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BACKGROUND: To examine the associations of physical activity (PA) and sedentary behavior (SB) with longevity and age acceleration (AA) using observational and Mendelian randomization (MR) studies, and quantify the mediating effects of lipids. METHODS: In Guangzhou Biobank Cohort Study (GBCS), PA and SB were assessed by the Chinese Version of the International Physical Activity Questionnaire. Longevity was defined as participants whose age at follow-up or at death was at or above the 90th age percentile. AA was defined as the residual resulting from a linear model that regressed phenotypic age against chronological age. Linear regression and Poisson regression with robust error variance were used to assess the associations of total and specific PA in different intensities, and SB with AA and longevity, yielding ßs or relative risks (RRs) and 95% confidence intervals (CIs). Two-sample MR was conducted to examine the causal effects. Mediation analysis was used to assess the mediating effects of lipids. RESULTS: Of 20,924 participants aged 50 + years in GBCS, during an average follow-up of 15.0 years, compared with low PA, moderate and high PA were associated with higher likelihood of longevity (RR (95% CI): 1.56 (1.16, 2.11), 1.66 (1.24, 2.21), respectively), and also cross-sectionally associated with lower AA (ß (95% CI): -1.43 (-2.41, -0.45), -2.09 (-3.06, -1.11) years, respectively). Higher levels of moderate PA (MPA) were associated with higher likelihood of longevity and lower AA, whereas vigorous PA (VPA) showed opposite effects. The association of PA with longevity observed in GBCS was mediated by low-density lipoprotein cholesterol (LDL-C) by 8.23% (95% CI: 3.58-39.61%), while the association with AA was mediated through LDL-C, triglycerides and total cholesterol by 5.13% (3.94-7.30%), 7.81% (5.98-11.17%), and 3.37% (2.59-4.80%), respectively. Additionally, in two-sample MR, SB was positively associated with AA (ß (95% CI): 1.02 (0.67, 1.36) years). CONCLUSIONS: PA showed protective effects on longevity and AA, with the effects being partly mediated through lipids. Conversely, SB had a detrimental impact on AA. MPA was associated with higher likelihood of longevity and reduced AA, whereas VPA showed adverse effects. Our findings reinforce the recommendation of "sit less and move more" to promote healthy longevity, and highlight the potential risks associated with VPA in the elderly.

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Tea consumption is avoided by some due to concerns about its potential to cause anemia. To clarify this impact, we assessed the association between tea intake and anemia in a Chinese prospective cohort study and by Mendelian randomization (MR). We analyzed associations of tea intake with anemia using data from the baseline (N = 30 085) and three subsequent follow-ups (the first: N = 17 898; the second: N = 10 435; the third: N = 5311) in the Guangzhou Biobank Cohort Study (GBCS). We also assessed the causal effect of tea intake on anemia, hemoglobin (Hgb) and hematocrit (Hct) using two-sample MR with summary statistics from relevant genome-wide association studies and the UK Biobank (N = 447 485). At the baseline, compared with never-drinkers, regular tea drinkers had higher levels of Hgb and Hct and a lower risk of anemia after adjustment for confounders (all P < 0.05; all P for trend ≤0.006). Prospectively, compared with never-drinkers, regular tea drinkers had higher Hgb (g L-1) (ß = 0.69; 95% CI, 0.28 to 1.10; P for trend <0.001) and Hct (%) (ß = 0.30; 95% CI, 0.19 to 0.41; P for trend <0.001), but no significant difference in anemia risk (OR = 0.91; 95% CI, 0.82 to 1.02; P for trend = 0.071). MR analyses showed no association between tea intake and anemia, Hgb and Hct. Through triangulation of evidence using a Chinese cohort and genetics, tea consumption appears unlikely to impact anemia risk.

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BACKGROUND: Whether material deprivation-related childhood socio-economic disadvantages (CSD) and care-related adverse childhood experiences (ACE) have different impacts on depressive symptoms in middle-aged and older people is unclear. METHODS: In the Guangzhou Biobank Cohort Study, CSD and ACE were assessed by 7 and 5 culturally sensitive questions, respectively, on 8,716 participants aged 50+. Depressive symptoms were measured by 15-item Geriatric Depression Scale (GDS). Multivariable linear regression, stratification analyses, and mediation analyses were done. RESULTS: Higher CSD and ACE scores were associated with higher GDS score in dose-response manner (P for trend <0.001). Participants with one point increment in CSD and ACE had higher GDS score by 0.11 (95% confidence interval [CI], 0.09-0.14) and 0.41 (95% CI, 0.35-0.47), respectively. The association of CSD with GDS score was significant in women only (P for sex interaction <0.001; women: ß (95% CI)=0.14 (0.11-0.17), men: 0.04 (-0.01 to 0.08)). The association between ACE and GDS score was stronger in participants with high social deprivation index (SDI) (P for interaction = 0.01; low SDI: ß (95% CI)=0.36 (0.29-0.43), high SDI: 0.64 (0.48-0.80)). The proportion of association of CSD and ACE scores with GDS score mediated via education was 20.11% and 2.28%. CONCLUSIONS: CSD and ACE were associated with late-life depressive symptoms with dose-response patterns, especially in women and those with low adulthood socio-economic status. Education was a major mediator for CSD but not ACE. Eliminating ACE should be a top priority.

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The advancement of intelligent road systems in developing countries poses unique challenges in identifying risk factors and implementing safety strategies. The variability of factors affecting crash injury severity leads to different risks across levels of roadway smartness, especially in hazardous terrains, complicating the adaptation of smart technologies. Therefore, this study investigates the temporal instability of factors affecting injury severities in crashes across various terrains, with a focus on the evolution of road smartness. Crash data from selected complex terrain regions in Shaanxi Province during smart road adaptation were used, and categorized into periods before, during, and after smart road implementations. A series of mixed logit models were employed to account for unobserved heterogeneity in mean and variance, and likelihood ratio tests were conducted to assess the spatio-temporal instability of model parameters across different topographic settings and smart processes. Moreover, a comparison between partially constrained and unconstrained temporal modeling approaches was made. The findings reveal significant differences in injury severity determinants across terrain conditions as roadway intelligence progressed. On the other hand, certain factors like pavement damage, truck and pedestrian involvement were identified that had relatively stable effects on crash injury severities. Out-of-sample predictions further emphasize the need for modeling across terrain and roadway development stages. These insights are crucial for developing tailored safety measures for smart road retrofitting in different terrain conditions, thereby supporting the transition towards smarter road systems in developing regions.

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This work presents two Wilkinson power dividers (WPDs) using multi-layer pseudo coplanar waveguide (PCPW) structures. The PCPW-based WPDs were designed, implemented, and verified in a standard 180 nm CMOS process. The proposed PCPW features high slow-wave and low-loss performances compared to other common transmission lines. The two WPDs are based on the same PCPW structure parameters in terms of line width, spacing, and used metal layers. One WPD was realized in a straight PCPW-based layout, and the other WPD was realized in a meandered PCPW-based layout. Both the two WPDs worked up to V-band frequencies, as expected, which also demonstrates that the PCPW guiding structure is less susceptible to the effects of meanderings on the propagation constant and characteristic impedance. The meandered design shows that the measured insertion losses were about 5.1 dB, and its return losses were better than 17.5 dB at 60 GHz. In addition, its isolation, amplitude imbalance, and phase imbalance were 18.5 dB, 0.03 dB, and 0.4°, respectively. The core area was merely 0.2 mm × 0.23 mm, or 1.8 × 10-3λo2.

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Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a new gene implicated in PD and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD and parkinsonism to perinatal lethality with neurological manifestations across 15 unrelated pedigrees with 22 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants impair mitochondrial membrane potential, dynamics and mitophagy in patient-derived fibroblasts. Additionally, we develop models of psmf1 knockdown Drosophila and Psmf1 conditional knockout mouse exhibiting age-dependent motor impairment, with diffuse gliosis in mice. These findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor.

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Background: Poor oral hygiene is associated with overall wellness, but evidence regarding associations of oral health with all-cause mortality remain inconclusive. We aimed to examine the associations of oral health with all-cause and cause-specific mortality in middle-aged and older Chinese adults. Methods: 28 006 participants were recruited from 2003-2008 and followed up until 2021. Oral health was assessed by face-to-face interview and causes of death was identified via record linkage. Cox regression yielded hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment of multiple potential confounders. Results: During an average of 14.3 years of follow-up, we found that a lower frequency of toothbrushing was associated with higher risks of all-cause mortality with a dose-response pattern (P for trend <0.001). Specially, the adjusted HR (95% CI) (vs. ≥ twice/d) was 1.16 (1.10, 1.22) (P < 0.001) for brushing once/d and 1.27 (1.00, 1.61) (P = 0.048) for < once/d. Similar associations were also found for cardiovascular disease (CVD), stroke, and respiratory disease mortality, but not for ischemic heart disease (IHD) and cancer mortality. A greater number of missing teeth was also associated with higher risks of all-cause, CVD, stroke, and respiratory disease mortality with a dose-response pattern (all P for trend <0.05). The association of missing teeth with all-cause mortality was stronger in lower-educated participants. Conclusions: Both less frequent toothbrushing and a greater number of missing teeth were associated with higher risks of all-cause, CVD, stroke, and respiratory disease mortality, showing dose-response patterns, but not with IHD and cancer mortality. Moreover, the dose-response association of missing teeth with all-cause mortality was stronger in lower-educated participants.

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Background: Pharmaceutical management is a new frontier subject between pharmacy, law and management, and related research involves the whole process of drug development, production, circulation and use. With the development of medical systems and the diversification of patients' drug needs, research in the field of pharmaceutical management is becoming increasingly abundant. To clarify the development status of this field, this study conducted a bibliometric analysis of relevant literature in the field based on the knowledge graph method for the first time and explored the evolutionary trends of research hotspots and frontiers. Methods: Literature was obtained from the Web of Science Core Collection database. CiteSpace 6.2.R4 (Advanced), VOSViewer, Scimago Graphica, Pajek and the R programming language were used to visualize the data. Results: A total of 12,771 publications were included in the study. The publications in the field of pharmaceutical management show an overall increasing trend. In terms of discipline evolution, early research topics tended to involve the positioning of pharmacists and pharmaceutical care and the establishment of a management system. From 2000 to 2005, this period tended to focus on clinical pharmacy and institutional norms. With the development of globalization and the market economy, research from 2005 to 2010 began to trend to the fields of drug markets and economics. From 2010 to 2015, research was gradually integrated into health systems and medical services. With the development of information technology, after 2015, research in the field of pharmaceutical management also began to develop in the direction of digitalization and intelligence. In light of the global pandemic of COVID-19, research topics such as drug supply management, pharmaceutical care and telemedicine services under major public health events have shown increased interest since 2020. Conclusion: Based on the knowledge mapping approach, this study provides a knowledge landscape in the field of pharmaceutical management research. The results showed that the reform of pharmacy education, the challenge of drug management under the COVID-19 pandemic, digital transformation and the rise of telemedicine services were the hot topics in this field. In addition, the research frontier also shows the broad prospects of the integration of information technology and pharmaceutical management, the practical value of precision pharmaceutical services, the urgent need of global drug governance, and the ethical and legal issues involved in the application of artificial intelligence technology in drug design, which points out the direction for the future development of pharmaceutical practice.

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Lung cancer is the most common malignant tumor and the second most common malignant tumor in terms of mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, the first-line standard treatment for advanced NSCLC is immunotherapy and targeted therapy. Although these treatments prolong the survival of patients, acquired drug resistance is still inevitable. Antibody-drug conjugates (ADCs) are a new type of anti-tumor drug made by coupling cytotoxic payloads to specific monoclonal antibodies via linkers. Compared with chemotherapy drugs, ADCs have the advantages of accurate recognition, local release, and high patient tolerance. In recent years, they have shown good clinical benefits in the treatment of NSCLC. This article provides an overview of the mechanism of action of ADCs, clinical studies progress in advanced NSCLC, and existing problems and challenges.
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Objective: To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons (PAHs) during critical brain development and explore their potential link with the intestinal microbiota. Methods: Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs (OH-PAHs) in 36-month-old children. Subsequently, 37 children were categorized into low- and high-exposure groups based on the sum of the ten OH-PAHs. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples. Furthermore, fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results: The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group (variable importance for projection > 1, P < 0.05). Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene, fluorine, and phenanthrene ( r = 0.336-0.531). The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states, including amino acid, lipid, and nucleotide metabolism. Additionally, these distinct metabolites were significantly associated with specific intestinal flora abundances ( r = 0.34-0.55), which were mainly involved in neurodevelopment. Conclusion: Higher PAH exposure in young children affected metabolic homeostasis, particularly that of certain gut microbiota-derived metabolites. Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

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BACKGROUND: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample. METHODS: We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin. RESULTS: In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers. CONCLUSIONS: Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.

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This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.

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INTRODUCTION: A standardized measure for inflammaging is lacking. We introduced the inflammatory age (iAge) as a quantification method and explored its associations with age-related traits and diseases in an older Chinese cohort. METHODS: Inflammatory markers including white blood cell count (WBC), neutrophils, lymphocytes, monocytes, C-reactive protein, platelets and albumin were measured. Quantitative real-time polymerase chain reaction was used to measure telomere length. Traditional multivariable linear, partial least squares, and logistic regression were used. RESULTS: iAge was constructed based on WBC, neutrophils, monocytes and albumin, which were associated with telomere length independently. A higher iAge indicated a heavier aging-related inflammation burden. Per 1-year increase in iAge was associated with higher body mass index (ß 0.86 (95 % CI 0.67, 1.05) kg/m2), waist circumference (ß 2.37 (95 % CI 1.85, 2.90) cm), glycosylated hemoglobin A1c (ß 0.06 (95 % CI 0.02, 0.10) %), systolic blood pressure (ß 1.06 (95 % CI 0.10, 2.03) mmHg), triglycerides (ß 0.05 (95 % CI 0.01, 0.08) mmol/L), 10-year cardiovascular diseases risk (ß 0.05 (95 % CI 0.02, 0.08) %), diabetes (OR 1.22 (95 % CI 1.02, 1.46)), hypertension (OR 1.21 (95 % CI 1.04, 1.42)) and metabolic syndrome risks (OR 1.25 (95 % CI 1.04, 1.51)), and lower fasting plasma glucose (ß -0.016 (95 % CI -0.024, -0.007) mmol/L), total cholesterol (ß -0.06 (95 % CI -0.12, -0.01) mmol/L) and high-density lipoprotein cholesterol (ß -0.05 (95 % CI -0.07, -0.03) mmol/L). CONCLUSION: The newly introduced iAge, derived from inflammatory markers and telomere length, aligns with various metabolic dysfunctions and age-related disease risks, underscoring its potential ability in identifying aging-related phenotypes.

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Background: Evidence about the associations between Cantonese dietary patterns and mortality is scarce. We examined the prospective association of the dietary pattern with all-cause, cancer and cardiovascular disease (CVD) mortality in older Chinese. Methods: We included 19 598 participants of a Guangzhou Biobank cohort study aged 50+ years, who were recruited from 2003 to 2006 and followed up until July, 2022. The diet was assessed by using a 300-item validated food frequency questionnaire. The food items were collapsed into 27 food groups. Factor analysis (FA) was used to identify dietary patterns. Multivariable Cox regression produced hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Results: During 305 410 person-years, 4966 deaths including 1971 CVD, 1565 cancer and 1436 other-causes occurred. Four dietary patterns were identified by FA. No association of the vegetable-based dietary pattern with all-cause, CVD and cancer mortality was found. Compared with the lowest quartile of the healthy Cantonese dietary pattern score, the highest quartile showed lower risks of all-cause (HR 0.86, 95% CI 0.80-0.94) and CVD mortality (HR 0.84, 95% CI 0.72-0.97). The highest quartile of the nut and fruit dietary pattern showed lower risks of all-cause (HR 0.92, 95% CI 0.85-0.99) and CVD mortality (HR 0.82, 95% CI 0.72-0.93), while the unhealthy western dietary pattern was associated with a higher risk of all-cause (HR 1.10, 95% CI 1.01-1.19) and cerebrovascular disease mortality (HR 1.28, 95% CI 1.03-1.58). Conclusion: We have first identified four dietary patterns based on the Cantonese cuisine and found that healthy Cantonese and nut and fruit dietary patterns were associated with lower risks of all-cause and CVD mortality, whereas the unhealthy western dietary pattern was associated with a higher risk of all-cause and cerebrovascular disease mortality.

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PURPOSE: We examined the associations of soy product intake with all-cause, cardiovascular disease (CVD), and cancer mortality and mediations through CVD risk factors based on the Guangzhou Biobank Cohort Study (GBCS), and conducted updated meta-analyses. METHODS: A total of 29,825 participants aged 50 + years were included. Causes of death were identified through record linkage. Soy product intake was assessed by food frequency questionnaire. Cox proportional hazards regression was used to analyze the associations between soy product intake and mortality, yielding hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses with CVD risk factors as mediators, and updated meta-analyses were conducted. RESULTS: During 454,689 person-years of follow-up, 6899 deaths occurred, including 2694 CVD and 2236 cancer. Participants who consumed soy product of 1-6 portions/week, versus no consumption, had significantly lower risks of all-cause and CVD mortality (adjusted HR (95% CI) 0.91 (0.86, 0.97) and 0.87 (0.79, 0.96), respectively). In participants who consumed soy product of ≥ 7 portions/week, the association of higher intake with lower CVD mortality was modestly mediated by total cholesterol (4.2%, 95% CI 1.0-16.6%). Updated meta-analyses showed that the highest level of soy product intake, versus the lowest, was associated with lower risks of all-cause and CVD mortality (pooled HR (95% CI) 0.92 (0.88, 0.96) and 0.92 (0.87, 0.98), respectively). CONCLUSION: Moderate and high soy product intake were associated with lower risks of all-cause and CVD mortality. Our findings provide support for current dietary guidelines recommending moderate soy product intake, and contribute additional evidence regarding the potential protective effects of high soy product intake.

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BACKGROUND: The associations of high and low testosterone with all-cause and cardiovascular disease (CVD) mortality risk in men are conflicting. Our objective was to examine associations of total testosterone, free testosterone, bioavailable testosterone, and sex hormone-binding globulin (SHBG) with all-cause and CVD mortality in older Chinese men. METHODS: Total testosterone and SHBG were assayed, and free testosterone and bioavailable testosterone were calculated using Vermeulen formula. Cox proportional hazards regression was used to assess the associations with risks of all-cause and CVD mortality, giving hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Of 3 948 men aged 50+ years, 949 deaths (312 CVD) occurred during an average 10.5-year follow-up. After multivariable adjustments, the highest, versus the third, quartile of total testosterone and free testosterone were associated with higher all-cause mortality risk (1.17 [0.97-1.41] and 1.45 [1.20-1.74], respectively), whereas free testosterone was associated with higher CVD mortality risk (1.88 [1.33-2.66]). Similar positive associations were found for bioavailable testosterone and all-cause mortality risk (1.27 [1.05-1.54]). Lower SHBG (quartile 1 vs quartile 3) was associated with higher all-cause and CVD mortality risk (1.25 [1.04-1.52] and 1.28 [1.08-1.52], respectively). Consistent associations were observed in relatively healthy men and men excluded death during the first year. CONCLUSIONS: Higher total testosterone, free testosterone, and bioavailable testosterone were associated with higher all-cause mortality in older men, higher free testosterone was associated with higher CVD mortality whilst lower SHBG was associated with higher all-cause and CVD mortality. Clarification and confirmation of causality require further mechanistic studies.

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To examine the association of adverse childhood experiences (ACEs) with anemia among older people. 24,116 participants aged 50 years or above were recruited. Multivariable linear and logistic regression was used to assess the associations of self-reported ACEs number with hemoglobin concentrations (g/dL) and presence of anemia. Older individuals with two or more ACEs, versus no ACEs, showed lower hemoglobin concentrations (ß = - 0.08 g/dL, 95% confidence intervals (CI) - 0.12 to - 0.03) and higher odds of anemia (odds ratio = 1.26, 95% CI 1.01-1.59). A more pronounced association between ACEs and anemia in the lower education group was found, while the association became non-significant in those with higher education (P for ACEs-education interaction = 0.02). ACEs was associated with anemia in older people, and the association was stronger in those with lower education, highlighting the significance of early-life psychological stressors assessment and consideration of education background in geriatric care.

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BACKGRUOUND: Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis. METHODS: Participants (n=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk. RESULTS: During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies. CONCLUSION: Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.

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Social isolation has been found associated with multiple sleep traits in conventional observational studies. However, whether this association is causal and if so, its direction is uncertain. We analyzed the association between social isolation and multiple sleep traits in 30 430 participants from the Guangzhou Biobank Cohort Study. In bidirectional Mendelian randomization, we used 6, 17, and 11 single nucleotide polymorphisms associated with attendance at sports club/gym, religious group, and pub/social club from the UK Biobank (n = 452 302), respectively, and 152 single nucleotide polymorphisms associated with insomnia from the combination of UK Biobank and 23andme (n = 1 331 010). Observationally in the Guangzhou Biobank Cohort Study, insomnia (yes/no) (beta = 0.12, 95% confidence interval (CI) 0.10-0.16) and poor sleep quality (yes/no) (beta = 0.12, CI: 0.08-0.15), but not sleep duration and chronotype, were associated with a higher social isolation score (severe social isolation). In bidirectional MR, genetically predicted insomnia decreases the odds of attendance at sports club/gym (beta = 0.98, CI: 0.98-0.99) and religious groups (beta = 0.99, CI: 0.98-0.99), but not pub/social club. However, these 3 types of social activity were not associated with insomnia. Our results support the causal effects of insomnia on social activity. Further clinical investigations into the utility of insomnia treatment in alleviating social isolation are needed.

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