5.3%) than that in people with normal body weight (5.9%) (P=0.006). Conclusions: The detection rate of mCAs varied with region and population in community adults aged 30-79 years in 10 regions of China. The study results might contribute to the molecular identification of aging populations and guide precision prevention of age-related diseases such as cancers.

[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.

[Progress on genome-wide association studies on mosaic chromosomal alterations].

Mosaic chromosomal alteration (mCA) is referred to as large-scale somatic mutations on chromosomes, which results in diverse karyotypes in body. The mCA is regarded as one of the phenotypes of aging. Studies have revealed its associations with many chronic diseases such as hematopoietic cancers and cardiovascular diseases, but its genetic basis (e.g. genetic susceptibility variants) is still under-investigated. This paper reviews GWAS studies for mCA on autosomal chromosomes and sex chromosomes [mosaic loss of the Y chromosome (mLOY) and mosaic loss of the X chromosome (mLOX)] based on large population, respectively. Most of the genetic susceptibility loci found in studies for autosomal mCA were associated with copy-neutral loss of heterozygosity. The study of sex chromosome mCA focused on mosaic loss mutations. The number of genetic susceptibility loci for mLOY was high (up to 156), but it was relatively less for mLOX.

Modeling functional network topology following stroke through graph theory: functional reorganization and motor recovery prediction

The study of functional reorganization following stroke has been steadily growing supported by advances in neuroimaging techniques, such as functional magnetic resonance imaging (fMRI). Concomitantly, graph theory has been increasingly employed in neuroscience to model the brain's functional connectivity (FC) and to investigate it in a variety of contexts. The aims of this study were: 1) to investigate the reorganization of network topology in the ipsilesional (IL) and contralesional (CL) hemispheres of stroke patients with (motor stroke group) and without (control stroke group) motor impairment, and 2) to predict motor recovery through the relationship between local topological variations of the functional network and increased motor function. We modeled the brain's FC as a graph using fMRI data, and we characterized its interactions with the following graph metrics: degree, clustering coefficient, characteristic path length, and betweenness centrality (BC). For both patient groups, BC yielded the largest variations between the two analyzed time points, especially in the motor stroke group. This group presented significant correlations (P<0.05) between average BC changes and the improvements in upper-extremity Fugl-Meyer (UE-FM) scores at the primary sensorimotor cortex and the supplementary motor area for the CL hemisphere. These regions participate in processes related to the selection, planning, and execution of movement. Generally, higher increases in average BC over these areas were related to larger improvements in UE-FM assessment. Although the sample was small, these results suggest the possibility of using BC as an indication of brain plasticity mechanisms following stroke.

[Mediating effect of physical activity on association between sedentary leisure-time and obesity indexes among hypertensive individuals].

Objective: To explore the mediating effect of physical activity on association between sedentary leisure-time and obesity indexes among hypertensive individuals. Methods: After excluding of those with a prior history of heart disease, stroke and cancer, a total of 20 178 hypertensive participants in the China Kadooire Biobank (CKB) study from Wuzhong district of Suzhou city were included. Mediating effect analysis was used to analyze the mediating effect of physical activity (PA) on correlation between sedentary leisure-time and body fat percentage (BFP), waist circumference (WC) and body mass index (BMI). Results: After adjusted for age, gender, smoking status, alcohol consumption, education levels, intake frequencies of meat and intake frequencies of fresh fruit, sedentary leisure-time (SLT) was negatively correlated with PA (ß=-0.246, P<0.001), but positively associated with BFP (ß=0.061, P<0.001), WC (ß=0.087, P<0.001) and BMI (ß=0.071, P<0.001). After including the mediator variable PA, the direct effect of SLT on obesity index was still significant. PA was negatively correlated with BFP, WC and BMI (ß=-0.052, -0.083 and -0.028, respectively, P<0.001). Analysis of mediating effect indicated that the association of SLT with BFP, WC and BMI were partly mediated by PA, the proportion of mediating effect was 20.820%, 23.421% and 9.915%. Stratified by gender, PA had mediating effect on SLT and all obesity indexes in women, while only on SLT and BFP and WC in men. Conclusions: There is a significant mediating effect of PA on correlation between SLT and obesity indexes among hypertensive individuals. Hypertensive patients should increase the level of physical activity and reduce sedentary behavior to achieve a profounder healthy effect.

[Polygenic risk score in personalized screening of lung cancer: a prospective cohort study in Chinese].

Objective: To explore how to personalize lung cancer screening programs for prevention in Chinese populations based on individual genetic risk score. Methods: We constructed the lung cancer polygenic genetic risk score (PRS-19) based on the 19 previously published genetic variations, using 100 615 participants with genotyping data from the China Kadoorie Biobank (CKB). Using the 5-year absolute risk of lung cancer in a population (55 years old with at least 30-pack-year history of smoking) as reference, the trend of 5-year absolute risk in different genetic risk groups was calculated in smokers and non-smokers, respectively. Distribution curves of 5-year absolute risk were also described to determine the theoretical age or smoking dose when different genetic risk groups reached the reference values. Given the overall findings, the specific start age for lung cancer screening were suggested for different genetic risk groups. Results: The 5-year absolute risk of lung cancer was 0.67% in 55-year-old smokers with 30 packs per year in the CKB. Among smokers, 5-year absolute risk of participants increased as the genetic risk increased. Hence, it was recommended that people at high genetic risk should start screening earlier. For the highest genetic risk populations (the top 1% of PRS), the start age might be changed to 50 years old. If the start age remained at 55-year-old, the smoking dose should be set lowered in high genetic risk populations. For the highest genetic risk populations, they should be included in lung cancer screening regardless of the cumulative smoking exposure. Among nonsmokers, it was also valuable to screen people with high genetic risk, considering the start age of 62 for the highest genetic risk populations and 74 for the lowest genetic risk populations (the bottom 5% of PRS). Conclusions: PRS-19 can be effectively used in developing lung cancer screening program for individualized prevention in China. For smokers with high genetic risk, the recommended starting age and smoking dose could be lowered for lung cancer screening, and non-smokers with high genetic risk could also be included in the screening programs.

[Prevalence of heart failure and its association with smoking behavior in adults from 10 regions of China].

Objective: To describe the prevalence of heart failure in China and to explore the prospective association between smoking behavior and the risk of incident heart failure. Methods: The subjects were from the China Kadoorie Biobank (CKB) and the baseline survey was conducted from June 2004 to July 2008. A total of 487 197 subjects were included in this study, after excluding those with missing BMI information, lost follow-up immediately after baseline investigation, and self-reported coronary heart disease, stroke, or malignant tumor at baseline. This study included data from baseline and follow-up until December 31, 2016. Cox proportional hazards regression models were used to estimate the association between smoking behavior and the risk of heart failure. Results: The median follow-up time was 10.15 years, during which a total of 4 208 new cases of heart failure occurred, with a crude incidence rate of 0.87/1 000 person-years and a cumulative incidence rate of 0.86%. The higher the age at baseline, the higher the incidence of heart failure. The incidence of heart failure in high age group, rural area and male was higher than that in low age group, urban area and female population respectively. Compared with non-smokers, there was no significant difference in the risk of heart failure in occasional smokers (HR=1.05; 95%CI: 0.91-1.22), while former smokers (HR=1.48; 95%CI:1.31-1.67) and current smokers (HR=1.34;95%CI:1.22-1.49) increased risk. Former smokers (HR=1.33;95%CI:1.21-1.46) and current smokers (HR=1.46; 95%CI:1.31-1.64) had higher risk of heart failure than non-smokers or occasional smokers. No dose-response relationship was observed between the number of cigarettes smoked per day and the risk of heart failure in current and former smokers (for trend P=0.347 and 0.066). Compared with non-smokers or occasional smokers, the hazard ratios of <5, 5-, 10- and ≥20 years since quit smoking were 1.61 (95%CI: 1.36-1.92), 1.55 (95%CI: 1.27-1.90), 1.24 (95%CI: 1.02-1.51) and 1.35 (95%CI: 1.08-1.68), respectively (for trend P=0.091). The hazard ratios of quitting smoking due to disease and other reasons were 1.62 (95%CI:1.41-1.86) and 1.23 (95%CI: 1.04-1.45). Healthy smoking behaviors had a significant protective effect on heart failure compared with non-healthy smoking behaviors (HR=0.75, 95%CI:0.69-0.81). Area and family history of coronary heart disease, and the smoking behaviors interacted with the risk of heart failure (for all interactions were P<0.05). Conclusions: The incidence of heart failure in China is higher in males than females, higher in rural areas than in urban areas, and increases with age. Both former smokers and current smokers had a higher risk of heart failure than nonsmokers or occasional smokers, regardless of the frequency, amount, duration, and reason for quitting. Smoking is an important risk factor for heart failure and comprehensive anti-smoking measures should be maintained.

[Characteristics of human papillomavirus infection and abnormal cervical cytology in health check-up females in Shenzhen].

Objective: To describe the characteristics of human papillomavirus infection and thinprep cytologic test (TCT) outcome in health check-up females in Shenzhen. Methods: Use cross-sectional design, collect information from data from health check-up females in Shenzhen and describe characteristics of HPV infections screening and TCT outcomes. Results: We collected the data of 75 754 females, 103 508 females and 69 964 females received HPV detection, TCT and combined detection respectively. HPV standardized infection rate was 19.89% (95%CI: 19.45%-20.33%) and showed a "U-shaped" pattern in age distribution. The most prevalent HPV genotypes were 52, 51, 16, 58 and 53. Infection rate was higher for high-risk HPV than low-risk HPV genotype. Single infection was more common than its multiple infection. In addition, 7.48% (95%CI: 7.22%-7.75%) women were TCT positive, of whom 4.58% (95%CI: 4.40%-4.76%), 2.54% (2.40%-2.69%), 0.27% (95%CI: 0.23%-0.31%) had atypical squamous cells, low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, respectively. Overall and subtype HPV infection rates increased with severity of abnormal cervical cytology. The most prevalent HPV genotypes were 52, 58 and 16 in women with abnormal cervical cytology. Conclusions: HPV prevalence remains at a high level in Shenzhen. This study suggests that attention should be paid to HPV screening, especially in young, perimenopausal women and in high risk HPV genotype infection. Timely follow-up and cervical cytology screening are required for women with high-risk HPV infection or persistent infection. Future vaccination strategies should take account of prevalent HPV genotype.

[Transitions on frailty status and related risk factors for its status worsening: finding from the Beijing MJ Health Screening Center].

Objective: To evaluate the transitions of frailty status and related factors influencing its worsening in middle-aged and elderly adults. Methods: Data was obtained from the Beijing MJ Health Screening Center. A total of 13 689 participants who attended health checkups at least twice during 2008-2019 and had more than three years' intervals during these two health checkups were included in the study. The frailty index comprising 28 variables was used to measure frailty status. Frailty was defined as frailty index ≥0.25, and prefrailty was defined as frailty index >0.10 and <0.25. Logistic regression analysis was performed to investigate the association of socio-demographic factors and lifestyle characteristics with the worsening of frailty status, stratified by frailty status at the first health checkup. Results: The mean age at the first and last health checkups were (42.3±9.2) and (47.9±9.3) years, respectively. The mean interval during these two health checkups was (5.7±1.9) years. At the first health checkup, the prevalence of frailty and prefrailty were 2.5% and 50.3%, respectively. While at the last health checkup, the prevalence of frailty and prefrailty rose to 3.9% and 55.4%. Of all participants, 67.3% remained in the same frailty state, 21.2% worsening, and 12.5% improving. In robust participants at the first health checkup, older age, female, low education level, smoking cessation, daily smoking, being general obesity measured by BMI or central obesity measured by WHR showed an increased the risk of worsening frailty status. However, in prefrail participants at the first health checkup, older age, female, general, or central obesity presented as risk factors for worsening frailty status. Conclusion: Modifiable factors such as low education level, smoking, and obesity may increase the risk of worsening frailty status.

DUXAP8 promotes the proliferation and migration of ovarian cancer cells via down-regulating microRNA-29a-3p expression.

OBJECTIVE: To study the role of long-chain non-coding RNA (lncRNA) DUXAP8 in ovarian cancer (OCa) and the underlying potential mechanism. PATIENTS AND METHODS: The expression pattern of DUXAP8 in ovarian cancer was analyzed using the GEPIA database. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the expression of DUXAP8 in OCa tissues; at the same time, OCa cell lines were cultured to complete functional experiments, including cell counting kit-8 (CCK-8), plate cloning experiments and transwell experiments to evaluate the effects of DUXAP8 on the proliferative and migration ability of OCa cell lines. Bioinformatics analysis and Dual-Luciferase reporter genes were used to determine the binding and expression of DUXAP8 to its downstream key gene microRNA-29a-3p in OCa cells. In addition, co-transfection technology and cell function recovery experiments were used to verify the important role of the DUXAP8/microRNA-29a-3p regulatory network in OCa. RESULTS: DUXAP8 was abnormally highly up-regulated in OCa tissues and cell lines, besides, its expression was related to poor prognosis of patients. CCK-8 and plate cloning experiments showed that knockdown of DUXAP8 in OCa cells can significantly inhibit the proliferation of OCa cells. Transwell results suggested that knockdown of DUXAP8 can significantly inhibit OCa cell migration. In addition, it was found that DUXAP8 can bind and negatively regulate the expression of microRNA-29a-3p in OCa. Functional experiments in OCa cells also revealed that microRNA-29a-3p was a key downstream gene that mediated the regulation of DUXAP8 on OCa function. CONCLUSIONS: DUXAP8 has abnormally high expression in OCa and can lead to malignant progression of the tumor.

[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.