Threshold effect of physical exercise on its association to diabetes mellitus in short sleep population: evidence from a nationwide study.

Background: The prevalence of diabetes mellitus (DM) is a significant public health concern, especially among individuals with short sleep duration. Understanding the relationship between physical exercise and DM in this population is crucial for developing effective prevention strategies. However, the presence of a potential threshold effect of exercise on DM risk remains unclear. Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018, this population-based study investigated the association between physical exercise and DM in individuals with short sleep duration (no more than 7 hours per night). Weighted logistic regression analyses were conducted, adjusting for demographic and lifestyle factors. Additionally, a two-piecewise linear regression model was employed to identify any threshold effect of exercise on DM risk. Results: This study included 15,092 participants identified with short sleep duration. Demographic characteristics stratified by DM status indicate higher prevalence among certain groups, such as middle-aged and older adults, males, and non-Hispanic Whites. The analysis revealed an inverse association between exercise levels and DM prevalence among the short sleep population. In the fully adjusted model, individuals engaging in sufficient exercise (> 600 MET-minutes/week) exhibited significantly reduced odds of developing DM [OR (95% CI): 0.624(0.527,0.738), p < 0.001]. Furthermore, the segmented regression model identified an inflection point at 2000 MET-minutes/week, below which a significant correlation between exercise and DM was observed. Conclusions: This study provides evidence of a threshold effect of physical exercise on its association with DM in individuals with short sleep duration. Tailored exercise interventions targeting this population may help mitigate DM risk and improve overall health outcomes. Further research is warranted to validate these findings and explore optimal exercise thresholds for DM prevention strategies.

Saturation effects of the relationship between physical exercise and systemic immune inflammation index in the short-sleep population: a cross-sectional study.

BACKGROUND: Short sleep can lead to an increase in inflammation and regular exercise has been shown to have a mitigation effect. However, the association between physical exercise (PE) and inflammation in the short sleep population is an unknown and intriguing issue. METHODS: NHANES dataset spanning the years 2007 to 2018 were analyzed. To investigate the relationship mentioned above, we carried out multivariate linear regression models controlling for sociodemographic and lifestyles factors. The systemic immune inflammation index (SII) served as a reflection of inflammatory potential, calculated as the product of platelet count, neutrophil count, and divided by the lymphocyte count. Self-reported questionnaires were used to collect sleep and exercise information. RESULTS: A total of 14,664 participants were included for final analysis. Across the three models, PE showed significant negative associations with SII as a continuous variable [Crude Model, ß (95% CI): -1.261(-1.600, -0.922), p < 0.001; Model 1, ß (95% CI): -1.005(-1.344, -0.666), p < 0.001; Model 2, ß (95% CI): -0.470(-0.827, -0.112), p = 0.011]. The consistent nature of the findings persisted when investigating physical exercise (PE) as a categorized variable. By two-piecewise linear regression model, we calculated a saturation effect of PE with the inflection point as 2400 MET-minutes/week. CONCLUSION: This study suggested that performing no more than 2400 MET-minutes/week of PE was associated with lower SII levels in the short sleep population, while more PE might not bring additional benefits.

Exploring the potential relationship between short sleep risks and cognitive function from the perspective of inflammatory biomarkers and cellular pathways: Insights from population-based and mice studies.

AIMS: The molecular mechanism of short-sleep conditions on cognition remains largely unknown. This research aimed to investigate associations between short sleep, inflammatory biomarkers and cognitive function in the US population (NHANES data 2011-2014) and explore cellular mechanisms in mice. METHODS: Systemic immune-inflammation index (SII) was calculated using blood-cell based biomarkers. Further, we employed integrated bioinformatics and single-cell transcriptomics (GSE137665) to examine how short sleep exposure influenced the molecular pathways associated with inflammation in the brain. To explore the signaling pathways and biological processes of sleep deprivation, we carried out enrichment analyses utilizing the GO and KEGG databases. RESULTS: Population results showed that, compared with normal sleep group, severe short sleep was associated with lower cognitive ability in all the four tests. Moreover, a higher SII level was correlated with lower scores of cognitive tests. In mice study, elevated activation of the inflammatory pathway was observed in cell subgroups of neurons within the sleep deprivation and recovery sleep cohorts. Additionally, heightened expression of oxidative stress and integrated stress response pathways was noted in GABAergic neurons during sleep deprivation. CONCLUSION: This study contributed to the understanding of the influence of short sleep on cognitive function and its cellular mechanisms.

Accelerometer-measured physical activity and sedentary behaviour are associated with C-reactive protein in US adults who get insufficient sleep: A threshold and isotemporal substitution effect analysis.

This study aimed to investigate the association between physical activity, sedentary behaviour and chronic inflammation in short sleep adults. The study included 2,113 NHANES participants with self-reported insufficient sleep. C-reactive protein (CRP) was used as the inflammatory biomarker. Physical activity and sedentary behaviour were objectively measured by accelerometers. Weighted regression model, two - piecewise linear regression model, and restricted cubic splines were applied to evaluate associations mentioned above. An isotemporal substitution model was used to assess the modelled effects of replacing sedentary time (ST) with moderate-to-vigorous levels of physical activity (MVPA) or light physical activity (LPA). After adjusting for potential confounding factors, higher levels of ST and lower levels of LPA or MVPA were associated with higher CRP levels. Isotemporal substitution analysis indicated that replacing 30 minutes of ST with 30 minutes of MVPA was associated with a significant decrease in CRP levels. Saturation analysis suggested that the association between MVPA and CRP may plateau at over 20 minutes of MVPA per day. Findings of this study provides insight into the potential benefits of replacing ST with MVPA. This study also suggests that increasing MVPA beyond a certain point may not provide additional anti-inflammatory benefits in a short sleep population.

The role of dietary intake of live microbes in the association between leisure-time physical activity and depressive symptoms: a population-based study.

Current research has shown promising associations between factors such as diet, total physical activity, and mental health outcomes, acknowledging the intricate interplay between these variables. However, the role of dietary intake of live microbes, coupled with leisure-time physical activity (LTPA), in their relationship to depressive symptoms necessitates further exploration. The present study examined a cohort of 25 747 individuals who participated in the National Health and Nutrition Examination Survey between the years 2007 and 2018. Patient's Health Questionnaire (PHQ-9) was employed, whereby individuals scoring ≥ 10 were classified as exhibiting symptoms of depression. LTPA status was reported by the Global Physical Activity Questionnaire and calculated by metabolic equivalent-minutes/week. Foods consumed by participants were evaluated by live microbes per gram, which were categorized into three groups: low, medium, and high. After controlling for all covariates, findings indicated that LTPA was negatively associated with depressive symptoms (OR (95% confidence interval (CI): 0.983 (0.976, 0.990), p < 0.001). Participating in more LTPA was positively correlated with consuming all three levels of dietary live microbes (low, ß (95% CI): 0.086 (0.063, 0.109); medium, ß (95% CI): 0.009 (0.007, 0.012); high, ß (95% CI): 0.002 (0.001, 0.002)). Moreover, taking more foods with medium live microbes was associated with lower depressive likelihood (OR (95% CI): 0.931(0.882, 0.982), p = 0.010). Intake of medium and high levels of live microbes mediated the association between LTPA and depressive symptoms by 4.15% and 0.83%, respectively. Dietary intake of foods containing medium and high levels of live microbes may be a mediator of LTPA's negative association with depressive symptoms.

Inverted U-shaped relationship between sleep duration and phenotypic age in US adults: a population-based study.

Sleep is a modifiable behavior that can be targeted in interventions aimed at promoting healthy aging. This study aims to (i) identify the sleep duration trend in US adults; (ii) investigate the relationship between sleep duration and phenotypic age; and (iii) explore the role of exercise in this relationship. Phenotypic age as a novel index was calculated according to biomarkers collected from US adults based on the National Health and Nutrition Examination Survey (NHANES). Sleep information was self-reported by participants and discerned through individual interviews. The principal analytical method employed was weighted multivariable linear regression modeling, which accommodated for the complex multi-stage sampling design. The potential non-linear relationship was explored using a restricted cubic spline (RCS) model. Furthermore, subgroup analyses evaluated the potential effects of sociodemographic and lifestyle factors on the primary study outcomes. A total of 13,569 participants were finally included in, thereby resulting in a weighted population of 78,880,615. An examination of the temporal trends in sleep duration revealed a declining proportion of individuals with insufficient and markedly deficient sleep time since the 2015-2016 cycle. Taken normal sleep group as a reference, participants with extreme short sleep [ß (95% CI) 0.582 (0.018, 1.146), p = 0.044] and long sleep [ß (95% CI) 0.694 (0.186, 1.203), p = 0.010] were both positively associated with phenotypic age using the fully adjusted model. According to the dose-response relationship between sleep duration and phenotypic age, long sleep duration can benefit from regular exercise activity, whereas short sleep duration with more exercise tended to have higher phenotypic age. There is an inverted U-shaped relationship between short and long sleep durations and phenotypic age. This study represents an important step forward in our understanding of the complex relationship between sleep and healthy aging. By shedding light on this topic and providing practical exercise recommendations for promoting healthy sleep habits, researchers can help individuals live longer, healthier, and more fulfilling lives.

Efficacy and Safety Assessment of Intrathoracic Perfusion Chemotherapy Combined with immunological factor Interleukin-2 in the Treatment of Advanced Non-Small Cell Lung Cancer: A Retrospective Cohort Study.

Objective: This study evaluated the efficacy and safety of the gemcitabine and oxaliplatin intrathoracic perfusion chemotherapy (IPCGOR) regimen combined with interleukin-2 (IL-2) for advanced non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of 460 advanced NSCLC patients from the Yunnan Province Early Cancer Diagnosis and Treatment Project (June 2020-October 2022), assessing the IPCGOR and IL-2 combination. Outcomes were measured based on RECIST 1.1 criteria, focusing on objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (MOS), and treatment safety. Results: The treatment demonstrated an ORR of 67.4%, a DCR of 97.4%, an mPFS of 8.5 months, and an MOS of 12.5 months. 14 patients underwent successful surgery post-treatment. Common adverse reactions were manageable, with no treatment-related deaths reported. Conclusion: The IPCGOR combined with IL-2 regimen shows promising efficacy and a tolerable safety profile for advanced NSCLC. These findings suggest its potential as a reference for treating advanced NSCLC. However, the study's retrospective nature and single-center design pose limitations. Future research should focus on prospective studies, randomized controlled trials, and long-term outcome assessments, particularly in diverse patient subgroups, to further validate and refine the clinical application of this regimen.

Relationship between accelerometer-measured sleep duration and Stroop performance: a functional near-infrared spectroscopy study among young adults.

Objectives: Short sleep is becoming more common in modern society. This study aimed to explore the relationship between accelerometer-measured sleep duration and cognitive performance among young adults as well as the underlying hemodynamic mechanisms. Methods: A total of 58 participants were included in this study. Participants were asked to wear an ActiGraph GT3X+ accelerometer to identify their sleep duration for 7 consecutive days. Cognitive function was assessed by the Stroop test. Two conditions, including the congruent and incongruent Stroop, were set. In addition, stratified analyses were used to examine sensitivity. 24-channel functional near-infrared spectroscopy (fNIRS) equipment was applied to measure hemodynamic changes of the prefrontal cortex (PFC) during cognitive tasks. Results: Results showed that sleep duration was positively associated with accuracy of the incongruent Stroop test (0.001 (0.000, 0.002), p = 0.042). Compared with the regular sleep (≥7 h) group, lower accuracy of the incongruent Stroop test (-0.012 (-0.023, -0.002), p = 0.024) was observed in the severe short sleep (<6 h). Moreover, a stratified analysis was conducted to examining gender, age, BMI, birthplace, and education's impact on sleep duration and the incongruent Stroop test accuracy, confirming a consistent correlation across all demographics. In the severe short sleep group, the activation of left middle frontal gyri and right dorsolateral superior frontal gyri were negatively associated with the cognitive performance. Conclusions: This study emphasized the importance of maintaining enough sleep schedules in young college students from a fNIRS perspective. The findings of this study could potentially be used to guide sleep time in young adults and help them make sleep schemes.

Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics.

Background: Aging is an important factor in the development of Alzheimer's disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD. Methods: The study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes. Results: A correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD. Conclusion: We explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation.

Mediation Role of Recreational Physical Activity in the Relationship between the Dietary Intake of Live Microbes and the Systemic Immune-Inflammation Index: A Real-World Cross-Sectional Study.

The main topic of this research is the relationship between dietary intake of live microbe-containing (LMC) foods, recreational physical activity (RPA), and the systemic immune-inflammation index (SII). This study presented a cohort of 26,254 individuals in the National Health and Nutrition Examination Survey (NHANES), representing an estimated weighted population of 193,637,615 in the United States. Weighted multivariable linear regression models were used in consideration of the multi-stage sampling design. Results: The study found that medium-LMC foods were negatively associated with the SII [ß (95% CI): -4.807 (-7.752, -1.862), p = 0.002], indicating that their intake was correlated with lower levels of the SII. However, no significant associations were found with low- or high-LMC foods. The study also explored the relationship between RPA and the SII, finding that more time spent in RPA was negatively associated with the SII [ß (95% CI): -0.022 (-0.034, -0.011), p < 0.001]. A mediation analysis was conducted to investigate the role of RPA in the relationship between medium-LMC food intake and the SII. The analysis revealed that RPA had a notable indirect effect, contributing to 6.7% of the overall change in the SII. Overall, this study suggests that medium-LMC food intake and RPA may have beneficial effects on systemic immune inflammation.

The role of education attainment on 24-hour movement behavior in emerging adults: evidence from a population-based study.

Purpose: The purpose of this study was to explore the relationship between education level and health behavior including sleep, work activity, exercise activity, and sedentary behavior among emerging adults. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2007 and 2018. The study sample included 4,484 emerging adults aged 18-25 years and the weighted participants were 30,057,813. Weighted multivariable regression analysis was performed to investigate the association between education level and the aforementioned health behavior, adjusting for age, gender, race/ethnicity, marital status, poverty-income ratio, BMI, smoking, and alcohol drinking status. Results: This study revealed that higher education level was associated with shorter sleep duration [Fully adjusted model, ß (95% CI): -0.588 (-0.929, -0.246), p < 0.001]. Additionally, those with higher education levels were more likely to allocate time in sedentary behavior [ß (95% CI): 90.162 (41.087, 139.238), p < 0.001]. Moreover, higher education level was related to less work activity [ß (95% CI): -806.991 (-1,500.280, -113.703), p = 0.023] and more exercise activity time [ß (95% CI): 118.196 (-21.992, 258.385), p = 0.097]. Subgroup analysis further verified this trend and detected that males with higher education level tended to participate in less work activity [ß (95% CI): -1,139.972 (-2,136.707, -143.237), p = 0.026] while females with higher education level tended to engage in more exercise activity [Fully adjusted model, ß (95% CI): 141.709 (45.468, 237.950), p = 0.004]. Conclusion: This study highlighted the importance of education level as a significant factor in promoting healthy behavior among emerging adults. The findings underscored the need for the Ministry of Education to prioritize educating this demographic about the significance of maintaining adequate sleep patterns and reducing sedentary habits. Encouraging them to allocate more time for work and physical activities can significantly contribute to their overall wellbeing and success, ultimately fostering a healthier next generation.

Mechanisms of action of the BCL-2 inhibitor venetoclax in multiple myeloma: a literature review.

Abnormal cellular apoptosis plays a pivotal role in the pathogenesis of Multiple Myeloma (MM). Over the years, BCL-2, a crucial anti-apoptotic protein, has garnered significant attention in MM therapeutic research. Venetoclax (VTC), a small-molecule targeted agent, effectively inhibits BCL-2, promoting the programmed death of cancerous cells. While VTC has been employed to treat various hematological malignancies, its particular efficacy in MM has showcased its potential for broader clinical applications. In this review, we delve into the intricacies of how VTC modulates apoptosis in MM cells by targeting BCL-2 and the overarching influence of the BCL-2 protein family in MM apoptosis regulation. Our findings highlight the nuanced interplay between VTC, BCL-2, and MM, offering insights that may pave the way for optimizing therapeutic strategies. Through this comprehensive analysis, we aim to lay a solid groundwork for future explorations into VTC's clinical applications and the profound effects of BCL-2 on cellular apoptosis.

A literature review: mechanisms of antitumor pharmacological action of leonurine alkaloid.

Leonurine refers to the desiccated aerial portion of a plant in the Labiatae family. The primary bioactive constituent of Leonurine is an alkaloid, Leonurine alkaloid (Leo), renowned for its substantial therapeutic efficacy in the treatment of gynecological disorders, in addition to its broad-spectrum antineoplastic capabilities. Over recent years, the pharmacodynamic mechanisms of Leo have garnered escalating scholarly interest. Leo exhibits its anticancer potential by means of an array of mechanisms, encompassing the inhibition of neoplastic cell proliferation, induction of both apoptosis and autophagy, and the containment of oncogenic cell invasion and migration. The key signal transduction pathways implicated in these processes include the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), the Phosphoinositide3-Kinase/Serine/Threonine Protein Kinase (PI3K/AKT), the Signal Transducer and Activator of Transcription 3 (STAT3), and the Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase (MAP/ERK). This paper commences with an exploration of the principal oncogenic cellular behaviors influenced by Leo and the associated signal transduction pathways, thereby scrutinizing the mechanisms of Leo in the antineoplastic sequence of events. The intention is to offer theoretical reinforcement for the elucidation of more profound mechanisms underpinning Leo's anticancer potential and correlating pharmaceutical development.

Systematic and meta-based evaluation of the relationship between the built environment and physical activity behaviors among older adults.

Objectives: Existing assertions about the relationship between various factors of the built environment and physical activity behaviors are inconsistent and warrant further exploration and analysis. Methods: This study systematically searched PubMed, Embase, Web of Science, Scopus, the Cochrane Library and Google Scholar for the effect of the built environment on the physical activity behaviors of older adults. R software was used to calculate the meta-estimated odds ratio with a 95% confidence interval. Simultaneously, the quality of included studies was evaluated using an observational study quality evaluation standard recommended by American health care quality and research institutions. Results: A total of 16 original researches were included in this meta-analysis and eight factors of the built environment were evaluated. These factors which ranked from high to low according to their impact were traffic safety (OR = 1.58, 95% CI [1.14-2.20]), destination accessibility (OR = 1.24, 95% CI [1.06-1.44]), aesthetics of sports venues (OR = 1.21, 95% CI [1.07-1.37]), virescence of sports venues (OR = 1.14, 95% CI [1.06-1.23]), building density (OR = 1.07, 95% CI [1.02-1.13]). Additionally, it seemed that there was no potential association between mixed land use (OR = 1.01, 95% CI [0.92-1.10]), the quality of pedestrian facilities (OR = 1.00, 95% CI [0.92-1.08]) or commercial facilities (OR = 0.94, 95% CI [0.88-1.00]) and physical activity behaviors of older adults. Conclusions: The built environment has been found to exhibit a significant relationship with the physical activity behaviors of older adults. It is proposed that factors such as traffic safety, destination accessibility, aesthetics of sports venues, virescence of sports venues, and building density be given more consideration when aiming to promote physical activity levels among older adults.

Accelerometer-measured physical activity patterns are associated with phenotypic age: Isotemporal substitution effects.

Prolonged sitting appears to accelerate aging, while optimal physical activity patterns have been found to delay the process. It is an emerging topic, and no conclusions have been reached regarding the relationship between physical activity patterns and biomarkers-measured aging. Hence, the aim of this study was to investigate the association between sensor-based objectively measured physical activity and phenotypic age using a nationwide population from the National Health and Nutrition Examination Survey (NHANES) in the United States. Weighted linear regression models were performed to evaluate the association between sedentary behavior, light-intensity physical activity (LPA), moderate-to-vigorous physical activity (MVPA) and phenotypic age. A total of 6439 eligible participants were included and the weighted respondents were 49,964,300. Results showed that prolonged sitting was positively associated with phenotypic age in the fully adjusted model [ß (95% CI): 0.009(0.007,0.011), p < 0.001], while increasing volume of LPA and MVPA was associated with younger phenotypic age using the fully adjusted model [ß (95% CI): -0.010(-0.013,-0.006), p < 0.001; -0.062(-0.075,-0.048), p < 0.001]. By utilizing the Isotemporal Substitution Model, it was found that replacing 30 min of sedentary behavior with 30 min of LPA or MVPA per day was associated with estimated 0.4 or 1.9 years of phenotypic age reduction. According to the study's findings, maintaining a certain level of physical activity could delay the process of aging and intensity matters.

The impact of concurrent bacterial lung infection on immunotherapy in patients with non-small cell lung cancer: a retrospective cohort study.

Objective: To find out how bacterial lung infections (BLI) affect the effectiveness of therapy and the rate of pneumonia caused by pneumonia related to checkpoint inhibitors (CIP) in patients with non-small cell lung cancer (NSCLC) who are getting immunotherapy with checkpoint inhibitors (ICIs). Patients and methods: 507 NSCLC patients who received at least two ICI treatments between June 2020 and December 2022 at the Affiliated Hospital of Kunming University of Science and Technology(AHKUST) were included in a retrospective cohort study. Based on whether there was a concurrent BLI diagnosis from high-resolution CT scans of the chest, the patients were divided into two groups: 238 in the NSCLC with BLI group (NSCLC-BLI group), and 269 in the NSCLC alone group. The collected therapeutic outcome measures included the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence rate of CIP. We analyzed the effect of BLI on the therapeutic efficacy of ICI treatment and the incidence rate of CIP in NSCLC patients.Inclusion criteria based on NSCLC patients staged I to IV according to the 8th edition of the International Association for Lung Cancer Research (IASLC). Results: The NSCLC-BLI group showed superior ORR to the NSCLC group when treated with ICIs. Multifactorial logistic regression and Cox analyses, adjusted for confounders, identified BLI as an independent positive prognostic factor for ORR (HR=0.482, 95%CI: 0.391-0.550; P<0.001) and PFS (HR=0.619; 95%CI: 0.551-0.771; P<0.001). No correlation between BLI and OS was found. Out of 26 cases of CIP, 12 were in the NSCLC-BLI group and 14 in the NSCLC group, with no significant difference in incidence (P=0.145). Conclusion: NSCLC patients with BLI receiving ICI treatment show superior ORR and PFS compared to NSCLC alone without an increased CIP risk, positioning BLI as a predictive factor for improved outcomes in NSCLC patients receiving ICIs. However, the study has limitations including its retrospective nature and lacking data on BLI bacteria types and levels, which could influence therapy outcomes.