Association of life's essential 8 and asthma: mediating effect of inflammation and oxidative stress.

BACKGROUND: The association of cardiovascular health (CVH) with asthma risk in U.S. adults remains unclear. This study aimed to explore the association of Life's Essential 8 (LE8), a measurement of CVH, with asthma and investigate the potential mediating effect of inflammation and oxidative stress. METHODS: The data was obtained from the National Health and Nutrition Examination Survey (NHANES) in 2005-2018. LE8 score (range 0 ∼ 100) was measured and categorized as low (<50), moderate (50 ∼ <80), and high (≥80) CVH. Survey-weighted logistic regression and restricted cubic spline model were employed to explore the association between LE8 score and asthma. Mediation analyses were conducted to identify the mediating effects of inflammation and oxidative stress biomarkers. RESULTS: This study included 10,932 participants aged ≥ 20 years, among whom 890 (8.14%) reported prevalent asthma. After adjusting for all covariates, the odd ratios (OR) for asthma were 0.67 (95% confidence interval (CI): 0.48, 0.94) in the moderate CVH group and 0.52 (95% CI: 0.34, 0.79) in the high CVH group compared with the low CVH group, respectively. The OR for asthma was 0.85 (95% CI: 0.78, 0.93) for every 10 score increase in LE8 score, and linear dose-response relationship was observed (p = 0.0642). Mediation analyses showed that inflammation and oxidative stress mediated 15.97% and 11.50% of the association between LE8 score and asthma, respectively (all p < 0.05). CONCLUSIONS: LE8 score was negatively associated with asthma, and inflammation and oxidative stress partially mediated this association. It is recommended that maintaining optimal CVH may prevent asthma.

Causal effects of sleep traits on metabolic syndrome and its components: a Mendelian randomization study.

PURPOSE: Previous observational studies have suggested an association between sleep disturbance and metabolic syndrome (MetS). However, it remains unclear whether this association is causal. This study aims to investigate the causal effects of sleep-related traits on MetS using Mendelian randomization (MR). METHODS: Single-nucleotide polymorphisms strongly associated with daytime napping, insomnia, chronotype, short sleep, and long sleep were selected as genetic instruments from the corresponding genome-wide association studies (GWAS). Summary-level data for MetS were obtained from two independent GWAS datasets. Univariable and multivariable MR analyses were conducted to investigate and verify the causal effects of sleep traits on MetS. RESULTS: The univariable MR analysis demonstrated that genetically predicted daytime napping and insomnia were associated with increased risk of MetS in both discovery dataset (OR daytime napping = 1.630, 95% CI 1.273, 2.086; OR insomnia = 1.155, 95% CI 1.108, 1.204) and replication dataset (OR daytime napping = 1.325, 95% CI 1.131, 1.551; OR insomnia = 1.072, 95% CI 1.046, 1.099). For components, daytime napping was positively associated with triglycerides (beta = 0.383, 95% CI 0.160, 0.607) and waist circumference (beta = 0.383, 95% CI 0.184, 0.583). Insomnia was positively associated with hypertension (OR = 1.101, 95% CI 1.042, 1.162) and waist circumference (beta = 0.067, 95% CI 0.031, 0.104). The multivariable MR analysis indicated that the adverse effect of daytime napping and insomnia on MetS persisted after adjusting for BMI, smoking, drinking, and another sleep trait. CONCLUSION: Our study supported daytime napping and insomnia were potential causal factors for MetS characterized by central obesity, hypertension, or elevated triglycerides.

Investigating the shared genetic architecture between breast and ovarian cancers.

High heritability and strong correlation have been observed in breast and ovarian cancers. However, their shared genetic architecture remained unclear. Linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics (ρ-HESS) were applied to estimate heritability and genetic correlations. Bivariate causal mixture model (MiXeR) was used to qualify the polygenic overlap. Then, stratified-LDSC (S-LDSC) was used to identify tissue and cell type specificity. Meanwhile, the adaptive association test called MTaSPUsSet was performed to identify potential pleiotropic genes. The Single Nucleotide Polymorphisms (SNP) heritability was 13% for breast cancer and 5% for ovarian cancer. There was a significant genetic correlation between breast and ovarian cancers (rg=0.21). Breast and ovarian cancers exhibited polygenic overlap, sharing 0.4 K out 2.8 K of causal variants. Tissue and cell type specificity displayed significant enrichment in female breast mammary, uterus, kidney tissues, and adipose cell. Moreover, the 74 potential pleiotropic genes were identified between breast and ovarian cancers, which were related to the regulation of cell cycle and cell death. We quantified the shared genetic architecture between breast and ovarian cancers and shed light on the biological basis of the co-morbidity. Ultimately, these findings facilitated the understanding of disease etiology.

Identification of exosomes-related lncRNAs in clear cell renal cell carcinoma based on Bayesian spike-and-slab lasso approach.

Exosomes-related long non-coding RNAs (lncRNAs) have been reported to play significant roles in clear cell renal cell carcinoma (ccRCC). However, there is little known about the relationship between exosomes-related lncRNAs and ccRCC. This study aimed to select optimal prognostic model based on exosomes-related lncRNAs to provide a methodological reference for high-dimensional data. Based on the Cancer Genome Atlas (TCGA) database of 515 ccRCC patients, two risk score models were generated underlying Bayesian spike-and-slab lasso and lasso regression. The optimal model was determined by calculating the area of time-dependent receiver-operating characteristic (ROC) curves in the TCGA and ArrayExpress databases. The immune patterns and sensitivity of immunotherapy between the high and low groups were further explored. Initially, we constructed two risk score models containing 11 and 7 exosomes-related lncRNAs according to Bayesian spike-and-slab lasso and lasso regression respectively. ROC curves revealed that the model constructed by Bayesian spike-and-slab lasso regression was more reliable in predicting survival at 1, 3, and 5 years, yielding an area under the curves (AUCs) of 0.796, 0.732, and 0.742, respectively. Kaplan-Meier (K-M) curves presented that prognosis was poorer in the high-risk score group (P < 0.001). Additionally, the high-risk score group patients were enriched in immune-activating phenotypes and more sensitive to immunotherapy. The exosomes-related lncRNAs model constructed with Bayesian spike-and-slab lasso regression has higher predictive power for ccRCC patients' prognosis, which provides methodological reference for the analysis of high-dimensional data in bioinformatics and guides the tailored treatment of ccRCC patients.

Spatial distribution and driving factors of the associations between temperature and influenza-like illness in the United States: a time-stratified case-crossover study.

BACKGROUND: Several previous studies investigated the associations between temperature and influenza in a single city or region without a national picture. The attributable risk of influenza due to temperature and the corresponding driving factors were unclear. This study aimed to evaluate the spatial distribution characteristics of attributable risk of Influenza-like illness (ILI) caused by adverse temperatures and explore the related driving factors in the United States. METHODS: ILI, meteorological factors, and PM2.5 of 48 states in the United States were collected during 2011-2019. The time-stratified case-crossover design with a distributed lag non-linear model was carried out to evaluate the association between temperature and ILI at the state level. The multivariate meta-analysis was performed to obtain the combined effects at the national level. The attributable fraction (AF) was calculated to assess the ILI burden ascribed to adverse temperatures. The ordinary least square model (OLS), spatial lag model (SLM), and spatial error model (SEM) were utilized to identify driving factors. RESULTS: A total of 7,716,115 ILI cases were included in this study. Overall, the temperature was negatively associated with ILI risk, and lower temperature gave rise to a higher risk of ILI. AF ascribed to adverse temperatures differed across states, from 49.44% (95% eCI: 36.47% ~ 58.68%) in Montana to 6.51% (95% eCI: -6.49% ~ 16.46%) in Wisconsin. At the national level, 29.08% (95% eCI: 27.60% ~ 30.24%) of ILI was attributable to cold. Per 10,000 dollars increase in per-capita income was associated with the increment in AF (OLS: ß = -6.110, P = 0.021; SLM: ß = -5.496, P = 0.022; SEM: ß = -6.150, P = 0.022). CONCLUSION: The cold could enhance the risk of ILI and result in a considerable proportion of ILI disease burden. The ILI burden attributed to cold varied across states and was higher in those states with lower economic status. Targeted prevention programs should be considered to lower the burden of influenza.

Endoscopic retrograde appendicitis therapy versus laparoscopic appendectomy for uncomplicated acute appendicitis.

BACKGROUND: Endoscopic retrograde appendicitis therapy (ERAT) is a new and minimally invasive technique for the treatment of acute appendicitis. This study aimed to assess the efficacy and clinical outcomes of ERAT versus laparoscopic appendectomy for patients with uncomplicated acute appendicitis. METHODS: We adopted propensity score matching (1:1) to compare ERAT and laparoscopic appendectomy in patients with uncomplicated acute appendicitis between April 2017 and March 2020. We reviewed 2880 patients with suspected acute appendicitis, of whom 422 patients with uncomplicated acute appendicitis met the matching criteria (ERAT 79; laparoscopic appendectomy 343), yielding 78 pairs of patients. RESULTS: The rate of curative treatment within 1 year after ERAT was 92.1 % (95 % confidence interval [CI] 83.8 % to 96.3 %). The percentage of patients recording visual analog scale values of  ≤ 3 for pain at 6 hours after treatment was 94.7 % (95 %CI 87.2 % to 97.9 %) in the ERAT group, which was significantly higher than that in the laparoscopic appendectomy group (83.3 %; 95 %CI 73.5 % to 90.0 %). Median procedure time and median hospital length of stay were significantly lower in the ERAT group compared with the laparoscopic appendectomy group. At 1 year, the median recurrence time was 50 days (interquartile range 25-127) in the ERAT group. The overall adverse event rate was 24.4 % (95 %CI 14.8 % to 33.9 %) in the laparoscopic appendectomy group and 18.4 % (95 %CI 9.7 % to 27.1 %) in the ERAT group, with no significant difference between the two groups. CONCLUSION: ERAT was a technically feasible method of treating uncomplicated acute appendicitis compared with laparoscopic appendectomy.

Trends and influence factors in the prevalence, intervention, and control of metabolic syndrome among US adults, 1999-2018.

AIM: We aimed to describe the trends in the prevalence, intervention, and control of metabolic syndrome (MetS) among US adults through 1999-2018. Additionally, the influence factors of MetS and its control were further explored. METHODS: We included participants older than 20 using the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 (n = 22,114). The rate of prevalence, intervention, and control of MetS were caculated by survey weights. Joinpoint regression and survey-weighted generalized linear models were used to analyze trends and influence factors, respectively. RESULTS: The prevalence of MetS increased from 28.23 to 37.09% during 1999-2018 (P for trend < 0.05). The former smoker (OR = 1.20, 95%CI: 1.07, 1.36) and current smoker (OR = 1.27, 95%CI: 1.11, 1.45) increased the prevalence of MetS. While vigorous activity (OR = 0.53, 95%CI: 0.47, 0.61) decreased it. Among MetS components, the prevalence of elevated blood-glucose (from 21.18 to 34.68%) and obesity (from 44.81 to 59.06%) raised (P for trend < 0.05), with an uptrend in the use of antidiabetic (from 9.87 to 28.63%) and a downtrend of vigorous activity (from 23.79 to 16.53%) (P for trend < 0.05). Decreased trends were observed in the control of Hb1Ac (< 7%) (from 87.13 to 84.06%) and BMI (<25 kg/m2) (from 11.36 to 7.49%). Among MetS underwent antidiabetic, 45-64 years old and male decreased the control of Hb1Ac (< 7%). The control of BMI (<25 kg/m2) among individuals with physical activity was reduced mainly in the population of younger (aged 20-44 years old), male, non-Hispanic black, middle income and smoker (former and current). CONCLUSIONS: The prevalence of MetS increased significantly through 1999-2018. Elevated blood glucose and obesity were the main causes of MetS burden. Quitting smoking and increasing physical activity may decrease the prevalence of MetS. In the control of blood-glucose and obesity, we should screen out the focus population to modify treatment and improve lifestyle.

Change in the global burden of depression from 1990-2019 and its prediction for 2030.

OBJECTIVE: Depression is a global health challenge, but only a few studies have fully assessed and predicted the disease burden. This study described the trend of global depression burden from 1990 to 2019 through age-standardized incidence rate (ASIR), age-standardized disability-adjusted life rate (ASDR), and predicted the number of cases of depression during 2020-2030. METHODS: Linear regression analysis was used to calculate the estimated annual percentage change (EAPC) in the age-standardized rates. The trends of global depression burden from 1990 to 2019 were analyzed by age, sex, and socio-demographic index (SDI) across various regions. Finally, we used the Bayesian age-period-cohort (BAPC) model to predict the disease burden in the coming 10 years. RESULTS: Globally, the ASIR of depression decreased from 3681.24 per 100,000 population in 1990 to 3588.25 per 100,000 population in 2019 and the EAPC was -0.29%. ASDR also decreased, following a similar trend as the ASIR. The highest ASDR was observed in adults aged 60-64 years. The burden of depressive illness was higher in women, with the greatest increase in incidence in low SDI areas. BAPC predicted that the worldwide ASIR and ASDR of depression would stabilize from 2020 to 2030, with an increasing number of cases. By 2030, the ASIR was estimated to be 2519.88 per 100,000 men and 3835.11 per 100,000 women. CONCLUSION: From 1990 to 2019, the global burden of depression remained significant, especially among women. It is important to address depression in older people, and it is therefore necessary to develop measures for prevention.

Causal association of rheumatoid arthritis with frailty and the mediation role of inflammatory cytokines: A Mendelian randomization study.

BACKGROUND: Previous observational studies have suggested the association between rheumatoid arthritis (RA) and frailty. However, it remains obscure whether this association is causal. This study aims to investigate the causal association of RA with frailty and the mediation effect of inflammatory cytokines using Mendelian randomization (MR) design. METHODS: Summary-level data for RA (N = 58,284), frailty index (FI) (N = 175,226), Fried frailty score (FFS) (N = 386,565), and 41 inflammatory cytokines (N = 8,293) were obtained from recent genome-wide association studies. Univariable and multivariable MR analyses were conducted to investigate and verify the causal association of RA with frailty. The potential mediation effects of inflammatory cytokines were estimated using two-step MR. RESULTS: Univariable inverse variance weighted MR analysis suggested that genetically determined RA was associated with increased FI (beta=0.021; 95 % CI: 0.012, 0.03; p = 2.2 × 10-6) and FFS (beta=0.011; 95 %CI: 0.007, 0.015; p = 8.811 × 10-8). The consistent results were observed in multivariable MR analysis after adjustment for asthma, smoking, BMI, physical activity, telomere length, and depression. Mediation analysis showed evidence of an indirect effect of RA on FI through monokine induced by interferon-gamma (MIG) with a mediated proportion of 9.8 % (95 %CI: 4.76 %, 19.05 %), on FFS via MIG and stromal cell-derived factor-1 alpha with a mediated proportion of 9.6 % (95 %CI: 0 %, 18.18 %) and 8.44 % (95 %CI: 0 %, 18.18 %), respectively. CONCLUSION: This study provided credible evidence that genetically predicted RA was associated with a higher risk of frailty. Additionally, inflammatory cytokines were involved in the mechanism of RA-induced frailty.

Metabolic score and its components are associated with carotid plaque prevalence in young adults.

PURPOSE: No study has comprehensively assessed the relationship of metabolic factors including insulin resistance, hypertension, hyperuricemia, and hypercholesterolemia with the development of carotid plaque. Therefore, we constructed metabolic scores based on the above metabolic factors and examined its association with carotid plaque in young and older Chinese adults. METHODS: This study included 17,396 participants who underwent carotid ultrasound examinations, including 14,173 young adults (<65 years) and 3,223 older adults (≥65 years). Individual metabolic score was calculated using triglyceride-glucose (TyG) index, mean arterial pressure (MAP), uric acid, and total cholesterol (TC). Logistic regression models were conducted to examine the role of metabolic score and its components in the prevalence of carotid plaque. The nonlinear relationship was examined using restricted cubic spline regression. Meanwhile, subgroup, interaction, and sensitivity analyses were conducted. RESULTS: The multivariate logistic regression analysis showed that TyG (OR: 1.088; 95%CI: 1.046-1.132), MAP (OR: 1.121; 95%CI: 1.077-1.168), TC (OR: 1.137; 95%CI: 1.094-1.182) and metabolic score (OR: 1.064; 95%CI: 1.046-1.082) were associated with carotid plaque prevalence in young adults rather than older adults. The nonlinear association was not observed for metabolic scores and carotid plaque. Subgroup analyses showed significant associations between metabolic scores and carotid plaque prevalence in men, women, normal-weight, and overweight young adults. No interaction of metabolic score with sex and BMI were observed. CONCLUSIONS: The results support that control of TyG, MAP, TC, and metabolic scores is a key point in preventing the prevalence of carotid plaque in the young adults.

Impact of weekday of esophageal cancer surgery on long-term oncological outcomes.

BACKGROUND: Studies about the influence of weekday of esophagectomy on survival are limited and show conflicting results. This study aimed to explore whether weekday of esophagectomy affects patient's survival outcomes. METHODS: Patients who underwent esophagectomy in a grade-A tertiary hospital from January 2015 to December 2016 were enrolled. The primary outcome was 5-year overall survival (OS). The secondary outcomes were 5-year disease-free survival (DFS) and days of hospitalization. The impact of weekday surgery on 5-year OS and DFS were evaluated with Cox regression, and impact on days of hospitalization was assessed using logistic regression. Propensity score matching (PSM) analysis was used to balance the confounding factors. RESULTS: A total of 1478 patients were included. The 5-year OS and DFS were 63.77% and 59.26% respectively. Multivariate analyses adjusted for covariables indicated that weekday was not significantly associated with OS (P = 0.076), nor days of hospitalization (P = 0.824), but it appeared to be associated with DFS (P = 0.044). Additionally, PSM analysis showed no significant effect of weekday on the 5-year OS, nor DFS and days of hospitalization. CONCLUSION: In patients diagnosed with squamous esophageal cancer, the survival outcome of patients was not influenced by weekday.

Effects of intra- and inter-day temperature change on acute upper respiratory infections among college students, assessments of three temperature change indicators.

Background: Acute upper respiratory infection (AURI) is a significant disease affecting all age groups worldwide. The differences in the impacts of different temperature change indicators, such as diurnal temperature range (DTR), temperature variation (TV), and temperature change between neighboring days (TCN), on AURI morbidity, are not clear. Methods: We collected data on 87,186 AURI patients during 2014-2019 in Zhengzhou. Distributed lag non-linear model was adopted to examine the effects of different temperature change indicators on AURI. We calculated and compared the attributable fractions (AF) of AURI morbidity caused by various indicators. We used stratified analysis to investigate the modification effects of season and gender. Results: With the increase in DTR and TV, the risk of AURI tended to increase; the corresponding AF values (95% eCI) higher than the references (5% position of the DTR or TV distribution) were 24.26% (15.46%, 32.05%), 23.10% (15.59%, 29.20%), and 19.24% (13.90%, 24.63%) for DTR, TV0 - 1, and TV0 - 7, respectively. The harmful effects of TCN on AURI mainly occurred when the temperature dropped (TCN < 0), and the AF value of TCN below the reference (0°C) was 3.42% (1.60%, 5.14%). The harm of DTR and TV were statistically significant in spring, autumn and winter, but not in summer, while the harm of TCN mainly occurred in winter. Three indicators have statistically significant effects on both males and females. Conclusions: High DTR and TV may induce AURI morbidity, while the harm of TCN occurs when the temperature drops. The impacts of DTR and TV on AURI are higher than that of TCN, and the impact of few-day TV is higher than that of multi-day TV. The adverse effects of DTR and TV are significant except in summer, while the hazards of TCN mainly occur in winter.

Combined effects of genetic predisposition and sleep quality on acceleration of biological ageing: Findings from the UK biobank cohort.

OBJECTIVE: Genetic risks can accelerate ageing, yet better quality sleep may slow down it. We thus examined the interaction and combined effects of genetic predisposition and sleep quality on the risk of accelerate aging. METHODS: This study included 407,027 participants from the UK Biobank. Sleep index of each participant was retrieved from the following seven sleep behaviors: snoring, chronotype, daytime sleepiness, sleep duration, insomnia, nap and difficulties in getting up. The biological age (PhenoAge) were estimated by corresponding algorithms based on clinical traits, and their residual discrepancies with chronological age were defined as the age accelerations (PhenoAgeaccel). We explored the interaction and combined effects of genetic risk and sleep quality on accelerated ageing by constructing a linear model. RESULTS: Compared with participants in low sleep quality group, those in medium and high sleep quality group decreased 0.727 (95%CI, 0.653 to 0.801) and 1.056 (95%CI, 0.982 to 1.130) years of PhenoAgeaccel, respectively. Compared with participants in low genetic risk group, those in medium and high genetic risk group increased 0.833 (95%CI, 0.792 to 0.874) and 1.543 (95%CI, 1.494 to 1.592) years of PhenoAgeaccel, respectively. There was interaction between the genetic risk and sleep quality (P-interaction<0.001). For combined effect, compared to the group with high sleep quality and lower genetic risk, people with low sleep quality and high genetic risk had 2.747 (95%CI, 2.602 to 2.892) years higher PhenoAgeaccel. CONCLUSION: Our findings elucidate that better sleep quality could lessen accelerated biological ageing especially among population with high genetic risk.

Mining of adverse event signals associated with inclisiran: a post-marketing analysis based on FAERS.

BACKGROUND: This study analyzed adverse events (AEs) associated with inclisiran using the FDA's Adverse Event Reporting System (FAERS) to detect and characterize relevant safety signals. METHODS: We retrospectively extracted AE reports from the FAERS database spanning Q1 2022 to Q2 2024. Four disproportionality analysis algorithms were employed to identify AE signals for inclisiran, with subsequent comparisons made to PCSK9 monoclonal antibodies (alirocumab/evolocumab). Additionally, we examined the characteristics and onset timing of inclisiran-related AE. RESULTS: A total of 4,122 reports of inclisiran as the 'primary suspected'. Compared with all other drugs, the most significant system organ class (SOC) was 'musculoskeletal and connective tissue disorders' (ROR = 3.64, PRR = 3.19) and the most common SOC was 'general disorders and administration site conditions' (n = 2,769). These two SOCs were more strongly with inclisiran than evolocumab. At the preferred term level, strong signals were detected for cellulitis gangrenous (ROR = 101.29, PRR = 101.27, IC = 6.54, EBGM = 92.91) and bladder discomfort (ROR = 12.61, PRR = 12.61, IC = 3.64, EBGM = 12.48). The median onset time for inclisiran-related AEs was 43 days (interquartile range: 7-99 days). CONCLUSIONS: This study enhanced our understanding of AEs to inclisiran. Future research on its long-term real-world use will offer insights into its safety.

Associations of Dietary Diversity Trajectories with Frailty among Chinese Older Adults: A Latent Class Trajectory Analysis Based on a CLHLS Cohort.

BACKGROUND: High dietary diversity has been found to be associated with frailty. However, the trajectory of dietary diversity intake in relation to frailty is unclear. METHODS: Using the latent class trajectory modeling approach, we identified distinctive dietary variety trajectory groups among 2017 participants based on the Chinese Longitudinal Healthy Longevity Survey acquired at four time points within a 10-year period. Frailty status was assessed using a frailty index comprising 37 health deficits. Dietary diversity was quantified using the dietary variety score (DVS), based on food category consumption frequency. Logistic regression analyses were employed to explore the association between DVS change trajectories and frailty. RESULTS: This study identified two distinct DVS trajectories: "Moderate-Slow decline-Slow growth", encompassing 810 (40.16%) individuals, and "Moderate-Slow growth-Accelerated decline", including 1207 (59.84%) individuals. After adjusting for covariates, the odds ratio for DVS in the "Moderate-Slow decline-Slow growth" group was 1.326 (95% confidence interval: 1.075-1.636) compared to the "Moderate-Slow growth-Accelerated decline" group. The "Moderate-Slow decline-Slow growth" trajectory continued to decrease and was maintained at a low level in the early stages of aging. CONCLUSION: Sustaining a high dietary diversity trajectory over time, particularly in the early stages of aging, could potentially decrease the risk of frailty among older Chinese adults.

Associations between physical activity and all-cause and cardiovascular mortality in adults with type 2 diabetes mellitus: A prospective cohort study from NHANES 2007-2018.

AIMS: To investigate the dose-response association between physical activity and all-cause and cardiovascular mortality in adults with type 2 diabetes mellitus and the effects of replacing sedentary behavior with physical activity. METHODS: 4808 adults with type 2 diabetes mellitus were included in NHANES 2007-2018. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals. Isotemporal substitution analyses were further to determine the possible benefit of replacing sedentary time. RESULTS: During a median follow-up of 6.58 years, 902 deaths occurred, including 290 deaths from cardiovascular disease. Compared with the inactive group, the low-active and high-active groups were associated with declined risks of all-cause mortality [HRs (95% CIs) 0.64 (0.50, 0.83); 0.60 (0.50, 0.73), respectively] and cardiovascular mortality [0.50 (0.29, 0.88); 0.54 (0.39, 0.76)), respectively]. Dose-response analysis showed a significant U-shaped curve between physical activity and all-cause and cardiovascular mortality. Replacing 30 min/day of sedentary time with physical activity was substantially linked to a reduced risk of 8-32% mortality. CONCLUSION: A high level of PA of 40.52 and 31.66 MET-h/week was respectively related to the lowest risk of all-cause and cardiovascular mortality. Replacing sedentary time with physical activity could benefit the type 2 diabetes mellitus population.

Effect of Maternal Pre-Pregnancy Body Mass Index on Longitudinal Fetal Growth and Mediating Role of Maternal Fasting Plasma Glucose: A Retrospective Cohort Study.

Purpose: To assess the impact of maternal pre-pregnancy body mass index (BMI) on longitudinal fetal growth, and the potential mediation effect of the maternal fasting plasma glucose in first trimester. Methods: In this retrospective cohort study, we collected pre-pregnancy BMI data and ultrasound measurements during pregnancy of 3879 singleton pregnant women who underwent antenatal examinations and delivered at Peking Union Medical College Hospital. Generalized estimation equations, linear regression, and logistic regression were used to examine the association between pre-pregnancy BMI with fetal growth and adverse neonatal outcomes. Mediation analyses were also used to examine the mediating role of maternal fasting plasma glucose (FPG) in first trimester. Results: A per 1 Kg/m² increase in pre-pregnancy BMI was associated with increase fetal body length Z-score (ß 0.010, 95% CI 0.001, 0.019) and fetal body weight (ß 0.017, 95% CI 0.008, 0.027). In mid pregnancy, pre-pregnancy BMI also correlated with an increase Z-score of fetal abdominal circumference, femur length (FL). Pre-pregnancy BMI was associated with an increased risk of large for gestational age and macrosomia. Mediation analysis indicated that the associations between pre-pregnancy BMI and fetal weight in mid and late pregnancy, and at birth were partially mediated by maternal FPG in first trimester (mediation proportion: 5.0%, 8.3%, 1.6%, respectively). Conclusion: Maternal pre-pregnancy BMI was associated with the longitudinal fetal growth, and the association was partly driven by maternal FPG in first trimester. The study emphasized the importance of identifying and managing mothers with higher pre-pregnancy BMI to prevent fetal overgrowth.

Mining of neurological adverse events associated with valbenazine: A post-marketing analysis based on FDA adverse event reporting system.

PURPOSE: Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate neurological safety signals associated with valbenazine. METHODS: Data was collected in FAERS from the second quarter of 2017 to the fourth quarter of 2023 for data cleaning. Neurological adverse event (AE) signals of valbenazine were mined by calculating reporting odds ratios (ROR), information component (IC) and empirical Bayesian geometric mean (EBGM). The serious and non-serious cases and signals were prioritized using a rating scale. RESULTS: The number of neurological AE reports where the primary suspect (PS) drug was 8981 for valbenazine. Significant AE signals were identified by the preferred term (PT) analysis for valbenazine, including somnolence (ROR 19.69), tremor (ROR 15.17), and tardive dyskinesia (ROR 236.91), among which 18 AEs were identified as new signals. Patient age (p < 0.009) and sex (p = 0.197) might be associated with an increased risk of neurological AE severity. Notably, the association between valbenazine and neurological disorders remained when stratified by sex, age, and reporter type. AE timing analysis was performed for the drug and four moderate clinical priority signals [i.e., somnolence, balance disorder, parkinsonism, and akathisia (priorities 7)], showing the same early failure type profiles. CONCLUSIONS: The increase in neurological safety signals is identified in the post-marketing research of valbenazine. Clinicians need to pay attention to not only common AEs but also be alert to new neurological AE signals when using valbenazine.

A randomized, blind, parallel controlled phase I clinical trial to evaluate the safety and preliminary immunogenicity of 23-valent pneumococcal polysaccharide vaccine in healthy people aged 2 years and older.

BACKGROUND: Despite some progress in pneumococcal immunization, the global burden of pneumococcal infection remains high, and pneumococcal disease remains a public health concern. Studies in China and abroad have found that 23-valent pneumococcal polysaccharide vaccine (PPV23) vaccination can effectively prevent invasive pneumococcal disease. This phase Ⅰ clinical study assessed the safety and immunogenicity of a PPV23 vaccine candidate. METHODS: All subjects were randomly assigned to receive one dose intramuscular injection of experimental vaccine or control vaccine at a ratio of 1:1. The incidence of any adverse events was observed within 30 min, 0-7 days and 8-28 days post vaccination and the incidence of abnormal blood biochemical and blood routine indicators were tested on the 4th day post vaccination, the incidence of serious adverse events (SAEs) at 6 months post vaccination was recorded. Blood samples were collected prior to vaccination and on the 28th day post vaccination, and serum antibodies were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: The most common adverse reaction was pain at the injection site, followed by erythema. There was no significant difference of the incidence of systemic adverse reactions between the two vaccine groups. The adverse reactions observed in the trial were all common vaccination-related reactions, and no serious adverse reactions were observed. Compared to pre-vaccination, the (geometric mean concentrations) GMCs of IgG (immunoglobulin G) specific antibody against each serotype were all increased in the experimental group and the control group, there were statistical differences in seroconversion rates of serotypes 4 and 20 between the two vaccine groups. CONCLUSION: This clinical study showed good safety of the PPV23 vaccine candidate produced by Ab&b Biotechnology Co., Ltd.JS had good safety after vaccination in people aged 2 years and older. At the same time, good immunogenicity was also demonstrated.

Birth Weight, Cardiometabolic Factors, and Coronary Heart Disease: A Mendelian Randomization Study.

CONTEXT: Observational studies have shown associations of birth weight (BW) with coronary heart disease (CHD), but results are inconsistent and do not distinguish the fetal or maternal effect of BW. OBJECTIVE: This study aims to explore the causal association between BW and CHD, analyze the fetal and maternal contribution, and quantify mediating effects of cardiometabolic factors. METHODS: Genetic variants from genome-wide association study summary-level data of own BW (N = 298 142), offspring BW (N = 210 267 mothers), and 16 cardiometabolic (anthropometric, glycemic, lipidemic, and blood pressure) factors were extracted as instrumental variables. We used two-sample Mendelian randomization study (MR) to estimate the causal effect of BW on CHD (60 801 cases and 123 504 controls from mixed ancestry) and explore the fetal and maternal contributions. Mediation analyses were conducted to analyze the potential mediating effects of 16 cardiometabolic factors using two-step MR. RESULTS: Inverse variance weighted analysis showed that lower BW raised the CHD risk (ß -.30; 95% CI: -0.40, -0.20) and consistent results were observed in fetal-specific/maternal-specific BW. We identified 5 mediators in the causal pathway from BW to CHD, including body mass index-adjusted hip circumference, triglycerides, fasting insulin, diastolic blood pressure, and systolic blood pressure (SBP), with mediated proportion ranging from 7.44% for triglycerides to 27.75% for SBP. Causality between fetal-specific and maternal-specific BW and CHD was mediated by glycemic factors and SBP, respectively. CONCLUSION: Our findings supported that lower BW increased CHD risk and revealed that fetal-specific and maternal-specific BW may both contribute to this effect. The causality between BW and CHD was mediated by several cardiometabolic factors.