[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.

[Recurrent hemoptysis after aorta aneurysm stent implantation: a case report].

The etiology of hemoptysis is diverse and complex, with aorta aneurysm being identified as a rare cause of cryptogenic hemoptysis. Here, we reported a 56-year-old male patient who experienced hemoptysis due to a thoracic aorta aneurysm that persisted despite stent implantation. Further investigation revealed the presence of a lateral thoracic artery-pulmonary artery fistula and an aortobronchial fistula, diagnosed by angiography and multidisciplinary consultation. Therefore, patients with recurrent hemoptysis after aortic surgery should be monitored for the possibility of an aortobronchial fistula.

[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.

[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.

[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.

[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.

The prognosis value of proteasome activator subunit 3 expression in gastric cancer.

Gastric cancer (GC) is a highly aggressive malignant tumor, and, therefore, the prognosis evaluation of this disease is important. Proteasome activator subunit 3 (PSME3) is highly expressed in GC; however, its exact role in GC has yet to be clarified. The gene expression profiles for GC were downloaded to find a candidate prognostic biomarker, and PSME3 was selected. The expression level of the PSME3 gene in GC tissues was analyzed using a public database. The biological processes and signal pathways that PSME3 was involved in were further analyzed. Immunohistochemical staining of 181 GC tissues was performed to detect the expression of the PSME3 protein. The correlation between PSME3 expression and GC prognosis and its clinical and pathological parameters were investigated. It was found that PSME3 mRNA expression was higher in GC than in adjacent gastric tissues, and high PSME3 expression was significantly correlated with tumor stage, histological subtype, lymph node metastasis status, and Helicobacter pylori infection in patients with GC (all p<0.01). Bioinformatics showed that PSME3 mainly played an oncogenic role in the development of GC by regulating the cell cycle and inhibiting apoptosis. The PSME3 protein was overexpressed in 64.6% (117/181) of the analyzed samples, and overexpression of PSME3 was associated with a significantly poor prognosis. In addition, multivariate analysis suggested that PSME3 overexpression, tumor, node, metastasis stage, and tumor size are independent prognostic biomarkers for GC. We conclude that the overexpression of PSME3 was associated with a poor prognosis in patients with GC, and PSME3 might play an oncogenic role in the occurrence and development of GC.

[Associations between sleep status and risk for kidney stones in Chinese adults: a prospective cohort study].

Objective: To analyze the associations between sleep status and the risk for kidney stone in Chinese adults. Methods: This study used baseline and long-term follow-up data of China Kadoorie Biobank. After excluding those with self-reporting of diagnosed chronic kidney disease and cancer and those with extreme values of sleep duration at baseline survey, 501 701 participants were included in this study. The information about their sleep status were collected, including insomnia symptoms, daytime sleepiness, nap habit, snoring and sleep duration. The sleep score was constructed based on insomnia symptoms, daytime sleepiness, and sleep duration, ranging from 0 to 3. Cox proportional hazards regression models were used to evaluate the association of sleep status with the risk for kidney stone, including individual sleep factors and combined sleep score. Results: During the follow-up for average (10.7±2.2) years, 12 381 cases of kidney stone were recorded for the first time. Compared with participants without insomnia symptoms, the multivariable-adjusted HR of kidney stone in those with difficulty falling asleep and waking up early were 1.12 (95%CI: 1.06-1.18) and 1.06 (95%CI: 1.00-1.12), respectively. There was no statistically significant association of kidney stone risk with sleeping pill use, daytime sleepiness, nap habit, or snoring. Compared with participants with sleep duration ≥7 hours per day, the HR of kidney stone in those with sleep duration <7 hours per day was 1.13 (95%CI: 1.08-1.18). Compared with participants with sleep score of 3 (highest sleep quality), the HR of kidney stone in those with sleep score of 2, 1, and 0 were 1.08 (95%CI: 1.03-1.13), 1.16 (95%CI: 1.10-1.23), and 1.19 (95%CI: 1.03-1.37), respectively. Conclusion: In China, adults with insomnia symptoms or short sleep duration have increased risk for kidney stone.

[A prospective cohort study of premature death and influencing factors in adults aged 56-69 years from 10 regions of China].

Objective: To describe and analyze the epidemiological characteristics of premature death (death before age of 70 years) and related risk factors in approximate 100 000 adults recruited from 10 regions of China during a 10-year follow-up. Methods: Data, including demographic characteristics, lifestyle and physical indicators as well as health outcomes as of December 31, 2017, were obtained from baseline survey and long-term follow-up of the China Kadoorie Biobank (CKB) study. All-cause and cause-specific premature death in different areas, in men and women and in people with different lifestyles were analyzed. Cox proportional risk model was used to analyze the associations between baseline factors and premature death. Results: A total of 99 993 participants aged 56-69 years were included in the study. During 10 years of follow-up, 7 530 premature deaths were recorded and the premature death rate was 7.15 per 1 000 person-years. The main causes of premature death were cancer and cardiovascular and cerebrovascular diseases. The premature mortality rate was higher in rural areas, in northern region and in men, and decreased with age (P<0.05). Premature death was more likely to occur in smokers, and a dose-response relationship was observed. Compared with non-drinkers, the risk for premature death was higher in ex-drinkers (HR: 1.25 [95%CI:1.16-1.36]) and heavy drinkers (average alcohol consumption ≥60 g/d) (HR: 1.20 [95%CI:1.08-1.34]). The risk for premature death decreased with the increase of physical activity. Low body weight and central obesity were independently associated with increased risk for premature death (HR: 1.67 [95%CI:1.55-1.81] and 1.13 [95%CI:1.05-1.21], respectively). Conclusions: The main causes of premature death in adults aged 56-69 years in China during 10-year follow-up were cancer and cardiovascular and cerebrovascular diseases. The premature mortality rate varied with socioeconomic and demographic characteristics. The risk for premature death was influenced by multi factors, such as lifestyle and physical conditions.

[Association of lifestyle and cardiometabolic risk factors with epigenetic age acceleration in adults in China].

Objective: To explore the association of lifestyle and cardiometabolic risk factors with five epigenetic age acceleration (AA) indices. Methods: This study included 980 participants of China Kadoorie Biobank, for whom genome-wide DNA methylation of peripheral blood cells had been detected in baseline survey. Five indices of DNA methylation age (DNAm age) were calculated, i.e. Horvath clock, Hannum clock, DNAm PhenoAge, GrimAge and Li clock. Epigenetic AA was defined as the residual of regressing DNAm age on chronological age. Lifestyle factors studied included smoking status, alcohol consumption, eating habits, physical activity level and body shape defined by a combination of BMI and waist circumference. Cardiometabolic risk factors included blood pressure, blood glucose level and total cholesterol level. Linear regression model was used to analyze the association of lifestyle and cardiometabolic risk factors with AA (ß). Results: GrimAge_AA was associated with smoking status, alcohol consumption, physical activity level and BMI. Compared with non-smokers, non-drinkers, or participants with BMI of 18.5- 23.9 kg/m2, the smokers who smoked 1-14 cigarettes/day (ß=0.71, 95%CI: 0.57-0.86), 15-24 cigarettes/day (ß=0.88, 95%CI: 0.73-1.03), and ≥25 cigarettes/day (ß=0.99, 95%CI: 0.81-1.18), respectively, heavy drinkers with daily pure alcohol consumption ≥60 g (ß=0.33, 95%CI: 0.11-0.55) and participants with BMI<18.5 kg/m2 (ß=0.23, 95%CI: 0.03-0.43) showed accelerated aging. Compared with those in the lowest quintile of physical activity level, participants in the top three quintile of physical activity level showed decelerated aging (ß=-0.13, 95%CI: -0.26-0.01, ß=-0.12, 95%CI: -0.26-0.02, and ß=-0.14, 95%CI: -0.27- -0.00, respectively). GrimAge_AA decreased with the increase of the number of healthy lifestyle factors (P<0.001). Compared with the participants with 0 to 1 healthy lifestyle factor, the ß of those with 2, 3, or 4 to 5 healthy lifestyle factors were -0.30 (95%CI: -0.47- -0.12), -0.47 (95%CI: -0.65- -0.30) and -0.72 (95%CI: -0.90- -0.53), respectively. The other four indices were not statistically significantly associated with most lifestyle factors. None of the five indices of AA was associated with blood pressure, blood glucose level or total cholesterol level. Conclusion: People with unhealthy lifestyle showed accelerated epigenetic aging, that is, the predicted DNAm age is older than their own chronological age.

[Association between genetic predisposition to childhood obesity and the risk of adult ischemic heart disease in China].

Objective: To examine the associations of childhood obesity, assessed by genetic variations of childhood body mass index (BMI), with the risk of adult ischemic heart disease (IHD) and major coronary event (MCE). Methods: More than 69 000 participants from the China Kadoorie Biobank were genotyped. After excluding those with coronary heart disease, stroke, or cancer at baseline, a total of 64 454 participants were included in this study. Based on genome-wide significant single nucleotide polymorphisms (SNPs), childhood BMI genetic risk score were constructed for every participant and divided into quintiles, with the lowest quintile as the low genetic risk group and the highest quintile as the high genetic risk group. Cox proportional hazards regression models were used to estimate the association between genetic predisposition to childhood obesity and the risk of ischemic heart disease. Results: During a median of 10.7 years of follow-up, 7 073 incident cases of IHD and 1 845 cases of MCE were documented. After adjusting for sex, age, region, and the first ten genetic principal components, the HRs (95%CIs) for IHD and MCE in the high genetic risk group were 1.10 (1.02-1.18) and 1.10 (0.95-1.27), compared with the low genetic risk group. IHD risk increased by 4% (2%-6%) for each one standard deviation increase in genetic risk score (trend P=0.001). After further adjustment for baseline BMI, the differences between genetic risk groups were not statistically significant, but there was still a linear trend between genetic risk score and IHD risk (trend P=0.019). Conclusions: IHD risk increased with genetic predisposition to childhood obesity, suggesting that childhood obesity is an important risk factor for the development of IHD in China. As an easily identifiable feature, changes of childhood BMI should be monitored regularly to realize early intervention of IHD in adults.

[Association between tea consumption and all-cause mortality in Chinese adults].

Objective: To investigate the association between tea consumption and the risk of all-cause and cause-specific mortality among Chinese adults. Methods: This study was based on China Kadoorie Biobank (CKB). Tea consumption information was self-reported by participants at baseline. Death was mainly identified by linkage to the death registry system. Cox proportional hazard regression models estimated HR and 95%CI. Results: With a median follow-up of 11.1 years, there were 34 661 deaths in 438 443 participants. Compared with those who never drink tea, all-cause mortality HR(95%CI) were 0.89(0.86-0.91) and 0.92(0.88-0.95) for non-daily tea drinkers and daily tea drinkers, respectively. A statistically significant difference was found in the association of tea consumption and the risk of all-cause mortality between men and women(interaction P<0.05). The protective effect was mainly seen in men. Compared with those who never drink tea, daily tea drinkers had a reduced risk of death from ischemic heart disease, ischemic stroke, hemorrhagic stroke, cancer, respiration diseases and other causes of death, and the corresponding HR(95%CI) were 0.83(0.76-0.92), 0.82(0.69-0.97), 0.86(0.78-0.94), 1.03(0.97-1.09), 1.00(0.87-1.16), 0.84(0.78-0.90). Among never smokers and non-excessive drinkers, there was no statistically significant association between daily tea drinking and the risk of death from cancer. While smokers and excessive drinkers had an increased risk of death from cancer (interaction P<0.001). Conclusions: Tea consumers had reduced risks of all-cause mortality and partial cause-specific mortality, but not for the risk of death from cancer. On the contrary, daily tea drinkers with smoking habits and excessive alcohol drinking had an increased risk of death from cancer.

[Associations of body mass index and waist circumference with hospitalization risk of kidney stones in Chinese adults].

Objective: To evaluate the associations of body mass index (BMI) and waist circumference with hospitalization risk of kidney stones in Chinese adults. Methods: This study used long-term follow-up data from China Kadoorie Biobank. After excluding participants with chronic kidney disease, cancer, and extreme BMI or waist circumference values at baseline, 502 096 participants were included in the present analysis. Cox proportional hazards regression models were used to estimate the associations of BMI and waist circumference with hospitalization risk of kidney stones. Results: During an average follow-up period of (10.7±2.2) years, 12 396 participants were hospitalized for the first time with kidney stones. Using the participants with BMI (kg/m2) of 20.5-22.4 as reference, the multivariable-adjusted HR (95%CI) for those with BMI of <18.5, 18.5-20.4, 22.5-23.9, 24.0-25.9, 26.0-27.9, 28.0-29.9, and ≥30.0 were 0.96 (0.87-1.05), 0.94 (0.88-1.00), 1.11 (1.05-1.17), 1.25 (1.18-1.32), 1.29 (1.21-1.37), 1.39 (1.28-1.50), and 1.54 (1.40-1.71), respectively. For every 1 kg/m2 increase in BMI, the HR of kidney stones hospitalization increased by 4% (HR=1.04, 95%CI: 1.04-1.05). Using the participants with waist circumference (cm) of 75.0-79.9 as reference, the multivariable-adjusted HR (95%CI) for those with waist circumference of <65.0, 65.0-69.9, 70.0-74.9, 80.0-84.9, 85.0-89.9, 90.0-94.9, and ≥95.0 were 0.82 (0.74-0.91), 0.85 (0.80-0.92), 0.95 (0.89-1.00), 1.16 (1.09-1.22), 1.22 (1.15-1.30), 1.28 (1.19-1.38), and 1.46 (1.35-1.58), respectively. For every 5 cm increase in waist circumference, the HR of kidney stones hospitalization increased by 9% (HR=1.09, 95%CI: 1.08-1.10). After mutually adjusting for BMI and waist circumference in the above models, the association between BMI and hospitalization risk of kidney stones disappeared. In contrast, the association between waist circumference and hospitalization risk of kidney stones remained unchanged. Conclusions: BMI and waist circumference were positively associated with hospitalization risk of kidney stones. The increased waist circumference was an independent risk factor for kidney stones among Chinese adults.

[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.

[Studies on efficacy of a bioabsorbable steroid-eluting sinus stent in the frontal sinus opening of chronic rhinosinusitis with nasal polyps].

Objective: To assess the efficacy of a bioabsorbable steroid-eluting sinus stent in improving surgical outcomes when placed in the frontal sinus ostium (FSO) following full endoscopic sinus surgery (ESS) in patients with whole group chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients with whole group CRSwNP who had similar lesions on bilateral sinus between September 2019 and March 2020 in Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Changhai Hospital were chosen. Patients with CRSwNP who underwent extended ESS were randomly assigned to receive a steroid-eluting sinus stent in one FSO whereas the contralateral side received surgery alone. Endoscopic evaluations recorded at 30, 90 days postoperative were graded by an independent assessment panel to assess the need for interventions in the FSO. Semi-quantitative data with CT and endoscopic score were performed by rank sum test. The need for postoperative intervention and the patency rate of FSO were analyzed using the McNemar test. Results: Thirty-one patients with whole group CRSwNP met all eligible criteria, including 17 males and 14 females, with the age of (44.5±11.8) years(x¯±s). Stents were successfully placed in one FSO of all patients. At 30 days post-ESS, the assessment panel reported that steroid-eluting stents reduced the need for postoperative interventions by 41.0% (χ2=5.314,P=0.021), the need for oral steroid interventions by 40.0% (χ2=4.133,P=0.042) and the need for surgical interventions by 74.8% (χ2=4.292,P=0.038) compared to control sinuses with no stents. Clinical surgeons also reported greater diameter of FSO compared to control sinuses at 30 days post-ESS (74.2% vs 48.4%, χ2=4.351, P=0.037). These results at 90 days post-ESS were consistent with those at 30 days post-ESS. Conclusion: Bioabsorbable steroid-eluting sinus stents in the FSO can reduce polyp formation, adhesion, and the need for postoperative interventions in FSO of CRSwNP patients and improve the early postoperative outcomes.

[A multicenter retrospective study on the etiology of necrotizing pneumonia in children].

Objective: To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China. Methods: A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ2 test was used for categorical variables. Results: A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ2=6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ²=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ2=4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×109/L vs. 10.5 (2.5-32.2)×109/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) µg/L vs. 0.24 (0.01-18.85) µg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions: The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.