Socioeconomic disparities in the association of age at first live birth with incident stroke among Chinese parous women: A prospective cohort study.

Background: Stroke has become a significant public health issue in China. Although studies have shown that women's age at first live birth (AFLB) might be associated with incident stroke, there is limited evidence on this relationship among Chinese parous women. Likewise, the nature of this association across urban-rural socioeconomic status (SES) has yet to be explored. In this prospective study, we sought to investigate the associations of women's AFLB with the risk of incident stroke and its subtypes (ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage) and to explore the differences of these associations as well as the population-level impacts across SES classes. Methods: We used data on 290 932 Chinese parous women from the China Kadoorie Biobank who were recruited in the baseline survey between 2004 and 2008 and followed up until 2015. We used latent class analysis to identify urban-rural SES classes and Cox proportional hazard regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for AFLB's association with incident stroke. We then calculated population attributable fraction (PAF) to demonstrate the population-level impact of later AFLB on stroke. Results: Around 8.9% of parous women developed stroke after AFLB. Compared with women with AFLB <22 years, those with older AFLB had a higher risk of total stroke, with fully adjusted HRs (95% CI) of 1.71 (95% CI = 1.65-1.77) for 22-24 years and 3.37 (95% CI = 3.24-3.51) for ≥25 years. The associations of AFLB with ischaemic stroke were stronger among rural-low-SES participants. We found the highest PAFs of ischaemic stroke (60.1%; 95% CI = 46.2-70.3) associated with later AFLB for urban-high-SES individuals. Conclusions: Older AFLB was associated with higher risks of incident stroke and its subtypes among Chinese parous women, with stronger associations between AFLB and ischaemic stroke among rural-low-SES participants. Targeted medical advice for pregnant women of different ages could have long-term benefits for stroke prevention.

Paternal and maternal exposures to adverse childhood experiences and spontaneous fetal loss: a nationwide cross-sectional analysis.

BACKGROUND: Adverse childhood experiences (ACEs) might be associated with maternal spontaneous fetal loss, while evidence among Chinese population is limited. This study aims to explore the associations of adverse childhood experiences (ACEs) among women and their spouses with the risk of spontaneous abortion and stillbirth. METHOD: Data were from the China Health and Retirement Longitudinal Study (CHARLS) 2014 survey. ACEs were categorized into intra-familial ACEs and extra-familial ACEs. The associations of maternal and paternal ACEs with women's history of spontaneous abortion and stillbirth were investigated by logistic regression. RESULTS: 7,742 women were included with 9.05% and 2.47% experiencing at least one spontaneous abortion or stillbirth, respectively. Women exposed to 2, 3, and ≥ 4 ACEs were at significantly higher odds of spontaneous abortion, with adjusted odds ratios (ORs) of 1.52 (95% [CI, Confidence Interval] 1.10-2.10), 1.50 (95% CI 1.07-2.09) and 1.68 (95% CI 1.21-2.32), respectively. A significant association between ≥ 4 maternal intra-familial ACEs and stillbirth (OR 2.23, 95% CI 1.12-4.42) was also revealed. Furthermore, paternal exposures to 3 and ≥ 4 overall ACEs were significantly associated with their wives' history of spontaneous abortion, with adjusted ORs of 1.81 (95% CI 1.01-3.26) and 1.83 (95% CI 1.03-3.25), respectively. CONCLUSION: Both maternal and paternal ACEs were associated with spontaneous abortion, and potential mediators might need to be considered to further explore impacts of maternal and paternal ACEs on maternal reproductive health.

Tributyltin-induced oxidative stress causes developmental damage in the cardiovascular system of zebrafish (Danio rerio).

Tributyltin (TBT) can be used as an antifouling agent with anticorrosive, antiseptic and antifungal properties and is widely used in wood preservation and ship painting. However, it has recently been found that TBT can be harmful to aquatic organisms. In this study, to gain insight into the effects of TBT with respect to the development of the cardiovascular system in zebrafish embryos, zebrafish embryos were exposed to different concentrations of TBT solutions (0.2 µg/L, 1 µg/L, and 2 µg/L) at 2 h post-fertilization (hpf) TBT exposure resulted in decreased hatchability and heart rate, deformed features such as pericardial edema, yolk sac edema, and spinal curvature in zebrafish embryos, and impaired heart development. Expression of cardiac development-related genes (vmhc, myh6, nkx2.5, tbx5a, gata4, tbx2b, nppa) is dysregulated. Transgenic zebrafish Tg (fli1: EGFP) were used to explore the effects of TBT exposure on vascular development. It was found that TBT exposure could lead to impaired development of intersegmental vessels (ISVs), common cardinal vein (CCV), subintestinal vessels (SIVs) and cerebrovascular. The expression of vascular endothelial growth factor (VEGF) signaling pathway-related genes (flt1, flt4, kdr, vegfa) was downregulated. Biochemical indices showed that ROS and MDA levels were significantly elevated and that SOD and CAT activities were significantly reduced. The expression of key genes for prostacyclin synthesis (pla2, ptgs2a, ptgs2b, ptgis, ptgs1) is abnormal. Therefore, it is possible that oxidative stress induced by TBT exposure leads to the blockage of arachidonic acid (AA) production in zebrafish embryos, which affects prostacyclin synthesis and consequently the normal development of the heart and blood vessels in zebrafish embryos.

Associations of serum uric acid with hypertension status, stages, phenotypes and progressions among Chinese middle-aged and elderly.

BACKGROUND AND AIMS: No consensus has been reached on the association between serum uric acid (SUA) and hypertension. This study aimed to investigate the associations between SUA and hypertension, including its status, stages, phenotypes and progressions, among middle-aged and older Chinese. METHODS AND RESULTS: Data were obtained from the China Health and Retirement Longitudinal Study 2011-2015. Binary logistic regression was used to evaluate the association between SUA and hypertension status. Multinomial logistic regression was used to explore the associations of SUA with hypertension stages, phenotypes and hypertension status progressions. Models were adjusted for potential confounders and stratified by sex. A total of 7931 individuals aged ≥45 years were included, with 39.16 % of hypertension. Significant associations were found of SUA with stage2 and above hypertension (quartile 4 [Q4] vs quartile 1 [Q1]: odds ratio 1.78, 95 % confidence interval 1.31-2.42, P < 0.001), and systolic diastolic hypertension (SDH) (Q4 vs Q1: 1.53, 1.14-2.06, P = 0.005). In sex stratification, significant associations were found between SUA and stage2 and above hypertension and SDH only for men. Moreover, higher quartiles of baseline SUA showed increased risks of maintained hypertension from 2011 to 2015 (Q3 vs Q1: 1.23, 1.03-1.48, P = 0.024; Q4 vs Q1: 1.73, 1.43-2.10, P < 0.001). CONCLUSION: Higher SUA was associated with hypertension and maintained hypertension among Chinese middle-aged and elderly. Sex-specific associations of SUA with hypertension stages and phenotypes were observed. Regular measurement of SUA in clinical practice may indicate hypertension and its progression, particularly among men.

Meeting the Canadian 24-Hour Movement Guidelines and physical-mental comorbidity among Chinese children and adolescents: Prevalence, associations, and the population impacts.

OBJECTIVES: To examine the association between meeting the Canadian 24-Hour Movement Guidelines and physical-mental comorbidity among children and adolescents in a cross-sectional study. METHODS: A total of 21,061 students aged 11-17 years from Zhejiang Province, China was recruited in the study. We examined the coexistence of five specific physical illnesses - hypertension, high myopia, dental caries, scoliosis, and obesity - with mental illness, specifically depressive symptoms. Generalized linear mixed models were performed to assess the association between overall and specific combinations of movement guidelines and physical-mental comorbidity, presented by odds ratio (OR) and 95% confidence interval (CI). Population attributable fraction (PAF) was calculated to estimate the preventable proportion of comorbid cases via meeting all three movement recommendations. RESULTS: Of the included participants, 19.3% had physical-mental comorbidity. There were 3.8% and 17.0% meeting all three and none of the recommendations, respectively. Meeting at least one recommendation, except for moderate-to-vigorous physical activity recommendation only, was associated with a lower risk of physical-mental comorbidity, with ORs (95% CIs) ranging from 0.72 (0.66-0.79) to 0.40 (0.31-0.51). Meeting more recommendations was associated with decreased comorbid risks, and the association was stronger in 4th-6th graders. The association between specific combinations of recommendations and comorbid risks showed differences by gender and grade. Of the comorbid cases, 42.1% were attributed to not adhering to all three recommendations, and the PAFs varied from 27.4% to 55.7% across different genders and grades. CONCLUSION: Adherence to the 24-h movement guidelines was associated with lower risks of physical-mental comorbidity among children and adolescents.

Lifetime cumulative effect of reproductive factors on ischaemic heart disease in a prospective cohort.

OBJECTIVE: This study aimed to examine the association between lifetime oestrogen exposure and ischaemic heart disease (IHD), based on the hypothesis that higher lifetime oestrogen exposure is linked to lower cardiovascular risk. METHODS: In 2004-2008, lifetime cumulative exposure to reproductive factors was assessed among postmenopausal females from the China Kadoorie Biobank using reproductive lifespan (RLS), endogenous oestrogen exposure (EEE) and total oestrogen exposure (TEE). EEE was calculated by subtracting pregnancy-related and contraceptive use duration from RLS, while TEE by adding up the same components except for lactation. Incident IHD during follow-up (2004-2015) was identified. Stratified Cox proportional hazards models estimated the HRs and 95% CIs of IHD for RLS, EEE and TEE. RESULTS: Among 118 855 postmenopausal females, 13 162 (11.1%) developed IHD during a median follow-up of 8.9 years. The IHD incidence rates were 13.0, 12.1, 12.5, 13.8 per 1000 person-years for RLS Q1-Q4, 15.8, 12.6, 11.3, 12.1 per 1000 person-years for EEE Q1-Q4 and 13.7, 12.3, 12.2, 13.4 per 1000 person-years for TEE Q1-Q4. The highest quartile (Q4) of RLS and TEE were associated with lower risks of IHD (adjusted HR (aHR) 0.95, 95% CI 0.91 to 1.00 and 0.92, 95% CI 0.88 to 0.97, respectively) compared with the lowest quartile (Q1). Longer EEE showed progressively lower risks of incident IHD (aHR 0.93, 95% CI 0.88 to 0.97; 0.88, 95% CI 0.84 to 0.93; 0.87, 95% CI 0.83 to 0.92 for Q2-Q4 vs Q1). CONCLUSIONS: Longer RLS, TEE and EEE were associated with lower risks of IHD among Chinese postmenopausal females.

Combined associations of general obesity and central obesity with hypertension stages and phenotypes among children and adolescents in Zhejiang, China.

General and central obesity are suggested to be associated with elevated blood pressure (BP), whereas few studies have investigated their combined associations with hypertension in children. This study aimed to assess the associations of combinations of general obesity and central obesity with hypertension in Chinese children, including its stages and phenotypes. A total of 5430 children aged 7-17 years in Zhejiang Province were enrolled. General obesity was evaluated by body mass index (BMI), while central obesity was by waist circumference (WC). Then all children were sorted into three mutually exclusive groups: normal weight with or with no central obesity (NW), abnormal weight with no central obesity (AWNCO), and abnormal weight with central obesity (AWCO). Hypertension was defined as either a systolic or diastolic BP ≥ 95th percentile, and further classified into stage 1 hypertension, stage 2 hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic diastolic hypertension (SDH). Logistic regression was used. AWNCO and AWCO were associated with stage 1 hypertension (AWNCO, odds ratio [OR] = 1.94, 95% confidence interval [CI]: 1.59-2.37; AWCO, 2.67, 2.20-3.25), stage 2 hypertension (AWNCO, 2.35, 1.33-4.13; AWCO, 4.53, 2.79-7.37), ISH (AWNCO, 2.50, 1.96-3.18; AWCO, 3.95, 3.15-4.95), and SDH (AWNCO, 2.48, 1.75-3.52; AWCO, 2.78, 1.94-3.99). Children with AWCO were more likely to have stage 1 and stage 2 hypertension, as well as ISH and SDH. The combined measurement of general and central obesity is suggested as an appropriate screening tool for hypertension among children and adolescents.

Associations between adverse childhood experiences and diabetes among middle-aged and older Chinese: a social-ecological perspective.

OBJECTIVES: This study examined the associations between adverse childhood experiences (ACEs) and diabetes within a social-ecological framework, incorporating personal and environmental unfavorable conditions during childhood from family, school, and community contexts. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (2014 life history survey and 2015 survey), including 9,179 participants aged ≥45 years. ACEs were collected through self-report questionnaires, and participants were categorized based on the number of distinct ACEs experienced (0, 1, 2, 3, or ≥4 ACEs). Diabetes was defined by biomarkers, self-reported diagnosis, and treatment status. Logistic regression was conducted to explore the associations between ACEs and diabetes. Subgroup analyses were conducted by gender, age, and obesity status. RESULTS: Compared with participants without ACEs, those exposed to any ACE (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40), 3 ACEs (OR, 1.32; 95% CI, 1.07 to 1.62) and ≥4 ACEs (OR, 1.29; 95% CI, 1.07 to 1.56) had an increased risk of diabetes. For each additional ACE, the risk of diabetes increased by about 5%. Regarding the source of ACEs, those originating from the family (OR, 1.23; 95% CI, 1.08 to 1.41) were associated with diabetes. In terms of specific ACE types, family members with substance abuse (OR, 1.23; 95% CI, 1.01 to 1.52), emotional abuse (OR, 1.28; 95% CI, 1.12 to 1.46), and poor parental relationship (OR, 1.25; 95% CI, 1.09 to 1.43) were associated with diabetes. CONCLUSIONS: ACEs, particularly those originating from the family, were associated with diabetes. Interventions aimed at preventing and mitigating ACEs are essential for the early prevention of diabetes.

Self-rated health, interviewer-rated health, and objective health, their changes and trajectories over time, and the risk of mortality in Chinese adults.

Background: Self-rated health (SRH), interviewer-rated health (IRH), and objective health reflect the overall health status from different aspects. This study aimed to investigate the associations of SRH, IRH, and objective health with mortality among Chinese older adults. Methods: This study used data from the 2008 (baseline), 2011, 2014 and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey. SRH and IRH were evaluated by questionnaire. Objective health was evaluated by the Chinese multimorbidity-weighted index (CMWI), which incorporated 14 diagnosed chronic diseases. SRH, IRH, and CMWI were assessed as: (1) baseline levels; (2) longitudinal changes by subtracting the values obtained in 2008 from the corresponding values in 2014; (3) trajectories by Group-Based Trajectory Modeling, respectively. The Cox proportional hazards model was used to explore the associations of baseline SRH, IRH, and CMWI, their changes, and trajectories with mortality. Results: A total of 13,800 participants were included at baseline (2008). The baseline SRH ([hazard ratio] 0.93, [95% confidence interval] 0.91-0.96), IRH (0.84, 0.81-0.87), and CMWI (0.99, 0.98-1.00) in 2008 were significantly associated with 10-year mortality (2008 to 2018). Among 3,610 participants, the changes of SRH (0.93, 0.87-0.98), IRH (0.77, 0.71-0.83), and CMWI (0.97, 0.95-0.99) from 2008 to 2014 were significantly associated with 4-year mortality (2014-2018). The trajectories were divided into "high SRH/IRH/CMWI" and "low and declining SRH/IRH/CMWI." Compared with "low and declining SRH/IRH/CMWI," "high SRH" (0.58, 0.48-0.70), "high IRH" (0.66, 0.55-0.80), and "high CMWI" (0.74, 0.61-0.89) from 2008 to 2014 were significantly associated with 4-year mortality (2014-2018). Conclusion: Baseline SRH, IRH, and CMWI, their changes and trajectories are all associated with mortality in Chinese older adults. It is possibly necessary to promote the use of cost-effective indicators in primary medical institutions to improve the health management of the older adults.

Spousal concordance in adverse childhood experiences and the association with depressive symptoms in middle-aged and older adults: findings across China, the US, and Europe.

Background: Adverse childhood experiences (ACEs) are associated with higher depressive risks in adulthood. Whether respondents' ACEs are associated with their own depressive symptoms in adulthood and whether this association extends to their spouses' depressive symptoms remain unexplored. Methods: Data were from China Health and Retirement Longitudinal Study (CHARLS), the Health and Retirement Study (HRS), and the Survey of Health, Ageing and Retirement in Europe (SHARE). ACEs were categorized into overall, intra-familial, and extra-familial ACEs. Correlations of couples' ACEs were calculated using Cramer's V and partial Spearman's correlation. Associations of respondents' ACEs with spousal depressive symptoms were assessed using logistic regression, and mediation analyses were conducted to explore the mediating role of respondents' depressive symptoms. Results: Significant associations between husbands' ACEs and wives' depressive symptoms, with odds ratios (ORs) and 95% confidence intervals (CIs) of 2.09 (1.36-3.22) for 4 or more ACEs in CHARLS, and 1.25 (1.06-1.48) and 1.38 (1.06-1.79) for 2 or more ACEs in HRS and SHARE. However, wives' ACEs were associated with husbands' depressive symptoms only in CHARLS and SHARE. Findings in intra-familial and extra-familial ACEs were consistent with our main results. Additionally, respondents' depressive symptoms mediated more than 20% of the effect of respondents' ACEs on spousal depressive symptoms. Conclusion: We found that ACEs were significantly correlated between couples. Respondents' ACEs were associated with spousal depressive symptoms, with respondents' depressive symptoms mediating the association. The bidirectional implications of ACEs on depressive symptoms should be considered within household and effective interventions are warranted.

Association between glycolipids and risk of obstructive sleep apnea: A population-based study.

Background: This study aimed to investigate the associations between multiple glycolipid biomarkers and the risk of obstructive sleep apnea (OSA). Methods: Participants (10,286) aged from 35 to 74 years old were included in this cross-sectional study from the baseline survey of the Guangzhou Heart Study. OSA was ascertained using both Berlin Questionnaire and STOP-BANG Questionnaire. Fasting blood samples were collected from each participant; fasting blood glucose (FBG) and serum concentrations of high-density lipoprotein cholesterol (HDL-CH), low-density lipoprotein cholesterol (LDL-CH), total cholesterol (TC), and triglyceride (TG) were determined. Odds ratio (OR) with 95% confidence interval (CI) was calculated using the multivariate logistic regression model after adjustment for covariates. Results: Of the participants included, 15.56% were categorized into the pre-OSA group, and 8.22% into the OSA group. When comparing the highest with the lowest quartiles, HDL-HC was associated with a 22% (OR: 0.78, 95% CI: 0.65-0.94) and 41% (OR: 0.59, 95% CI: 0.45-0.78) reduced risk of pre-OSA and OSA, triglyceride was associated with a 32% (OR 1.32, 95% CI 1.08-1.60) and a 56% (OR 1.56, 95% CI 1.18-2.07) increased risk of pre-OSA and OSA, and FBG was associated with a 1.37-fold (95% CI 1.13-1.67) risk of pre-OSA and 1.38-fold (95% CI 1.03-1.85) risk of OSA. A significant exposure-response trend was observed for HDL-HC, TG, and FBG with both OSA and Pre-OSA (all p < 0.05). No significant association of LDL-CH and TC with the risk of both pre-OSA and OSA was observed. Conclusion: The findings suggest that serum HDL-CH was inversely associated with OSA risk, while elevated serum TG and FBG could increase the risk of OSA. Healthy glycolipid metabolism warrants more attention in the field of OSA prevention.

The associations of obesity phenotypes with the risk of hypertension and its transitions among middle-aged and older Chinese adults.

OBJECTIVES: This study aimed to investigate the associations of obesity phenotypes with hypertension stages, phenotypes, and transitions among middle-aged and older Chinese. METHODS: Using the 2011-2015 waves of the China Health and Retirement Longitudinal Study, we conducted a cross-sectional analysis included 9,015 subjects and a longitudinal analysis included 4,961 subjects, with 4,872 having full data on the hypertension stage and 4,784 having full data on the hypertension phenotype. Based on body mass index and waist circumstance, subjects were categorized into 4 mutually exclusive obesity phenotypes: normal weight with no central obesity (NWNCO), abnormal weight with no central obesity (AWNCO), normal weight with central obesity (NWCO), and abnormal weight with central obesity (AWCO). Hypertension stages were classified into normotension, pre-hypertension, stage 1 hypertension, and stage 2 hypertension. Hypertension phenotypes were categorized as normotension, pre-hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). The association between obesity phenotypes and hypertension was estimated by logistic regression. A comparison between different sexes was conducted by testing the interaction effect of sex. RESULTS: NWCO was associated with normal→stage 2 (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.11 to 3.42), maintained stage 1 (OR, 1.62; 95% CI, 1.14 to 2.29), and normal→ISH (OR, 1.39; 95% CI, 1.05 to 1.85). AWCO was associated with normal→stage 1 (OR, 1.75; 95% CI, 1.40 to 2.19), maintained stage 1 (OR, 2.77; 95% CI, 2.06 to 3.72), maintained stage 2 (OR, 2.80; 95% CI, 1.50 to 5.25), normal→ISH (OR, 1.56; 95% CI, 1.20 to 2.02), and normal→SDH (OR, 2.54; 95% CI, 1.72 to 3.75). An interaction effect of sex existed in the association between obesity phenotypes and hypertension stages. CONCLUSIONS: This study highlights the importance of various obesity phenotypes and sex differences in hypertension progression. Tailored interventions for different obesity phenotypes may be warranted in hypertension management, taking into account sex-specific differences to improve outcomes.

Associations of the Triglyceride and Glucose Index With Hypertension Stages, Phenotypes, and Their Progressions Among Middle-Aged and Older Chinese.

Objectives: To assess the associations of the triglyceride and glucose (TyG) index with hypertension stages, phenotypes, and their progressions. Methods: The data originated from the China Health and Retirement Longitudinal Study. Multinomial logistic regression investigated the associations of the TyG index with hypertension stages (stage 1, stage 2), phenotypes (isolated systolic hypertension [ISH], isolated diastolic hypertension [IDH], systolic diastolic hypertension [SDH]), their progressions. Results: Compared with the lowest quartile of TyG index, the highest quartile was associated with increased risks of stage 1 hypertension (OR 1.71, 95% CI 1.38-2.13), stage 2 (1.74, 1.27-2.38), ISH (1.66, 1.31-2.11), IDH (2.52, 1.26-5.05), and SDH (1.65, 1.23-2.23). Similar results were found when TyG index was a continuous variable. From 2011 to 2015, a higher baseline TyG index was associated with normotension to stage 1 (per-unit: 1.39, 1.16-1.65), normotension to ISH (per-unit: 1.28, 1.04-1.56), and normotension to IDH (per-unit: 1.94, 1.27-2.97). Conclusion: The TyG index was associated with different hypertension stages, phenotypes, their progressions, and could be served as a surrogate indicator for early hypertension management.

Aptamer-Based Targeted Delivery of Functional Nucleic Acids.

Functional nucleic acid (NA)-based drugs have a broad range of applications since they allow the alteration and control of gene/protein expression patterns in cells. In principle, functional NAs need to be transported precisely and efficiently to target cells to guarantee both functionality and safety. Owing to their negative charges, it is difficult for natural NAs to cross the cell membrane composed of lipid bilayer and enter targeted cells. Worse still, the delivery of undirected functional NAs to nontargeted healthy cells and/or tissues would induce unpredictable adverse effects. Therefore, the precisely targeted delivery of functional NAs to specific cells/organs, particularly in extrahepatic sites, is required. Since aptamers can bind to various proteins on the cell surface with high specificity and selectivity, they can serve as the molecular recognition units to accurately bind target cells and subsequently enable the efficient delivery of cargo. In this perspective, we summarize the original, proof-of-concept aptamer-based strategies for the targeted delivery of functional NAs. A few specific examples are then discussed, followed by our perspectives on some of the challenges and opportunities that lie ahead.

Effect of physical activity on the risk of frailty: A systematic review and meta-analysis.

OBJECTIVE: The relationship between physical activity (PA) and the risk of frailty has not reached a conclusive result. This systematic review with meta-analysis aimed to evaluate the effect of PA on the onset of frailty in the community-dwelling middle and older age adults by pooling data from cohort studies. METHODS: A systematic literature search was performed via PubMed, Embase, and Web of Science up to June 01, 2021. Pooled adjusted effect estimates (ES) with 95% confidence interval (CI) were calculated by using the random-effect model and by comparing the highest with lowest levels of PA. Heterogeneity was tested using the I2 statistic and Q-test. The quality of evidence was evaluated by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: A total of ten cohort studies with 14 records were selected, and the GRADE approach classified the quality of evidence as low. In comparison with the lowest level of PA, the highest level of PA was associated with 41% decreased odds of frailty (ES: 0.59, 95% CI: 0.51-0.67; I2 = 70.0%, P-heterogeneity < 0.001) after pooling results from included studies. In stratified analysis by frailty assessment approach, the highest level of PA was significantly associated with 37% (ES 0.63, 95% CI: 0.52-0.77, 49% (ES: 0.51, 95% CI: 0.41-0.63), and 30% (ES: 0.70, 95% CI: 0.65-0.75) reduced odds of frailty when pooling studies using criteria of physical frailty, multidimensional model, and accumulation of disability, respectively. Stratified analyses further by PA indicators and PA assessment tools yielded similar protective effects in any subgroups. CONCLUSIONS: This study with moderate-certainty evidence shows that a higher level of PA was associated with lower odds of frailty, and the benefits of PA for frailty prevention were independent of frailty assessment tools, PA indicators, and PA assessment methods. Findings from this study may help implement active exercise strategies to prevent frailty.

Adverse childhood experiences and risk of diabetes: A systematic review and meta-analysis.

Background: The association between adverse childhood experiences (ACEs) and diabetes is unclear. This systematic review and meta-analysis aims to quantify the association between the number and types of ACEs and diabetes during adulthood based on available observational studies. Methods: A comprehensive literature search of studies exploring the association between ACEs and diabetes was conducted in PubMed, Medline, and Embase databases until 15 April 2022. A random-effects model was used to pool odds ratios (ORs) and 95% confidence intervals (CIs) for the number and types of ACEs with diabetes. Regarding the association between the number of ACEs and diabetes, we used funnel plots to examine publication bias, subgroup analysis to explore sources of heterogeneity, and sensitivity analysis to explore the robustness of the pooled results. Results: A total of 49 studies were included. Individuals with higher continuous ACEs (per each additional ACE: OR = 1.06, 95% CI = 1.02-1.10), any ACE (OR = 1.22, 95% CI = 1.16-1.28), or ≥4 ACEs (OR = 1.44, 95% CI = 1.27-1.63) were at an increased risk of diabetes in adulthood when compared with individuals without ACEs. Across specific ACE types, childhood economic adversity (OR = 1.11, 95% CI = 1.04-1.19), physical abuse (OR = 1.14, 95% CI = 1.07-1.21), sexual abuse (OR = 1.25, 95% CI = 1.12-1.39), verbal abuse (OR = 1.11, 95% CI = 1.03-1.20), and incarceration (OR = 1.22, 95% CI = 1.03-1.45) were associated with diabetes. However, neglect, emotional abuse, domestic violence, parental divorce or separation, parental death, and living with a family member with substance abuse or mental disorders were not significantly associated with diabetes. Conclusions: Individuals with ACEs may have a cumulative risk for diabetes in adulthood. It is critical to prevent ACEs and build resilience in individuals affected by ACEs.

Status and transition of normal-weight central obesity and the risk of cardiovascular diseases: A population-based cohort study in China.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) has become a growing public health concern. Normal weight central obesity (NWCO) has emerged as a potential risk factor for cardiometabolic dysregulation. To date, the association between NWCO and new-onset CVDs remains unclear. We aimed to evaluate the associations of NWCO and its longitudinal transitions with cardiovascular risks in middle-aged and older Chinese. METHODS AND RESULTS: Data were from the China Health and Retirement Longitudinal Study 2011-2018. NWCO was defined as the combination of a body mass index (BMI) of <24.0 kg/m2 and a waist circumference (WC) of >85 cm in males or >80 cm in females. CVDs included heart diseases and stroke. Cause-specific hazard models and subdistribution hazard models with all-cause death as the competing event were applied. In 2011, 9856 participants without prior CVDs were included, of whom 1814 developed CVDs during a 7-year follow-up. Compared to normal weight and non-central obesity (NWNCO), NWCO was significantly associated with new-onset CVDs, with cause-specific hazard ratios (cHRs) and 95% confidence intervals (CIs) of 1.21 (1.04-1.41) for heart diseases and 1.40 (1.11-1.76) for stroke. From 2011 to 2013, 571 NWNCO participants developed NWCO who subsequently demonstrated a 45% higher risk of CVDs than those with maintained NWNCO. CONCLUSION: NWCO and transition from NWNCO to NWCO are associated with higher risks of CVDs. Identification and prevention of NWCO may be useful in the management of CVDs.

Risk of functional disability associated with solid fuel use and population impact of reducing indoor air pollution in China: A national cohort study.

Background: In China, numerous people still rely on solid fuel for household use. To date, the association between household solid fuel use and functional disability, and what benefit reducing household solid fuel usage could bring at the population level to China remain unclear. Method: Data were from the China Health and Retirement Longitudinal Study. Household fuel was classified as clean or solid for cooking or heating. Functional disability was defined as difficulties in any item of activities of daily living (ADL) or instrumental activities of daily living (IADL). The associations of household fuel use in 2011 and its transitions between 2011 and 2013 with subsequent ADL or IADL disability were assessed with Cox proportional-hazards models. The number of events prevented in a population (NEPP) was generated to estimate how many functionally disabled patients could be prevented by reducing solid fuel usage. Results: A total of 6,216 and 9,716 participants without prior ADL or IADL disability in 2011 were included. Solid (vs. clean) fuel users were more likely to develop ADL and IADL disability, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.37 (1.28~1.45) and 1.38 (1.31~1.46) for using both solid cooking and heating fuel. Furthermore, participants that switched heating fuel from solid to clean (vs. keep solid) were about 20% less likely to develop functional disability. Cooking fuel use switching from solid to clean (vs. keep solid) was also negatively associated with IADL disability (HR = 0.84, 95% CI 0.74~0.96). Over the next 7 years, raising clean fuel usage to 80% could prevent about 4.9 million ADL disability and 2.6 million IADL disability among Chinese aged 45 and older. Conclusion: Household solid fuel use was a risk factor for functional disability. Reducing solid fuel usage could help reduce the burden of functional disability in the current aging society of China.

Photothermolysis Mediated by Gold Nanorods Conjugated with Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody Induces Apoptosis via the Mitochondrial Apoptosis Pathway in Laryngeal Squamous Cell Cancer.

Gold nanorods (AuNRs) have unique optical properties and biological affinity and can be used to treat tumors when conjugated with other protein molecules. Our previous studies have shown that EGFR monoclonal antibody (EGFRmAb)-modified AuNRs exert strong antitumor activity in vitro by inducing apoptosis. In this study, we tested the effects of EGFRmAb-modified AuNRs on laryngeal squamous cell cancer (LSCC) in vitro and in vivo. The in vitro results showed that EGFRmAb-modified AuNRs inhibited NP-69, BEAS-2B and Hep-2 cell growth and induced mitochondria-dependent apoptosis. The mitochondrial membrane potential was reduced, leading to the release of cytochrome C (Cyt C) and consequent activation of the intrinsic mitochondrial apoptosis pathway. Moreover, we observed that the occurrence of mitochondrial apoptosis is related to the destruction of the lysosome-mitochondria axis. To verify the effects in vivo, we also established a laryngeal tumor model in nude mice by subcutaneous transplantation. In model mice treated with EGFRmAb-modified AuNRs and irradiated with an NIR laser, tumor cell apoptosis and tumor growth were inhibited. These results suggest that EGFRmAb-modified AuNRs induced apoptosis through the intrinsic mitochondrial apoptotic pathway and are a potential candidate for cancer therapy.

Associations between Adverse Childhood Experiences and Obesity in a Developing Country: A Cross-Sectional Study among Middle-Aged and Older Chinese Adults.

BACKGROUND: The association between adverse childhood experiences (ACEs) and obesity in developing countries has been underexplored and inconsistent. METHODS: This cross-sectional study used data of 10,054 adults aged ≥ 45 years from the China Health and Retirement Longitudinal Study. Information on 12 ACE indicators was collected via questionnaires. General obesity was defined as a body mass index (BMI) of ≥28 kg/m². Central obesity was defined as a waist circumference of ≥90 cm for males and ≥85 cm for females. Logistic and linear regression analyses were conducted to evaluate the association of ACEs with general obesity, central obesity, BMI, and waist circumference where appropriate. RESULTS: Compared to the non-exposed group, the experience of ≥3 ACEs was significantly associated with decreased risks of general obesity (OR = 0.83, 95% CI: 0.69, 0.999), central obesity (OR = 0.88, 95% 0.77, 0.997), and smaller BMI (ß = -0.27, 95% CI: -0.50, -0.04) and waist circumference (ß = -0.89, 95% CI: -1.52, -0.26). Compared to the high socioeconomic status (SES) group, such associations were more evident in those with a low SES, except for central obesity. CONCLUSION: ACEs were shown to be inversely associated with later-life obesity in China, especially in socioeconomically disadvantaged populations. The context-specific impacts reflect divergent roles of socioeconomic position in the obesity epidemic between developed and developing countries. Further investigations are needed to confirm whether physical activity could shift the direction of this association.