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.

Association between cardiorespiratory fitness and risk of all-cause and cause-specific mortality.

OBJECTIVE: The association of cardiorespiratory fitness (CRF) with all-cause and cause-specific mortality remains unclear in Chinese population. This study aimed to evaluate the risk of all-cause, cardiovascular disease (CVD), cancer and other-cause mortality in Chinese adults using estimated CRF (eCRF). PATIENTS AND METHODS: We analysed data for 15,566 participants aged ≥20 years recruited in The Rural Chinese Cohort Study during 2007 to 2008 and followed for mortality during 2013 to 2014. eCRF was calculated with sex-specific longitudinal non-exercise algorithms. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality risk according to baseline eCRF. RESULTS: During a median of 6.01 years of follow-up, 859 deaths occurred, including 359 from CVD, 221 from cancer, and 279 from other causes. Each 1 metabolic equivalent increment in eCRF was associated with decreased risk of all-cause mortality (men: HR 0.70, 95% CI [0.66-0.74]; women: 0.59, [0.54-0.64]); CVD mortality (men: 0.70 [0.64-0.77]; women: 0.55, [0.48-0.62]); and other-cause mortality (men: 0.68 [0.62-0.75]; women: 0.57, [0.49-0.66]). The area under receiver operating characteristic curve was significantly higher for eCRF than its modifiable components (waist circumference, body mass index and resting heart rate) in predicting all-cause and cause-specific mortality incidence (all p < .001). CONCLUSION: eCRF was inversely associated with all-cause, CVD and other-cause mortality.

Comparison of six surrogate insulin resistance indexes for predicting the risk of incident stroke: The Rural Chinese Cohort Study.

BACKGROUND AND PURPOSE: Some cheap and easily used operated indexes of insulin resistance (IR) were currently available. We aimed to evaluate the association of six surrogate indexes of IR with incident stroke and to compare their predictive capacity. METHODS: We analysed data from 14,595 eligible study participants from the Rural Chinese Cohort Study. Modified Poisson regression models were used to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) of incident stroke associated with the visceral adiposity index (VAI), the Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), triglyceride-glucose (TyG), TyG-body mass index, and TyG-waist circumference. The receiver operator characteristic curve was used to compare the ability of the abovementioned IR indexes to predict stroke. RESULTS: During a median follow-up of 6 years, 786 newly diagnosed stroke cases were identified. The levels of six surrogate indexes of IR were all significantly higher in the stroke population than in the non-stroke population (p < 0.001). Compared with quartile 1, the multivariable adjusted RRs (95% CIs) of incident stroke for quartile 4 were 2.01 (1.47-2.76), 1.62 (1.28, 2.04), 1.64 (1.28-2.09), and 1.92 (1.50-2.45) for CVAI, VAI, LAP, and TyG, respectively. Significant dose-response associations were also found between surrogate IR indexes and risk of stroke. The area under the curves|areas under the curves for CVAI (0.674) was significantly greater than for other indexes (TyG-WC:0.622, TyG:0.614, LAP:0.606, TyG-BMI:0.598, and VAI:0.577) (p < 0.001). CONCLUSIONS: Six surrogate indexes of IR were independently associated with incident stroke. The CVAI may be the most suitable index for stroke prediction.

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.

Cardiorespiratory fitness and mortality from all causes, cardiovascular disease and cancer: dose-response meta-analysis of cohort studies.

OBJECTIVE: Current evidence of the associations between cardiorespiratory fitness (CRF) and mortality is limited. We performed a meta-analysis to assess the dose-response association of CRF with mortality from all causes, cardiovascular disease (CVD) and cancer in healthy population. METHODS: PubMed, EMBASE and Web of Science were searched up to 26 December 2019 for reports of cohort studies giving risk estimates for all-cause, CVD and cancer mortality by level of CRF. Cohort studies were included if CRF was assessed by an exercise stress test and reported as at least three levels or per incremental increase, and the association of CRF with all-cause, CVD and cancer mortality was evaluated. Generalised least-squares regression models were used to assess the quantitative relation of CRF with all-cause, CVD and cancer mortality. RESULTS: 34 cohort studies were eligible for the meta-analysis. The pooled relative risks (RRs) for all-cause, CVD and cancer mortality per one-metabolic equivalent increase in CRF were 0.88 (95% CI 0.83 to 0.93), 0.87 (95% CI0.83 to 0.91) and 0.93 (95% CI 0.91 to 0.96), respectively. As compared with lowest CRF, with intermediate CRF, the summary RRs for all-cause, CVD and cancer mortality were 0.67 (95% CI 0.61 to 0.74), 0.60 (95% CI 0.51 to 0.69) and 0.76 (95% CI 0.69 to 0.84), respectively, and with highest CRF were 0.47 (95% CI 0.39 to 0.56), 0.49 (95% CI 0.42 to 0.56) and 0.57 (95% CI 0.46 to 0.70), respectively. CONCLUSION: Our analysis showed inverse dose-response associations of CRF with all-cause, CVD and cancer mortality, which provides evidence for public health recommendations for preventing all-cause, CVD and cancer mortality. PROSPERO REGISTRATION NUMBER: CRD42020208883.

Current Sample Preparation Methodologies for Determination of Catecholamines and Their Metabolites.

Catecholamines (CAs) and their metabolites play significant roles in many physiological processes. Changes in CAs concentration in vivo can serve as potential indicators for the diagnosis of several diseases such as pheochromocytoma and paraganglioma. Thus, the accurate quantification of CAs and their metabolites in biological samples is quite important and has attracted great research interest. However, due to their extremely low concentrations and numerous co-existing biological interferences, direct analysis of these endogenous compounds often suffers from severe difficulties. Employing suitable sample preparation techniques before instrument detection to enrich the target analytes and remove the interferences is a practicable and straightforward approach. To date, many sample preparation techniques such as solid-phase extraction (SPE), and liquid-liquid extraction (LLE) have been utilized to extract CAs and their metabolites from various biological samples. More recently, several modern techniques such as solid-phase microextraction (SPME), liquid-liquid microextraction (LLME), dispersive solid-phase extraction (DSPE), and chemical derivatizations have also been used with certain advanced features of automation and miniaturization. There are no review articles with the emphasis on sample preparations for the determination of catecholamine neurotransmitters in biological samples. Thus, this review aims to summarize recent progress and advances from 2015 to 2021, with emphasis on the sample preparation techniques combined with separation-based detection methods such capillary electrophoresis (CE) or liquid chromatography (LC) with various detectors. The current review manuscript would be helpful for the researchers with their research interests in diagnostic analysis and biological systems to choose suitable sample pretreatment and detection methods.

Novel common variants associated with body mass index and coronary artery disease detected using a pleiotropic cFDR method.

Genome-wide association studies (GWAS) have been successfully applied in identifying single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) and coronary heart disease (CAD). However, the SNPs to date can only explain a small percentage of the genetic variances of traits. Here, we applied a genetic pleiotropic conditional false discovery rate (cFDR) method that combines summary statistic p values from different multi-center GWAS datasets, to detect common genetic variants associated with these two traits. The enrichment of SNPs associated with BMI and CAD was assessed by conditional Q-Q plots and the common variants were identified by the cFDR method. By applying the cFDR level of 0.05, 7 variants were identified to be associated with CAD (2 variants being novel), 34 variants associated with BMI (11 variants being novel), and 3 variants associated with both BMI and CAD (2 variants being novel). The SNP rs653178 (ATXN2) is noteworthy as this variant was replicated in an independent analysis. SNP rs12411886 (CNNM2) and rs794356 (HIP1) were of note as the annotated genes may be associated with processes that are functionally important in lipid metabolism. In conclusion, the cFDR method identified novel variants associated with BMI and/or CAD by effectively incorporating different GWAS datasets.

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.

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.

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.

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 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.

Conveniently monitoring aldehyde changes in heated edible oils using miniaturized kapok fiber-supported liquid-phase extraction/in-situ derivatization coupled with liquid chromatography-tandem mass spectrometry.

Heating edible oils generates aldehydes, potentially leading to adverse health effects, making their analysis essential for quality control. This study presents a convenient miniaturized kapok fiber-supported liquid-phase extraction/in-situ derivatization method for the simultaneous extraction and derivatization of aldehydes in oils. The method involves placing 150 mg oil into a 1 mL pipette tip packed with 25 mg kapok fiber, adding 150 µL ACN with 1.5 mg mL-1 DNPH, and post 30-minute static extraction, retrieving the extractant with a pipettor for liquid chromatography-tandem mass spectrometry analysis. By optimizing critical parameters through a Box-Behnken design, the method exhibits good linearity (1-500 ng g-1, R2 ≥ 0.991), low detection limits (0.2-1.0 ng g-1), excellent accuracy (95.3-107.1%) and high precisions (relative standard deviation < 7.9%). This method simplifies sample preparation processes, cuts solvent use, and facilitates automation. It effectively identifies ten aldehyde variations in six heated oils, displaying distinct profiles consistent with prior research.

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.