Inverted U-Shaped Association of Plasma Resolvin D2 With Atherosclerotic Cardiovascular Disease and the Mediation Effects of Serum Cholesterol: A Chinese Community-Based Study.

BACKGROUND: Resolvin D2 (RvD2) has been reported to protect against the development of atherosclerosis in animal models. The objective of this study was to examine the prospective association between plasma RvD2 and the risk of atherosclerotic cardiovascular disease (ASCVD) at the population level. METHODS AND RESULTS: A cohort of 2633 community-dwelling individuals aged 35-60 years was followed for 8 years in this study. Adjusted hazard ratios and 95% CIs for ASCVD outcomes according to baseline RvD2 levels were calculated using Cox proportional hazards models. Mediation analysis was used to test the indirect effect of serum cholesterol indicators on the association between RvD2 and ASCVD probability. In total, 284 new cases of ASCVD were identified during follow-up. An inverted U-shaped association between natural log (ln)-transformed RvD2 and incident ASCVD was determined, and the threshold value for lnRvD2 was 3.87. Below the threshold, each unit increase in lnRvD2 was associated with a 2.05-fold increased risk of ASCVD (95% CI, 1.13-3.74; P=0.019). Above the threshold, each unit increase in lnRvD2 was associated with a 36% reduced risk of ASCVD (95% CI, 0.51-0.80; P<0.001). In addition, the association between RvD2 and ASCVD probability was partially mediated by high-density lipoprotein cholesterol (15.81%) when lnRvD2 <3.87, but by total cholesterol (30.23%) and low-density lipoprotein cholesterol (30.13%) when lnRvD2 ≥3.87. CONCLUSIONS: Both lower and higher RvD2 levels are associated with a reduced risk of ASCVD, forming an inverted U-shaped relationship. Furthermore, this association is partially mediated by total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol.

Green tea consumption and incidence of cardiovascular disease in type 2 diabetic patients with overweight/obesity: a community-based cohort study.

BACKGROUND: Green tea has been reported to be potentially protective against the development of cardiovascular disease (CVD). This study aimed to investigate the association between green tea consumption and incident CVD in type 2 diabetes (T2D) patients with overweight/obesity. METHODS: A total of 4756 Chinese overweight/obese T2D patients were recruited and followed up for 6.27 years. Information on green tea consumption was collected at baseline using interviewer-administered questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD according to green tea consumption were estimated using the Cox proportional hazards model. RESULTS: Compared with non-habitual consumers, participants who consumed > 5 g/day of green tea leaves reduced the risk of CVD by 29% (95%CI: 0.55-0.92), stroke by 30% (95%CI: 0.51-0.95) and coronary heart disease (CHD) by 40% (95%CI: 0.40-0.89). Similarly, participants who consumed green tea for ≥ 40 years reduced the risk of CVD by 31% (95%CI: 0.54-0.88), stroke by 33% (95%CI: 0.50-0.90) and CHD by 39% (95%CI: 0.42-0.88). Among participants with < 5-year history of T2D, > 5 g/day of tea leaves and > 40 years of tea consumption were associated with 59% (95%CI: 0.23-0.72) and 57% (95%CI: 0.26-0.74) reduced risk of stroke, respectively. However, among participants with ≥ 5-year history of T2D, > 5 g/day of tea leaves and > 40 years of tea consumption were associated with a 50% (95%CI: 0.30-0.82) and 46% (95%CI: 0.35-0.85) reduced risk of CHD, respectively. CONCLUSIONS: Green tea consumption is associated with reduced risk of CVD, stroke, and CHD in overweight/obese T2D patients.

Trimethylamine N-oxide, ß-alanine, tryptophan index, and vitamin B6-related dietary patterns in association with stroke risk.

BACKGROUND AND AIMS: The aim of this study was to examine the associations of dietary patterns derived by reduced-rank regression (RRR) model reflecting variation in novel biomarkers (trimethylamine N-oxide, ß-alanine, tryptophan index, and vitamin B6) with stroke risk. METHODS AND RESULTS: We performed analyses based on a community-based cohort study "the Prospective Follow-up Study on Cardiovascular Morbidity and Mortality in China (PFS-CMMC)". Factor loadings were calculated by RRR using 11 food groups collected via a validated food frequency questionnaire and the four response variables based on its nested case-control data (393 cases of stroke vs. 393 matched controls). Dietary pattern scores were derived by applying the factor loadings to the food groups in the entire cohort (n = 15,518). The associations of dietary pattern with the stroke risk were assessed using Cox proportional hazards models. The dietary pattern characterized with higher intakes of red meat and poultry but lower intakes of fresh vegetables, fresh fruits, and fish/seafoods were identified for further analyses. The hazard ratios (HR) for the highest vs. lowest quartile was 1.55 [95 % confidence interval (CI): 1.18-2.03, P trend = 0.001] for total stroke, 2.96 [95 % CI: 1.53-5.71, P trend <0.001] for non-ischemic stroke, after adjustment for sex, age, educational attainment, current smoking, current drinking, body mass index, total energy intake, family history of stroke, hypertension, diabetes, hyperlipidemia, and estimated glomerular filtration rate. CONCLUSION: Our findings highlight the importance of limited meat intake and increased intakes of fresh vegetables, fruits, and fish/seafoods in the prevention of stroke among Chinese adults.

Association between chemotherapy-induced myelosuppression and curative efficacy of 2-cycle chemotherapy in small cell lung cancer.

BACKGROUND: The association of chemotherapy-induced myelosuppression with tumor response and overall survival remained controversial. The study was conducted to investigate the association between them in small cell lung cancer (SCLC). METHODS: 204 eligible patients with SCLC were respectively included and categorized into three groups (no, mild, and severe myelosuppression) based on myelosuppression degree after the first chemotherapy. Curative efficacy of 2-cycle chemotherapy was evaluated by the objective response rate (ORR) and disease control rate (DCR). Univariate and multivariate logistic regression analyses were conducted to investigate their association. Receiver operator characteristic (ROC) curves, net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to assess the predictive ability of myelosuppression. RESULTS: In the fully-adjusted model, mild (OR, 4.61; 95% CI, 1.35 to 18.27; P = 0.020) and severe (OR, 7.22; 95% CI, 1.30 to 72.44; P = 0.046) myelosuppression were positively associated with DCR. However, only mild myelosuppression was significantly associated with ORR (OR, 2.78; 95% CI, 1.30 to 6.14; P = 0.010). Although we observed evidence of increased ORR in severe myelosuppression, the difference was not statistically significant. Furthermore, based on the results of the ROC curve, NRI and IDI, chemotherapy-induced myelosuppression cannot be used as a accurate and independent predictor for curative efficacy, but it can improve overall prediction accuracy. CONCLUSION: Chemotherapy-induced myelosuppression was significantly associated with curative efficacy of 2-cycle chemotherapy in SCLC, which could help predict treatment efficacy and guide chemotherapy dosage.

Plasma levels of urea cycle related amino acids in association with risk of ischemic stroke: Findings from a nested case-control study.

OBJECTIVES: The role of urea cycle related amino acids in the development of ischemic stroke (IS) remains unclear. The study aimed to evaluate the association of these amino acids with IS. MATERIALS AND METHODS: We conducted a case-control study nested within a cohort study in Changshu, Eastern China. A total of 321 cases and 321 controls matched by age and gender were finally included. Plasma levels of ornithine, arginine, spermidine, and proline were measured using ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS). Odds ratios (ORs) and their 95 % confidence intervals (CIs) were calculated by conditional logistic regression analyses. RESULTS: Plasma ornithine was inversely associated with risk of IS [crude OR: 0.62 (95 % CI: 0.40-0.97)]. After adjustment for body mass index, smoking, hypertension, family history of stroke, estimated glomerular filtration rate, and total cholesterol, the corresponding ORs for the highest compared to the lowest quartiles was essentially unchanged [adjusted OR: 0.62 (95 % CI: 0.39-0.99)]. The risk association remained significant after repeating the analyses by excluding the first two years of follow-up. Plasma arginine, spermidine, and proline were not associated with the risk of IS. CONCLUSION: We observed that higher plasma levels of ornithine were associated with a lower risk of incident IS. Our novel findings suggest a protective role of ornithine in the pathogenesis of IS.

Frailty in asthma-COPD overlap: a cross-sectional study of association and risk factors in the NHANES database.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a condition characterised by the simultaneous presence of features of both asthma and COPD. The study aims to investigate the association between ACO and frailty among middle-aged and elderly populations, and identify the risk factors for frailty in individuals with ACO. METHODS: We conducted a cross-sectional study with 34 403 eligible participants (aged ≥40 years) from the National Health and Nutrition Examination Survey 1999-2018 cycles. Participants were stratified into four groups: ACO, asthma, COPD and non-asthma/COPD. Frailty assessment was based on frailty index, generating frail and non-frail group. Univariate and multivariate survey-weighted logistic regression analysis were used to determine the association between ACO and frailty, and to identify the risk factors for frailty in ACO. RESULTS: The frailty prevalence in participants with ACO was 60.2%, significantly higher than that in those with asthma (32.3%) and COPD (40.6%). In the unadjusted model, participants with ACO exhibited six-fold higher odds of frailty (OR 6.30, 95% CI 5.29 to 7.49), which was significantly greater than those with COPD (OR 2.84, 95% CI 2.46 to 3.28) and asthma (OR 1.99, 95% CI 1.80 to 2.18), using the non-asthma/COPD group as a reference. After adjusting for all confounders, participants with ACO had over four times higher odds of frailty (OR 4.48, 95% CI 3.53 to 5.71), still higher than those with asthma and COPD. The findings remained robust in sensitivity and subgroup analyses. Furthermore, hypertension, cancer, cardiovascular disease, chronic kidney disease and cognitive disorders were identified as risk factors for frailty among ACO participants, while higher income and education levels were protective factors. CONCLUSION: Patients (aged ≥40 years) with ACO were at a higher risk of frailty, regardless of age or sex, compared with those with asthma or COPD alone. Greater attention should be paid to patients with ACO, regardless of their age.

Association of weight range with telomere length: A retrospective cohort study.

Objective: Previous research has shown a significant association between weight and telomere length, but did not take into consideration weight range. The study was to investigate the association of weight range with telomere length. Methods: Data of 2918 eligible participants aged 25-84 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 cycle were analyzed. Information about demographic variables, lifestyle factors, anthropometric variables, and medical comorbidities were included. Univariate and multivariate linear regression model with adjustments for potential confounders were employed to determine the association between weight range and telomere length. A non-parametrically restricted cubic spline model was used to illustrate the possible non-linear relationship. Results: In univariate linear regression, BMImax, BMI range, and weight range all revealed significant negative associations with telomere length. However, annual rate of BMI/weight range showed a significant positive associations with telomere length. There was no significant association between telomere length and BMImin. After adjusting for potential confounders, the inverse associations persisted in BMImax (ß=-0.003, P<0.001), BMI range (ß=-0.002, P=0.003), and weight range (ß=-0.001, P=0.001). Furthermore, annual rate of BMI range (ß=-0.026, P=0.009) and weight range (ß=-0.010, P=0.007) presented negative associations with telomere length, after adjusting for covariates in Model 2-4. The association between BMImin (ß =-0.002, P=0.237) and telomere length still could not reach statistical significance in multivariate linear regression model. The results of restricted cubic spline analysis showed that BMImax (P for nonlinear =0.026), BMI range (P for nonlinear =0.022), weight range (P for nonlinear =0.035), annual rate of BMI range (P for nonlinear =0.030), and annual rate of weight range (P for nonlinear =0.027) all had nonlinear inverse associations with telomere length. Conclusions: The study suggests that weight range is inversely associated with telomere length in U.S. adults. Larger weight fluctuation may accelerate telomere shortening and aging.

Age and Genetic Risk Score and Rates of Blood Lipid Changes in China.

Importance: Blood lipids are the primary cause of atherosclerosis. However, little is known about relationships between rates of blood lipid changes and age and genetic risk. Objective: To evaluate associations of blood lipid change rates with age and polygenic risk. Design, Setting, and Participants: This cohort is from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China, which was established from 1998 to 2008. Participants were followed up until 2020 (mean [SD] follow-up, 13.8 [4.3] years) and received 4 repeated lipid measurements. Data analysis was performed from June to August 2022. A total of 47 691 participants with available genotype data were recruited, and 37 317 participants aged 18 years or older were included in the final analysis after excluding participants who were lost to follow-up or with major chronic diseases, and those without blood lipid measurements at baseline and any follow-up survey. Exposures: Age and polygenic risk scores based on 126 lipid-related genetic variants. Main Outcomes and Measures: The estimated annual changes (EAC) of blood lipids in milligrams per deciliter. Results: This study evaluated 37 317 participants (mean [SD] age of 51.37 [10.82] years; 15 664 [41.98%] were male). The associations of EACs of blood lipids with age differed substantially between male and female participants. Male participants experienced declining change as they got older for total cholesterol (EAC, 0.34 [95% CI, 0.14 to 0.54] mg/dL for age <40 years vs 0.01 [95% CI, -0.11 to 0.13] mg/dL for age ≥60 years), triglyceride (EAC, 3.28 [95% CI, 2.50 to 4.07] mg/dL for age <40 years vs -1.70 [95% CI, -2.02 to -1.38] mg/dL for age ≥60 years), and low-density lipoprotein cholesterol (LDL-C) (EAC, 0.15 [95% CI, -0.02 to 0.32] mg/dL for age <40 years vs 0.01 [95% CI, -0.10 to 0.11] mg/dL for age ≥60 years). Female participants had inverse V-shaped associations and the greatest rate of change appeared in the age group of 40 to 49 years (EAC for total cholesterol, 1.33 [95% CI, 1.22 to 1.44] mg/dL; EAC for triglyceride, 2.28 [95% CI, 1.94 to 2.62] mg/dL; and EAC for LDL-C, 0.94 [95% CI, 0.84 to 1.03] mg/dL). Change in levels of blood lipids were also associated with polygenic risk. Participants at low polygenic risk tended to shift toward lower blood lipid levels, with EACs of -0.16 (95% CI, -0.25 to -0.07) mg/dL; -1.58 (95% CI, -1.78 to -1.37) mg/dL; and -0.13 (95% CI, -0.21 to -0.06) mg/dL for total cholesterol, triglyceride, and LDL-C, respectively. Participants with high polygenic risk had the greatest rates of change for total cholesterol, triglyceride, and LDL-C (EAC, 1.12 [95% CI, 1.03 to 1.21] mg/dL; EAC, 3.57 [95% CI, 3.24 to 3.91] mg/dL; and EAC, 0.73 [95% CI, 0.65 to 0.81] mg/dL, respectively). Similar patterns were also observed across sex and age groups. Conclusions and Relevance: In this cohort study, EACs of blood lipids were significantly associated with age and polygenic risk, suggesting that prevention strategies for lipids should focus on individuals with high genetic risk and in the critical age window.

Plasma ß-Alanine is Positively Associated With Risk of Ischemic Stroke: a Nested Case-Control Study.

BACKGROUND: Previous studies suggested that ß-alanine as a neurotransmitter could affect the pathogenesis of ischemic damage. However, the association between circulating ß-alanine and risk of ischemic stroke (IS) has not been evaluated in populations. OBJECTIVES: We aimed to examine the association between ß-alanine and IS risk in a nested case-control study. METHODS: We performed a case-control study nested within a prospective community-based cohort (n = 16457; median follow-up time: 5.3 y), which included 321 incident IS cases and 321 controls matched by age and sex. Β-alanine and other metabolites were measured in plasma after overnight fasting by LC-MS/MS. The association of ß-alanine with risk of IS was evaluated by conditional logistic regression. BMI, current smoking, educational attainment, physical activity, total energy intake, family history of stroke, hypertension, diabetes, hyperlipidemia, and estimated GFR were adjusted in multivariable models. RESULTS: There was a significant Spearman partial correlation between ß-alanine and 4-pyridoxic acid (ρ = 0.239; P < 0.001). Participants with elevated ß-alanine levels were more likely to develop IS with an adjusted OR of 1.26 (95% CI: 1.06-1.51; P = 0.011) (per standard deviation increment). This association remained significant after excluding the first 2 y of follow-up, and after further adjustment for red meat intake, total protein intake, medication use, or vitamin B6 indicators. CONCLUSIONS: Our novel findings revealed that plasma ß-alanine at baseline were positively associated with risk of IS and may function as an early biomarker of IS risk.

Independent and combined effect of income and education attainment on the incidence of stroke events: a large-scale cohort study from rural communities in China.

OBJECTIVES: Few studies have longitudinally evaluated income and education, and their combined effect on incident of stroke in China. METHODS: The present study was based on a cohort with a baseline survey in China. A total of 15,913 participants were finally included. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated to evaluate the association of income, education, and their combination with stroke risk by Cox proportional hazard model. RESULTS: Lower income and less years of education was significantly associated with an increased risk of total stroke [income: adjusted HR: 1.54 (95% CI: 1.22-1.95); education: adjusted HR: 1.59 (95% CI: 1.11-2.28)]. Notably, the highest risk for total stroke was seen among those with lower income and higher education (adjusted HR: 2.46, 95% CI: 1.36-4.47). Sensitivity analysis by excluding the first year of follow-up showed similar findings with the primary analysis. DISCUSSION: Lower income and education attainment were associated with an increased risk of stroke in Chinese countrysides. A joint effect of income and education existed on the risk of developing stroke. Special attention should be paid for rural community residents, especially for people with low income levels.

Associations of adherence to the DASH diet and the Mediterranean diet with chronic obstructive pulmonary disease among US adults.

Background: The Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet are associated with reduced cardiovascular, tumor, and diabetes risk, but the effect on chronic obstructive pulmonary disease (COPD) is uncertain. Objective: To investigate the association of the DASH diet and the Mediterranean diet with the risk of COPD in American adults. Methods: This cross-sectional study included 28,605 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 survey cycle who had complete dietary and other questionnaire data. The scores of healthy eating patterns (the DASH diet and the Mediterranean diet) were derived from a 24-h dietary recall interview [individual food and total nutrient data from NHANES and food pattern equivalents data from the United States Department of Agriculture (USDA)]. The primary outcome was the prevalence of COPD. COPD was defined based on participants self-reported whether or not a doctor or health professional had diagnosed chronic bronchitis or emphysema. Secondary outcomes were lung function and respiratory symptoms. All analyses were adjusted for demographics and standard COPD risk factors (primary tobacco exposure, secondhand smoke exposure, and asthma). Results: This study included 2,488 COPD participants and 25,607 non-COPD participants. We found that a higher DASH diet score was associated with a lower risk of COPD [odds ratio (OR): 0.83; 95% confidence interval (CI): 0.71-0.97; P = 0.021]. This association persisted in several subgroups [men (OR: 0.73; 95% CI: 0.58-0.93; P = 0.010), relatively young (OR: 0.74; 95% CI: 0.55-1.01; P = 0.050), and smoker (OR: 0.82; 95% CI: 0.67-0.99; P = 0.038)]. In contrast, the Mediterranean diet score was not significantly associated with COPD prevalence in this large cross-sectional analysis representative of the US adult population (OR: 1.03; 95% CI: 0.88-1.20; P = 0.697). In addition, we found a correlation between DASH diet adherence and lung function [ß: -0.01; 95% CI: -0.01-0.00; P = 0.003 (FEV1: FVC)] or respiratory symptoms [OR: 0.80; 95% CI: 0.73-0.89; P < 0.001 (dyspnea); OR: 0.80; 95% CI: 0.70-0.91; P = 0.002 (cough); OR: 0.86; 95% CI: 0.74-0.99; P = 0.042 (expectoration)], especially in non-COPD populations. Conclusion: A higher DASH diet score was associated with improved COPD prevalence, lung function and respiratory symptoms. This new finding supports the importance of diet in the pathogenesis of COPD and expands the scope of the association of the DASH diet score with major chronic diseases.

Associations of plasma TMAO and its precursors with stroke risk in the general population: A nested case-control study.

BACKGROUND: Trimethylamine N-oxide (TMAO) is a gut-derived atherogenic metabolite. However, the role of TMAO and its precursors in the development of stroke remains unclear. We aimed to examine the associations between metabolites in TMAO biosynthesis and stroke risk. METHODS: A nested case-control study was performed in a community-based cohort (2013-2018, n = 16,113). We included 412 identified stroke cases and 412 controls matched by age and sex. Plasma carnitine, choline, betaine, trimethyl lysine (TML), and TMAO were measured by ultrahigh performance liquid chromatography-tandem mass spectrometry. Conditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) between these biomarkers and stroke risk. RESULTS: After adjustment for body mass index, smoking, hypertension, educational attainment, and estimated glomerular filtration rate, the corresponding OR for the highest versus lowest quartile was 1.74 (95% CI: 1.16-2.61, P trend = 0.006) for total stroke and 1.81 (95% CI: 1.14-2.86, P trend = 0.020) for ischemic stroke in an essentially linear dose-response fashion. A significant association between TMAO and nonischemic stroke was shown as a J-shape with OR for the highest versus second quartile of 5.75 (95% CI: 1.73-19.1). No meaningful significant risk association was found among plasma carnitine, choline, betaine, and TML with stroke risk. CONCLUSIONS: Increased TMAO was associated with higher stroke risk in the community-based population, whereas the TMAO precursors carnitine, choline, betaine, and TML were not associated. Further studies are warranted to confirm these findings and to further elucidate the role of TMAO in the development of stroke.

A juvenile murine model with chronic lung inflammation induced by repeated intratracheal instillation of lipopolysaccharides: a versatile and replicable model.

Background: Recurrent lower respiratory tract infection or chronic pulmonary infection often occur in children with chronic lung diseases (CLDs). By continuous lung inflammation, recurrent and chronic infection could cause irreversible airway structural and lung function damage, which eventually leads to respiratory failure and death. Methods: In purpose of recapitulating persistent high-intensity lung inflammation caused by recurrent lower respiratory tract infection or chronic infection, we established a juvenile murine model with chronic lung inflammation induced by repeated intratracheal instillations of lipopolysaccharides (LPS) from Pseudomonas aeruginosa once a week for 4 weeks. Four-week-old C57BL/6N mice were divided into 4 groups, including LPS0.5 group (n=15), LPS1.0 group (n=15), Control group (n=15) and Normal group (n=15). Mice in LPS0.5 group and LPS1.0 group were instilled intratracheally with 0.5 mg/kg LPS and 1.0 mg/kg LPS respectively. Mice in control group were instilled intratracheally with LPS-free sterile 0.9% NaCl, whereas normal group received no treatment. The successful chronic lung inflammation murine model was validated via (I) pathological manifestations of chronic inflammatory mononuclear-cell infiltration and lung parenchyma damage; (II) decreased lung function. Results: All mice in LPS1.0 group died before the third instillation. No death after instillation was observed in Control and LPS0.5 group. Histological analysis revealed that in LPS0.5 group, 7 days after the third instillation, most bronchus and parabronchial vessels were wrapped by infiltrating monocytes and lymphocyte and alveolar cavities were compressed, which were not observed in control and normal group. Also, ratio of forced expiratory volume in 0.1 second (FEV0.1) and forced vital capacity (FVC) in LPS0.5 group was significantly lower (P<0.0001) than both control group and normal group, suggesting ventilatory dysfunction developed after repeatedly intratracheal instillation once a week for 4 weeks. Conclusions: Intratracheal instillation of 0.5 mg/kg LPS once a week for 4 weeks can cause chronic lung inflammation in young mice.

Associations of plasma carnitine, lysine, trimethyllysine and glycine with incident ischemic stroke: Findings from a nested case-control study.

BACKGROUND & AIMS: Carnitine biosynthesis has been related to fatty acid oxidation, a process probably exerting neuroprotective effects. However, the role of carnitine biosynthesis in the development of ischemic stroke (IS) remains unclear. We aimed to examine the associations between plasma markers of carnitine biosynthesis and the IS risk. METHODS: We performed a case-control study nested in a community-based cohort (2013-2018, n = 16457). The study included 321 incident cases of IS and 321 controls matched by age and gender. Carnitine, lysine, trimethyllysine (TML), glycine, and their ratios were measured/calculated in the baseline plasma samples using ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS). Conditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS: Plasma carnitine, lysine, TML, and glycine were not significantly associated with the IS risk, although a gradually reduced risk was observed across the increasing tertiles of glycine. Notably, the ratios of glycine/carnitine, glycine/lysine, and glycine/TML were all inversely associated with the IS risk. Compared to the lowest tertiles, the corresponding odds ratios for the highest tertiles were 0.60 (95% CI: 0.40-0.91), 0.63 (95% CI: 0.42-0.94), and 0.63 (95% CI: 0.42-0.95), respectively, after adjustment for body mass index, smoking, hypertension, family history of stroke, estimated glomerular filtration rate and total cholesterol. Repeating the analyses by excluding the first two years of follow-up did not materially alter the risk associations for the ratios of glycine/lysine and glycine/carnitine. CONCLUSIONS: Increased ratios of plasma glycine to carnitine, lysine, and TML were associated with a lower risk of incident IS. Our observational findings suggest that the homeostasis of circulating carnitine, lysine, TML, and glycine may involve in the pathogenesis of IS.

Human Adenovirus Subtype 21a Isolates From Children With Severe Lower Respiratory Illness in China.

Human adenovirus type 21 (HAdV-21) is an important pathogen associated with acute respiratory infection (ARI), but it was rarely reported and characterized so far. In this study, 151 of 1,704 (8.9%) pediatric patients (≤14 years old) hospitalized with ARI in Guangzhou, China in 2019 were positive for HAdV which was the third most frequently detected pathogen. Two HAdV-21-positive patients presented with severe lower respiratory illness and had similar initial symptoms at onset of illness. Then two HAdV-21 strains were isolated and characterized. The two HAdV-21 strains were sequenced and classified as subtype 21a with genomes closely related to strain BB/201903 found in Bengbu, China in March 2019. Phylogenetic analysis for whole genome and major antigen proteins of global HAdV-21 strains showed that HAdV-21 could be classified into two branches, branch 1 including genotype 21p, branch 2 including all other strains dividing into genotype 21a and 21b. There was no significant difference in the plaque size, or the replication curves between the two HAdV-21a strains and the prototype strain HAdV-21p AV-1645. However, there were five highly variable regions (HVR1, HVR3, HVR4, HVR5, and HVR7) in the hexon protein that varied between two branches. Mice immunized with one branch strain showed 2-4-fold lower neutralizing antibody titers against another branch strain. In summary, this study firstly reported two HAdV-21a infections of children in China, characterized two isolates of HAdV-21a associated with severe lower respiratory illness; our results could be important for understanding the HAdV-21 epidemiology and pathogenic, and for developing HAdV-21 vaccine and drug.

Analysis of severe human adenovirus infection outbreak in Guangdong Province, southern China in 2019.

During 2018-2019, a severe human adenovirus (HAdV) infection outbreak occurred in southern China. Here, we screened 18 respiratory pathogens in 1704 children (≤ 14 years old) hospitalized with acute respiratory illness in Guangzhou, China, in 2019. In total, 151 patients had positive HAdV test results; 34.4% (52/151) of them exhibited severe illness. HAdV infection occurred throughout the year, with a peak in summer. The median patient age was 3.0 (interquartile range: 1.1-5.0) years. Patients with severe HAdV infection exhibited increases in 12 clinical indexes (P â€‹≤ â€‹0.019) and decreases in four indexes (P â€‹≤ â€‹0.007), compared with patients exhibiting non-severe infection. No significant differences were found in age or sex distribution according to HAdV infection severity (P â€‹> â€‹0.05); however, the distributions of comorbid disease and HAdV co-infection differed according to HAdV infection severity (P â€‹< â€‹0.05). The main epidemic types were HAdV-3 (47.0%, 71/151) and HAdV-7 (46.4%, 70/151). However, the severe illness rate was significantly higher in patients with HAdV-7 (51.4%) than in patients with HAdV-3 (19.7%) and other types of HAdV (20%) (P â€‹< â€‹0.001). Sequencing analysis of genomes/capsid genes of 13 HAdV-7 isolates revealed high similarity to previous Chinese isolates. A representative HAdV-7 isolate exhibited a similar proliferation curve to the curve described for the epidemic HAdV-3 strain Guangzhou01 (accession no. DQ099432) (P â€‹> â€‹0.05); the HAdV-7 isolate exhibited stronger virulence and infectivity, compared with HAdV-3 (P â€‹< â€‹0.001). Overall, comorbid disease, HAdV co-infection, and high virulence and infectivity of HAdV-7 were critical risk factors for severe HAdV infection; these data can facilitate treatment, control, and prevention of HAdV infection.

Halotherapy relieves chronic obstructive pulmonary disease by alleviating NLRP3 inflammasome-mediated pyroptosis.

Background: Airway remodeling and inflammation are considered the main characteristics of chronic obstructive pulmonary disease (COPD). Cigarette smoke promotes the occurrence of inflammation, oxidative stress, and pyroptosis. Halotherapy has been shown to dilute secretions in the airways and promote drainage, but the mechanism remains unclear. In this study, we evaluated the anti-inflammatory and antioxidant effects of halotherapy in COPD rats and investigated the underlying mechanism. Methods: A COPD rat model was constructed by cigarette smoke and lipopolysaccharide tracheal instillation. A total of 120 male Sprague-Dawley (SD) rats were randomly divided into control, model, halotherapy, terbutaline, halotherapy + terbutaline, and Ac-YVAD-CMK (Caspase-1 inhibitor) groups. After modeling and treatment, the pulmonary function of the rats was measured. Pathological changes in the lungs were measured by hematoxylin-eosin (H&E) staining. Serum interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and nitric oxide (NO) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity in the lungs were determined by biochemical tests. The levels of cluster of differentiation 4 (CD4+) and CD8+ T cells in the blood were determined by flow cytometry. The expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), gasdermin-D (GSDMD), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), Caspase-1, and IL-1ß in lung tissues were detected by immunohistochemistry, Western blotting, or quantitative polymerase chain reaction (qPCR). Results: Halotherapy recovered the clinical symptoms of COPD rats, and reduced lung inflammatory cell infiltration and air wall attenuation. It also relieved oxidative stress in the lung tissue of COPD rats, reduced CD4+ and CD8+ T cell accumulation in lung tissue, and decreased inflammatory factor production in the serum of COPD rats. Furthermore, it inhibited the TLR4/NF-κB/GSDMD and NLRP3/ASC/Caspase-1 signaling pathways. Ac-YVAD-CMK could not completely inhibit the therapeutic effect of halotherapy on COPD rats. Conclusions: Halotherapy improves lung function by inhibiting the NLRP3/ASC/Caspase-1 signaling pathway to reduce inflammation and pyroptosis in COPD rats, and may be a new option for the prevention and treatment of COPD.

Association of total pre-existing comorbidities with stroke risk: a large-scale community-based cohort study from China.

BACKGROUND: Comorbidities, any other coexisting diseases in patients with a particular index disease, are known to increase the mortality of a stroke. However, the association of pre-existing comorbidities with stroke risk has not been fully studied. METHODS: This study included 16,246 adults from a prospective community-based cohort with a baseline survey conducted in 2013 in China. Participants were followed up with hospitalization records and the Cause of Death Registry. The association of eight pre-existing comorbidities (coronary heart disease, hyperlipidemia, hypertension, diabetes, previous stroke, chronic obstructive pulmonary disease, nephropathy, and cancer) with stroke risk was analyzed using the Cox proportional hazard model in 2020. RESULTS: At a median follow-up of 5.5 years, a total of 449 participants (206 men and 243 women) developed a stroke. Four pre-existing comorbidities (hypertension, congenital heart disease, previous stroke, and diabetes) were independently and positively associated with the risk for all types of stroke. The adjusted hazard ratios for participants with only 1 and ≥ 2 pre-existing comorbidities compared with those without pre-existing conditions were 1.96 (95% CI: 1.44, 2.67; P < 0.001) and 2.87 (95% CI; 2.09, 3.94; P < 0.001) for total stroke, respectively. Moreover, male and female participants with a combination of increased age and a higher number of pre-existing comorbidities experienced the greatest risk of stroke. CONCLUSIONS: The number of pre-existing comorbidities was independently associated with an increased risk of stroke. There was a synergic effect between increased age and a higher number of pre-existing comorbidities on stroke occurrence. Our novel findings emphasize the importance and potential application of pre-existing comorbidities as a risk indicator in stroke prevention.

Associations of tea consumption with blood pressure progression and hypertension incidence.

BACKGROUND: Association between tea consumption and incident hypertension remains uncertain. This study conducted to examine the health effects of tea consumption on blood pressure progression and hypertension incidence. METHODS: A population-based cohort of 38,913 Chinese participants without hypertension at baseline were included in the current study. Information on tea consumption was collected through standardized questionnaires. Associations of tea consumption with blood pressure progression and incident hypertension were analyzed using logistic regression models and Cox proportional hazards regression models, respectively. RESULTS: During a median follow-up of 5.9 years, 17,657 individuals had experienced progression to a higher blood pressure stage and 5,935 individuals had developed hypertension. In multivariate analyses, habitual tea drinkers (≥ 3 times/week for at least six months) had a 17% lower risk for blood pressure progression [odds ratio (OR) = 0.83, 95% CI: 0.79-0.88] and a 14% decreased risk for incident hypertension [hazard ratio (HR) = 0.86, 95% CI: 0.80-0.91] compared with non-habitual tea drinkers. Individuals in different baseline blood pressure groups could obtain similar benefit from habitual tea drinking. In terms of tea consumption amount, an inverse, linear dose-response relation between monthly consumption of tea leaves and risk of blood pressure progression was observed, while the risk of incident hypertension did not reduce further after consuming around 100 g of tea leaves per month. CONCLUSIONS: Our study demonstrated that habitual tea consumption could provide preventive effect against blood pressure progression and hypertension incidence.

Association between fasting blood glucose levels and stroke events: a large-scale community-based cohort study from China.

OBJECTIVES: Diabetes mellitus has been associated with stroke. However, the association between fasting blood glucose (FBG) and stroke risk in a general population remains not clear. The purpose of our study was to examine the FBG levels on subsequent stroke risk in a community-based cohort in China. DESIGN: Prospective cohort study, employing Cox proportional hazard model to analyse the association of FBG levels with stroke risk. SETTING: A community-based cohort study included adults participating in a baseline survey conducted in 2013 in Changshu, eastern China. PARTICIPANTS: 16 113 participants were recruited with a multistage sampling method, excluding participants with severe disability, severe cancer, severe psychiatric disturbance or previous stroke before enrolment. PRIMARY OUTCOME MEASURES: Stroke events. RESULTS: During a median follow-up of 5.5 years, 417 incident cases of stroke were identified. The adjusted HR for total and ischaemic stroke for participants in the fourth quartile of FBG compared with the first quartile was 1.44 (95% CI 1.07 to 1.94) and 1.57 (95% CI 1.11 to 2.21), respectively. FBG levels of ≥7.0 mmol/L were associated with an increased risk of stroke based on two clinical classifications (American Diabetes Association: 1.68 (1.24 to 2.27); WHO: 1.62 (1.21, 2.13)). In stratified analyses, risk associations existed in women (HR: 1.92, 95% CI 1.22 to 3.01) and postmenopausal women (HR: 1.68, 95% CI 1.06 to 2.68) for the fourth quartile versus the first. More importantly, the meta-analysis observed a positive association between FBG levels and stroke risk (pooled HR: 1.70, 95% CI 1.27 to 2.29; n=7)). CONCLUSIONS: Higher FBG level was independently associated with an increased risk of stroke in Chinese adults, especially significant in women.