Identification of Blood Biomarkers Related to Energy Metabolism and Construction of Diagnostic Prediction Model Based on Three Independent Alzheimer's Disease Cohorts.

Background: Blood biomarkers are crucial for the diagnosis and therapy of Alzheimer's disease (AD). Energy metabolism disturbances are closely related to AD. However, research on blood biomarkers related to energy metabolism is still insufficient. Objective: This study aims to explore the diagnostic and therapeutic significance of energy metabolism-related genes in AD. Methods: AD cohorts were obtained from GEO database and single center. Machine learning algorithms were used to identify key genes. GSEA was used for functional analysis. Six algorithms were utilized to establish and evaluate diagnostic models. Key gene-related drugs were screened through network pharmacology. Results: We identified 4 energy metabolism genes, NDUFA1, MECOM, RPL26, and RPS27. These genes have been confirmed to be closely related to multiple energy metabolic pathways and different types of T cell immune infiltration. Additionally, the transcription factors INSM2 and 4 lncRNAs were involved in regulating 4 genes. Further analysis showed that all biomarkers were downregulated in the AD cohorts and not affected by aging and gender. More importantly, we constructed a diagnostic prediction model of 4 biomarkers, which has been validated by various algorithms for its diagnostic performance. Furthermore, we found that valproic acid mainly interacted with these biomarkers through hydrogen bonding, salt bonding, and hydrophobic interaction. Conclusions: We constructed a predictive model based on 4 energy metabolism genes, which may be helpful for the diagnosis of AD. The 4 validated genes could serve as promising blood biomarkers for AD. Their interaction with valproic acid may play a crucial role in the therapy of AD.

Prevalence, cessation, and geographical variation of smoking among middle-aged and elderly adults in China: A population-based study.

INTRODUCTION: Smoking significantly burdens human health, contributing to an increasing incidence of mortality and morbidity. This study aims to explore the prevalence of smoking, cessation, and the association between various risk factors and smoking intensity measured in pack-years among Chinese adults. METHODS: During 2020-2021, the China Stroke High-risk Population Screening and Intervention Program (CSHPSIP) invited participants aged ≥40 years from 31 provinces in mainland China. This cross-sectional study presents the standardized prevalence of smoking and cessation across various demographics, including age, sex, residence, income, education level, BMI, and geographical region of residence. Multivariable logistic regression was used to examine the associations between smoking pack-years and related factors. RESULTS: Among 524741 participants (mean age: 61.9 ± 10.9 years; 41.1% male; 58.9% female), standardized smoking prevalence was 19.3% (95% CI: 19.2-19.4), with men (37.2%; 95% CI: 37.0-37.4) displaying significantly higher rates than women (1.3%; 95% CI: 1.2-1.3). Smoking cessation rate stood at 11.2% (95% CI: 11.0-11.4), with 11.3% (95% CI: 11.1-11.5) for men and 8.4% (95% CI: 7.5-9.2) for women. Urban residents and those with advanced education had lower smoking rates and higher cessation rates. Additionally, the dose-response relationship indicated a more pronounced association between higher smoking pack-years and elevated health risks, including hypertension (AOR=1.30; 95% CI: 1.24-1.36), diabetes (AOR=1.26; 95% CI: 1.20-1.33), hyperlipidemia (AOR=1.22; 95% CI: 1.16-1.28), heart disease (AOR=1.40; 95% CI: 1.26-1.54), and stroke (AOR=1.23; 95% CI: 1.10-1.36). CONCLUSIONS: This comprehensive study emphasizes the profound impact of smoking on health in Chinese adults, indicating the critical need for tailored cessation programs, particularly for middle-aged individuals, men, rural residents, and those with lower level of education.

Selective Adsorption of Hazardous Substances from Wastewater by Hierarchical Oxide Composites: A Review.

Large volumes of wastewater containing toxic contaminants (e.g., heavy metal ions, organic dyes, etc.) are produced from industrial processes including electroplating, mining, petroleum exploitation, metal smelting, etc., and proper treatment prior to their discharge is mandatory in order to alleviate the impacts on aquatic ecosystems. Adsorption is one of the most effective and practical methods for removing toxic substances from wastewater due to its simplicity, flexibility, and economics. Recently, hierarchical oxide composites with diverse morphologies at the micro/nanometer scale, and the combination advantages of oxides and composite components have been received wide concern in the field of adsorption due to their multi-level structures, easy functionalization characteristic resulting in their large transport passages, high surface areas, full exposure of active sites, and good stability. This review summarizes the recent progress on their typical preparation methods, mainly including the hydrothermal/solvothermal method, coprecipitation method, template method, polymerization method, etc., in the field of selective adsorption and competitive adsorption of hazardous substances from wastewater. Their formation processes and different selective adsorption mechanisms, mainly including molecular/ion imprinting technology, surface charge effect, hard-soft acid-base theory, synergistic effect, and special functionalization, were critically reviewed. The key to hierarchical oxide composites research in the future is the development of facile, repeatable, efficient, and scale preparation methods and their dynamic adsorption with excellent cyclic regeneration adsorption performance instead of static adsorption for actual wastewater. This review is beneficial to broaden a new horizon for rational design and preparation of hierarchical oxide materials with selective adsorption of hazardous substances for wastewater treatment.

Brain-computer interface digital prescription for neurological disorders.

Neurological and psychiatric diseases can lead to motor, language, emotional disorder, and cognitive, hearing or visual impairment By decoding the intention of the brain in real time, the Brain-computer interface (BCI) can first assist in the diagnosis of diseases, and can also compensate for its damaged function by directly interacting with the environment; In addition, provide output signals in various forms, such as actual motion, tactile or visual feedback, to assist in rehabilitation training; Further intervention in brain disorders is achieved by close-looped neural modulation. In this article, we envision the future BCI digital prescription system for patients with different functional disorders and discuss the key contents in the prescription the brain signals, coding and decoding protocols and interaction paradigms, and assistive technology. Then, we discuss the details that need to be specially included in the digital prescription for different intervention technologies. The third part summarizes previous examples of intervention, focusing on how to select appropriate interaction paradigms for patients with different functional impairments. For the last part, we discussed the indicators and influencing factors in evaluating the therapeutic effect of BCI as intervention.

Astrocyte-derived Interleukin-31 causes poor prognosis in elderly patients with intracerebral hemorrhage.

The incidence of intracerebral hemorrhage (ICH) is increasing every year, with very high rates of mortality and disability. The prognosis of elderly ICH patients is extremely unfavorable. Interleukin, as an important participant in building the inflammatory microenvironment of the central nervous system after ICH, has long been the focus of neuroimmunology research. However, there are no studies on the role IL31 play in the pathologic process of ICH. We collected para-lesion tissue for immunofluorescence and flow cytometry from the elderly and young ICH patients who underwent surgery. Here, we found that IL31 expression in the lesion of elderly ICH patients was significantly higher than that of young patients. The activation of astrocytes after ICH releases a large amount of IL31, which binds to microglia through IL31R, causing a large number of microglia to converge to the hematoma area, leading to the spread of neuroinflammation, apoptosis of neurons, and ultimately resulting in poorer recovery of nerve function. Interfering with IL31 expression suppresses neuroinflammation and promotes the recovery of neurological function. Our study demonstrated that elderly patients release more IL31 after ICH than young patients. IL31 promotes the progression of neuroinflammation, leading to neuronal apoptosis as well as neurological decline. Suppression of high IL31 concentrations in the brain after ICH may be a promising therapeutic strategy for ICH.

Geographic and ethnicity variation in the prevalence of middle-aged and elderly adult obesity in China in 2020.

AIM: The objective of this study is to evaluate the mean body mass index (BMI), general obesity and abdominal obesity in adults aged ≥40 years residing in China in 2020, and to analyse variations in these factors across different geographic areas and subpopulations. METHODS: We utilized data from the National Stroke High-Risk Population Screening programme to calculate and compare the mean BMI and prevalence of obesity across various demographics, including sex, age, urban-rural locality, geographical region (province) and ethnicity status. RESULTS: In our study, we found that the standardized mean BMI level was 24.65 kg/m2 [95% confidence interval (CI): 24.50-22.84] in men and 24.31 kg/m2 (95% CI: 24.15-24.45) in women. Using the criteria from China, we found that the standardized prevalence of general obesity and abdominal obesity was 13.13% (95% CI: 13.05-13.21%) and 33.03% (95 CI: 32.92-33.14%), respectively. Our study also identified significant effects of age, sex, urban-rural locality, province and ethnicity status on the prevalence of obesity. Overall, our study estimated that in 2020, approximately 91.1 million adults aged ≥40 years in China were obese (46.5 million men and 44.6 million women), while 229.2 million adults (110.4 million men and 118.8 million women) were diagnosed with abdominal obesity. CONCLUSION: Our research has revealed compelling new evidence about the obesity epidemic among Chinese adults aged ≥40 years, particularly at the provincial and ethnic levels. As a result, more targeted and effective prevention strategies should be developed to alleviate the burden of obesity.

China Trends in Physical Inactivity from 2013 to 2019: An Analysis of 4.23 Million Participants.

INTRODUCTION: This study aimed to evaluate recent trends in physical inactivity prevalence by sociodemographic characteristics and the province of China's residence between 2013 and 2019. METHODS: The study included 4,229,616 participants 40 yr or older from 414 geographically defined localities in China during the 7-yr period. Self-reported total physical inactivity was collected to determine the standardized prevalence of physical inactivity. Logistic regression analysis was used to examine the association between physical inactivity and stroke risk, obtaining odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Results showed that the standardized prevalence of physical inactivity increased from 22.12% (95% CI = 21.99%-22.45%) in 2013 to 28.79% (95% CI = 28.48%-29.19%) in 2019, with an absolute difference of 6.67% (95% CI = 6.15% to 7.16%) and a yearly increase rate of 5.03% (95% CI = 4.85% to 5.21%). In 2019, physical inactivity was higher in female and rural participants (female = 29.55%, rural = 29.46%) than in male and urban participants (male = 28.03%, urban = 28.26%). The prevalence of physical inactivity also varied by race/ethnic groups, with the highest prevalence observed among Uyghur (47.21%) and the lowest among Yizu (14.84%). Additionally, the prevalence of physical inactivity differed by province, ranging from 14.44% in Beijing to 50.09% in Tianjin in 2019. Multivariate analyses showed that physical inactivity was associated with a higher risk of stroke (OR = 1.17, 95% CI = 1.12-1.21, P < 0.001). CONCLUSIONS: In conclusion, our study found an overall increase in physical inactivity prevalence among Chinese adults ≥40 yr old from 2013 to 2019, with significant variation across regions, sex, ages, and race/ethnic groups.

China stroke surveillance report 2021.

Since 2015, stroke has become the leading cause of death and disability in China, posing a significant threat to the health of its citizens as a major chronic non-communicable disease. According to the China Stroke High-risk Population Screening and Intervention Program, an estimated 17.8 million [95% confidence interval (CI) 17.6-18.0 million] adults in China had experienced a stroke in 2020, with 3.4 million (95% CI 3.3-3.5 million) experiencing their first-ever stroke and another 2.3 million (95% CI 2.2-2.4 million) dying as a result. Additionally, approximately 12.5% (95% CI 12.4-12.5%) of stroke survivors were left disabled, as defined by a modified Rankin Scale score greater than 1, equating to 2.2 million (95% CI 2.1-2.2 million) stroke-related disabilities in 2020. As the population ages and the prevalence of risk factors like diabetes, hypertension, and hyperlipidemia continues to rise and remains poorly controlled, the burden of stroke in China is also increasing. A large national epidemiological survey initiated by the China Hypertension League in 2017 showed that the prevalence of hypertension was 24.7%; the awareness, treatment, and control rates in hypertensive patients were: 60.1%, 42.5%, and 25.4%, respectively. A nationally representative sample of the Chinese mainland population showed that the weighted prevalence of total diabetes diagnosed by the American Diabetes Association criteria was 12.8%, suggesting there are 120 million adults with diabetes in China, and the awareness, treatment, and control rates in diabetic patients were: 43.3%, 49.0%, and 49.4%, respectively. The "Sixth National Health Service Statistical Survey Report in 2018" showed that the proportion of the obese population in China was 37.4%, an increase of 7.2 points from 2013. Data from 1599 hospitals in the Hospital Quality Monitoring System and Bigdata Observatory Platform for Stroke of China (BOSC) showed that a total of 3,418,432 stroke cases [mean age ± standard error (SE) was (65.700 ± 0.006) years, and 59.1% were male] were admitted during 2020. Of those, over 80% (81.9%) were ischemic stroke (IS), 14.9% were intracerebral hemorrhage (ICH) strokes, and 3.1% were subarachnoid hemorrhage (SAH) strokes. The mean ± SE of hospitalization expenditures was Chinese Yuan (CNY) (16,975.6 ± 16.3), ranging from (13,310.1 ± 12.8) in IS to (81,369.8 ± 260.7) in SAH, and out-of-pocket expenses were (5788.9 ± 8.6), ranging from (4449.0 ± 6.6) in IS to (30,778.2 ± 156.8) in SAH. It was estimated that the medical cost of hospitalization for stroke in 2020 was CNY 58.0 billion, of which the patient pays approximately CNY 19.8 billion. In-hospital death/discharge against medical advice rate was 9.2% (95% CI 9.2-9.2%), ranging from 6.4% (95% CI 6.4-6.5%) for IS to 21.8% for ICH (95% CI 21.8-21.9%). From 2019 to 2020, the information about 188,648 patients with acute IS receiving intravenous thrombolytic therapy (IVT), 49,845 patients receiving mechanical thrombectomy (MT), and 14,087 patients receiving bridging (IVT + MT) were collected through BOSC. The incidence of intracranial hemorrhage during treatment was 3.2% (95% CI 3.2-3.3%), 7.7% (95% CI 7.5-8.0%), and 12.9% (95% CI 12.3-13.4%), respectively. And in-hospital death/discharge against medical advice rate was 8.9% (95% CI 8.8-9.0%), 16.5% (95% CI 16.2-16.9%), and 16.8% (95% CI 16.2-17.4%), respectively. A prospective nationwide hospital-based study was conducted at 231 stroke base hospitals (Level III) from 31 provinces in China through BOSC from January 2019 to December 2020 and 136,282 stroke patients were included and finished 12-month follow-up. Of those, over 86.9% were IS, 10.8% were ICH strokes, and 2.3% were SAH strokes. The disability rate [% (95% CI)] in survivors of stroke at 3-month and 12-month was 14.8% (95% CI 14.6-15.0%) and 14.0% (95% CI 13.8-14.2%), respectively. The mortality rate [% (95% CI)] of stroke at 3-month and 12-month was 4.2% (95% CI 4.1-4.3%) and 8.5% (95% CI 8.4-8.6%), respectively. The recurrence rate [% (95% CI)] of stroke at 3-month and 12-month was 3.6% (95% CI 3.5-3.7%) and 5.6% (95% CI 5.4-5.7%), respectively. The Healthy China 2030 Stroke Action Plan was launched as part of this review, and the above data provide valuable guidelines for future stroke prevention and treatment efforts in China.

Impacts of exposure to ambient temperature and altitude on the burden of stroke.

OBJECTIVE: To evaluate the impact of ambient temperature and altitude exposure on the burden of stroke in a Chinese cohort. METHODS: This study was conducted using data from the National Stroke High-Risk Population Screening System 2020, which assess the overall prevalence, incidence, and mortality rate of stroke in China. For this study, we obtained the annual mean ambient temperature, diurnal temperature range, and altitude for each city. Body mass index (BMI) of participants were calculated. RESULT: The sample comprised 676,394 adults aged 40 years or older from 170 cities in 31 provinces in China. A negative linear relationship between mean ambient temperature and stroke risk (incidence and prevalence) as well as a negative association between mean ambient temperature and stroke mortality had been found. A nonlinear relationship with decreased risk in both high and low diurnal temperature range is observed for stroke burden (incidence, prevalence, and mortality). There is no significant correlation between city altitude and stroke burden. The U-shaped relationships of BMI with the incidence and prevalence of stroke indicate that the lowest incidence and prevalence are observed when BMI is approximately 20. CONCLUSION: Overall, our study provides important insights into the environmental and individual factors that contribute to the burden of stroke in China, and may inform public health interventions aimed at reducing this burden.

Low Ca diet leads to increased Ca retention by changing the gut flora and ileal pH value in laying hens.

Osteoporosis is a common degenerative metabolic bone disease in caged laying hens. Intensive egg production mobilizing large amounts of Ca from bone for eggshell formation, consequently leading to Ca deficiency, has been recognized as a critical factor causing osteoporosis in commercial laying hens. The aim of this study was to examine the effect of Ca deficiency on the function of the gut microbiota-bone axis and related egg production traits and bone health in laying hens. Twenty-four 48-week-old laying hens were fed a control diet (Control, 3.72%) or a low Ca diet (LC, 2.04%) for 60 d (n = 12). Compared to the Control hens, the LC hens had higher levels of alkaline phosphatase and tartrate resistant acid phosphatase (P < 0.05) with lower bone strength, eggshell thickness, and eggshell strength (P < 0.05). In addition, the LC hens had higher plasma estradiol concentrations, while having lower concentrations of interleukin-1 (IL-1) and IL-6. The LC hens also had a lower pH value in the ileum with an increased Ca retention. The principal co-ordinates analysis showed significantly separate cecal microbiota populations between the Control and LC hens. The Prevotellaceae_UCG-001, Subdoligranulum, Peptococcus, and Eubacterium_hallii_group (P < 0.05) were higher, while the CHKC1001 and Sutterella (P < 0.05) were lower at the genus level in the LC hens. In addition, Prevotellaceae_UCG-001, Subdoligranulum and Eubacterium_hallii_group had a negative correlation, while Sutterella was positively correlated with ileal pH values. The transcriptome analysis revealed that the low Ca diet caused 20 and 31 genes to be significantly up- and down-regulated, respectively. The gene expressions of cystic fibrosis transmembrane conductance regulator, solute carrier family 26 member 3 of the anion exchangers, and mitogen-activated protein kinase 12 of pro-inflammatory factors were lower in the LC birds, which was correlated with the lower ileal pH values. These results suggest that the hens with low Ca diet-induced osteoporosis have an increased intestinal Ca retention with a decreased ileal pH value, correlated with the changes in Prevotellaceae_UCG-001, Subdoligranulum, and Eubacterium_hallii_group of beneficial genera. The results provide insights for further understanding and preventing osteoporosis in laying hens.

Osteocalcin and Its Potential Functions for Preventing Fatty Liver Hemorrhagic Syndrome in Poultry.

Osteocalcin (OCN) is synthesized and secreted by differentiating osteoblasts. In addition to its role in bone, OCN acts as a hormone in the pancreas, liver, muscle, fat, and other organs to regulate multiple pathophysiological processes including glucose homeostasis and adipic acid metabolism. Fat metabolic disorder, such as excessive fat buildup, is related to non-alcoholic fatty liver disease (NAFLD) in humans. Similarly, fatty liver hemorrhage syndrome (FLHS) is a metabolic disease in laying hens, resulting from lipid accumulation in hepatocytes. FLHS affects hen health with significant impact on poultry egg production. Many studies have proposed that OCN has protective function in mammalian NAFLD, but its function in chicken FLHS and related mechanism have not been completely clarified. Recently, we have revealed that OCN prevents laying hens from FLHS through regulating the JNK pathway, and some pathways related to the disease progression have been identified through both in vivo and vitro investigations. In this view, we discussed the current findings for predicting the strategy for using OCN to prevent or reduce FLHS impact on poultry production.

Intravenous Thrombolysis or Medical Management for Minor Strokes.

OBJECTIVE: To evaluate the outcomes of acute ischemic stroke patients with minor deficits treated with either intravenous thrombolysis (IVT) or routine medical management (MM). METHODS: The study included patients with acute ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) scores of 5 or less who were treated with IVT within 4.5 hours from symptom onset and were classified as the IVT group. The MM group consisted of an equal number of patients with minor strokes, matched for sex, age, and severity, who did not receive thrombolysis. Data on patient information were collected for both groups. RESULTS: A total of 26,236 patients were included in this study (13,208 in IVT and 13,208 in MM). Of these patients, 67.9% were men, and the mean age was 67.1 years (standard deviation: 10.9). At 3 months, the IVT group had a higher rate of stroke-independent outcome (Rankin Scale score of 0-2) compared with the MM group (IVT vs. MM: 91.6 vs. 88.6%, absolute difference: 2.5%, 95% confidence interval [CI]: 1.6-3.4%, p = 0.008; adjusted hazard ratio [HR]: 1.2, 95% CI: 1.1-1.4, p = 0.003). Furthermore, there was no significant difference in 3-month mortality rates between the IVT and MM groups (IVT vs. MM: 2.1 vs. 2.5%, absolute difference: -0.6%, 95% CI: -1.1 to 0.3%, p = 0.11; adjusted HR: 0.9, 95% CI: 0.8-1.2, p = 0.09). CONCLUSION: Compared with MM, IVT does not reduce mortality in minor ischemic stroke but improves functional outcomes in minor stroke with an NIHSS score of 3 to 5.

Estimated Burden of Stroke in China in 2020.

Importance: Stroke is the leading cause of death in China. However, recent data about the up-to-date stroke burden in China are limited. Objective: To investigate the urban-rural disparity of stroke burden in the Chinese adult population, including prevalence, incidence, and mortality rate, and disparities between urban and rural populations. Design, Setting, and Participants: This cross-sectional study was based on a nationally representative survey that included 676 394 participants aged 40 years and older. It was conducted from July 2020 to December 2020 in 31 provinces in mainland China. Main Outcomes and Measures: Primary outcome was self-reported stroke verified by trained neurologists during a face-to-face interviews using a standardized protocol. Stroke incidence were assessed by defining first-ever strokes that occurred during 1 year preceding the survey. Strokes causing death that occurred during the 1 year preceding the survey were considered as death cases. Results: The study included 676 394 Chinese adults (395 122 [58.4%] females; mean [SD] age, 59.7 [11.0] years). In 2020, the weighted prevalence, incidence, and mortality rates of stroke in China were 2.6% (95% CI, 2.6%-2.6%), 505.2 (95% CI, 488.5-522.0) per 100 000 person-years, and 343.4 (95% CI, 329.6-357.2) per 100 000 person-years, respectively. It was estimated that among the Chinese population aged 40 years and older in 2020, there were 3.4 (95% CI, 3.3-3.6) million incident cases of stroke, 17.8 (95% CI, 17.5-18.0) million prevalent cases of stroke, and 2.3 (95% CI, 2.2-2.4) million deaths from stroke. Ischemic stroke constituted 15.5 (95% CI, 15.2-15.6) million (86.8%) of all incident strokes in 2020, while intracerebral hemorrhage constituted 2.1 (95% CI, 2.1-2.1) million (11.9%) and subarachnoid hemorrhage constituted 0.2 (95% CI, 0.2-0.2) million (1.3%). The prevalence of stroke was higher in urban than in rural areas (2.7% [95% CI, 2.6%-2.7%] vs 2.5% [95% CI, 2.5%-2.6%]; P = .02), but the incidence rate (485.5 [95% CI, 462.8-508.3] vs 520.8 [95% CI, 496.3-545.2] per 100 000 person-years; P < .001) and mortality rate (309.9 [95% CI, 291.7-328.1] vs 369.7 [95% CI, 349.1-390.3] per 100 000 person-years; P < .001) were lower in urban areas than in rural areas. In 2020, the leading risk factor for stroke was hypertension (OR, 3.20 [95% CI, 3.09-3.32]). Conclusions and Relevance: In a large, nationally representative sample of adults aged 40 years or older, the estimated prevalence, incidence, and mortality rate of stroke in China in 2020 were 2.6%, 505.2 per 100 000 person-years, and 343.4 per 100 000 person-years, respectively, indicating the need for an improved stroke prevention strategy in the general Chinese population.