Intermolecular Formal [2π + 2σ] Cycloaddition of Enol Silyl Ethers with Bicyclo[1.1.0]butanes Promoted by Lewis Acids.

Silyl enol ethers react with bicyclo[1.1.0]butanes (BCBs) through Yb(OTf)3-promoted formal [2π + 2σ] cycloaddition reactions to furnish bicyclo[2.1.1]hexanes (BCHs). This new reaction tolerated a wide range of enol silyl ethers and BCBs. Furthermore, the amplification experiments and synthetic transformations of the cycloaddition compounds further highlighted their practicality.

Luminescence Probes in Bio-Applications: From Principle to Practice.

Bioanalysis based on optical imaging has gained significant progress in the last few decades. Luminescence probes are capable of detecting, monitoring, and tracing particular biomolecules in complex biological systems to figure out the roles of these molecules in organisms. Considering the rapid development of luminescence probes for bio-applications and their promising future, we have attempted to explore the working principles and recent advances in bio-applications of luminescence probes, in the hope of helping readers gain a detailed understanding of luminescence probes developed in recent years. In this review, we first focus on the current widely used luminescence probes, including fluorescence probes, bioluminescence probes, chemiluminescence probes, afterglow probes, photoacoustic probes, and Cerenkov luminescence probes. The working principles for each type of luminescence probe are concisely described and the bio-application of the luminescence probes is summarized by category, including metal ions detection, secretion detection, imaging, and therapy.

Ambient PM2.5 components might exacerbate bone loss among middle-aged and elderly women: evidence from a population-based cross-sectional study.

BACKGROUND: Previous studies have primarily focused on the links between fine particulate matter (PM2.5) and bone health among the general population instead of PM2.5 components and the specific population. We aimed to investigate the associations between PM2.5 components and bone health among middle-aged and elderly women. METHODS: A total of 748 middle-aged and elderly women were randomly sampled from 32 streets/villages in Hubei Province. The concentrations of ambient PM2.5 and its components were extracted across various residential areas from the Tracking Air Pollution in China (TAP) dataset. Bone mineral density measurements were obtained from dual-energy X-ray absorptiometry scans of study participants. Multivariable logistic and linear models were employed to assess the relationship between PM2.5 and its components and bone loss. RESULTS: Per interquartile range (IQR) increase in nitrate (NO3-) and ammonium (NH4+) concentrations were associated with 1.65 [95% confidence intervals (CI): 1.13, 2.30] and 1.77 (95% CI: 1.26, 2.49) times higher odds of osteoporosis, respectively. Long-term exposure to sulfate (SO42-), NO3-, and NH4+ was negatively associated with T-scores and bone mineral density in L1-L4 lumbar vertebrae. In addition, the elderly, women who have experienced menarche after the age of 14, and postmenopausal women were more susceptible to the water-soluble inorganic salts of PM2.5. CONCLUSION: The study emphasizes the need for comprehensive policies addressing air quality, with a specific focus on vulnerable populations such as middle-aged and elderly women. Public health interventions aimed at reducing ambient PM2.5 concentrations and minimizing exposure to its harmful components are crucial in mitigating the adverse impact on skeletal health and improving the overall well-being of communities.

Circ_0008571 modulates the phenotype of vascular smooth muscle cells by targeting miR-145-5p in intracranial aneurysms.

BACKGROUND: The dysfunction of human vascular smooth cells (hVSMCs) is significantly connected to the development of intracranial aneurysms (IAs). By suppressing the activity of microRNAs (miRNAs), circular RNAs (circRNAs) participate in IA pathogenesis. Nevertheless, the role of hsa_circ_0008571 in IAs remains unclear. METHODS: circRNA sequencing was used to identify circRNAs from human IA tissues. To determine the function of circ_0008571, Transwell, wound healing, and cell proliferation assays were conducted. To identify the target of circ_0008571, the analyses of CircInteractome and TargetScan, as well as the luciferase assay were carried out. Furthermore, circ_0008571 knockdown and over-expression were performed to investigate its functions in IA development and the underlying molecular mechanisms. RESULTS: Both hsa_circ_0008571 and Integrin beta 8 (ITGB8) were downregulated, while miR-145-5p transcription was elevated in the aneurysm wall of IAs patients compared to superficial temporal artery tissues. In vitro, cell migration and growth were dramatically suppressed after hsa_circ_0008571 overexpression. Mechanistically, has_circ_0008571 could suppress miR-145-5p activity by direct sponging. Moreover, we found that ITGB8 expression and the activation of the TGF-ß-mediated signaling pathway were significantly enhanced. CONCLUSION: The hsa_circ_0008571-miR-145-5p-ITGB8 axis plays an essential role in IA progression.

Association between long-term exposure to fine particulate matter and its chemical constituents and premature death in individuals living with HIV/AIDS.

Long-term exposure to fine particulate matter (PM2.5) is associated with an increased total mortality. However, the association of PM2.5 with mortality in people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS, PLWHA) and the relationship between its constituents and adverse outcomes remain unknown. In this cohort study, 28,140 PLWHA were recruited from the HIV/AIDS Comprehensive Response Information Management System of the Hubei Provincial Centre for Disease Control and Prevention in China between 2001 and 2020. The annual PM2.5 chemical composition data, including sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), black carbon (BC), and organic matter (OM), was extracted from the Tracking Air Pollution (TAP) dataset in China. A Cox proportional hazard model with time-varying exposure and time-to-event quantile-based generalized (g) computation was used to assess the associations between PM2.5 chemical constituents, and mortality in PLWHA. A multivariate Cox proportional hazard model estimated an excess hazard ratio (eHR) of 0.32% [95% confidence interval (CI): (0.01%, 0.64%)] for AIDS-related death (ARD), associated with 1 µg/m3 rise in PM2.5 exposure. An increase of 1 µg/m3 in NH4+ was associated with 5.13% [95% CI: (2.89%, 7.43%)] and 2.97% [95% CI: (1.52%, 4.44%)] increase in the risk of ARD and all-cause deaths (ACD), respectively. When estimated using survival-based quantile g-computation, the eHR for ARD with a joint change in a decile increase in all five components was 6.10% [95% CI: 3.77%, 8.48%)]. Long-term exposure to PM2.5 chemical composition, particularly NH4+ increased the risk of death in PLWHA. This study provides epidemiological evidence that SO42- and NH4+ increased the risk of ARD and that NH4+ increased the risk of ACD in PLWHA. Multi-constituent analyses further suggested that NH4+ may be a key component in increasing the risk of premature death in patients with HIV/AIDS. Individuals aged ≥65 with HIV/AIDS are more vulnerable to SO42-, and consequent ACD.

Cnicus benedictus extract-loaded electrospun gelatin wound dressing for treating diabetic wounds: An in vitro and in vivo study.

In the current study, Cnicus benedictus extract was loaded into electrospun gelatin scaffolds for diabetic wound healing applications. Scaffolds were characterized in vitro by mechanical testing, cell culture assays, electron microscopy, cell migration assay, and antibacterial assay. In vivo wound healing study was performed in a rat model of diabetic wound. In vitro studies revealed fibrous architecture of our developed dressings and their anti-inflammatory properties. In addition, Cnicus benedictus extract-loaded wound dressings prevented bacterial penetration. In vivo study showed that wound size reduction, collagen deposition, and epithelial thickness were significantly greater in Cnicus benedictus extract-loaded scaffolds than other groups. Gene expression studies showed that the produced wound dressings significantly upregulated VEGF and IGF genes expression in diabetic wounds.

Bipyridine-N,N'-dioxides Catalysts: Design, Synthesis, and Application in Asymmetric Synthesis of 1H-Pyrazolo[3,4-b]pyridine Analogues.

A novel type of highly efficient chiral C2-symmetric bipyridine-N,N'-dioxides ligand application in catalyzing Michael addition/Cyclization of 5-aminopyrazoles with α,ß-unsaturated 2-acyl imidazoles has been developed, affording the corresponding adducts in 85-97% yield with up to 99% enantioselectivity under mild conditions with a lower catalyst loading and broad scope. Remarkably, this protocol exhibits advantages in terms of reactivity and enantioselectivity, giving the fact that as low as 2.2 mol % of L1 and 2.0 mol % of Ni(OTf)2 can promote the title reaction on gram scale to afford the desired product with excellent enantioselectivity.

Utilizing daily excessive concentration hours to estimate small for gestational age infants attributable to fine particulate matter in Wuhan, China.

Limited studies in China have explored the association between gravidae exposure to PM2.5 and small for gestational age infants (SGA), yielding inconsistent results. This study in Wuhan utilized daily excessive concentration hours (DECH) as a novel measure to assess PM2.5's impact on SGA. Data on air pollutants and pregnant women were collected from the Wuhan Municipal Ecology and Environmental Bureau and Wuhan Children's Hospital, respectively. Logistic regression models were employed to evaluate the contribution of PM2.5-DECH and PM2.5-mean to SGA. Significant correlations were observed between PM2.5-mean and SGA during the second trimester [OR = 1.23 (95% CI: 1.14-1.32)] and the entire pregnancy [OR = 1.15 (95% CI: 1.07-1.24)]. Similar correlations were found between PM2.5-DECH and SGA. These findings suggest that increased PM2.5 exposure is associated with a higher risk of SGA, and DECH may be used as a prospective substitute indicator for daily average concentration in similar studies.

Swimming exercise reverses transcriptomic changes in aging mouse lens.

BACKGROUND: The benefits of physical activity for the overall well-being of elderly individuals are well-established, the precise mechanisms through which exercise improves pathological changes in the aging lens have yet to be fully understood. METHODS: 3-month-old C57BL/6J mice comprised young sedentary (YS) group, while aging mice (18-month-old) were divided into aging sedentary (AS) group and aging exercising (AE) group. Mice in AE groups underwent sequential stages of swimming exercise. H&E staining was employed to observe alterations in lens morphology. RNA-seq analysis was utilized to examine transcriptomic changes. Furthermore, qPCR and immunohistochemistry were employed for validation of the results. RESULTS: AE group showed alleviation of histopathological aging changes in AS group. By GSEA analysis of the transcriptomic changes, swimming exercise significantly downregulated approximately half of the pathways that underwent alterations upon aging, where notable improvements were 'calcium signaling pathway', 'neuroactive ligand receptor interaction' and 'cell adhesion molecules'. Furthermore, we revealed a total of 92 differentially expressed genes between the YS and AS groups, of which 10 genes were observed to be mitigated by swimming exercise. The result of qPCR was in consistent with the transcriptome data. We conducted immunohistochemical analysis on Ciart, which was of particular interest due to its dual association as a common aging gene and its significant responsiveness to exercise. The Protein-protein Interaction network of Ciart showed the involvement of the regulation of Rorb and Sptbn5 during the process. CONCLUSION: The known benefits of exercise could extend to the aging lens and support further investigation into the specific roles of Ciart-related pathways in aging lens.

Deciphering the Mechanism of Siwu Decoction Inhibiting Liver Metastasis by Integrating Network Pharmacology and In Vivo Experimental Validation.

BACKGROUND: Siwu Decoction (SWD) is a well-known classical TCM formula that has been shown to be effective as a basis for preventing and reducing liver metastases (LM). However, the active ingredients and potential molecular mechanisms remain unclear. OBJECTIVE: This study aimed to systematically analyze the active ingredients and potential molecular mechanisms of SWD on LM and validate mechanisms involved. MATERIALS AND METHODS: The active ingredients in SWD were extracted by UHPLC-MS/MS in a latest study. Protox II was retrieved to obtain toxicological parameters to detect safety. Swiss Target Prediction database was exploited to harvest SWD targets. Five databases, Gene Cards, DisGeNET, Drugbank, OMIM, and TTD, were employed to filter pathogenic targets of LM. STRING database was utilized to construct the protein-protein interaction network for therapeutic targets, followed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. GEPIA database and the Human Protein Atlas were taken to observe the expression of core genes and proteins. ImmuCellAI algorithm was applied to analyze the immune microenvironment and survival relevant to core genes. Molecular docking was performed to verify the affinity of SWD effective ingredients to core targets. In vivo experiments were carried out to validate the anti-LM efficacy of SWD and verify the pivotal mechanisms of action. RESULTS: Eighteen main bioactive phytochemicals identified were all non-hepatotoxic. PPI network acquired 118 therapeutic targets, of which VEGFA, CASP3, STAT3, etc. were identified as core targets. KEGG analysis revealed that HIF-1 pathway and others were critical. After tandem targets and pathways, HIF-1/VEGF was regarded as the greatest potential pathway. VEGFA and HIF-1 were expressed differently in various stages of cancer and normal tissues. There was a negative regulation of immunoreactive cells by VEGFA, which was influential for prognosis. Molecular docking confirmed the tight binding to VEGFA. This study revealed the exact effect of SWD against LM, and identified significant inhibition the expression of HIF-1α, VEGF, and CD31 in the liver microenvironment. CONCLUSION: This study clarified the active ingredients of SWD, the therapeutic targets of LM and potential molecular mechanisms. SWD may protect against LM through suppressing HIF-1/VEGF pathway.

Nomograms for assessing the rupture risk of anterior choroid artery aneurysms based on clinical, morphological, and hemodynamic features.

Background and purpose: A notable prevalence of subarachnoid hemorrhage is evident among patients with anterior choroidal artery aneurysms in clinical practice. To evaluate the risk of rupture in unruptured anterior choroidal artery aneurysms, we conducted a comprehensive analysis of risk factors and subsequently developed two nomograms. Methods: A total of 120 cases of anterior choroidal artery aneurysms (66 unruptured and 54 ruptured) from 4 medical institutions were assessed utilizing computational fluid dynamics (CFD) and digital subtraction angiography (DSA). The training set, consisting of 98 aneurysms from 3 hospitals, was established, with an additional 22 cases from the fourth hospital forming the external validation set. Statistical differences between the two data sets were thoroughly compared. The significance of 9 clinical baseline characteristics, 11 aneurysm morphology parameters, and 4 hemodynamic parameters concerning aneurysm rupture was evaluated within the training set. Candidate selection for constructing the nomogram models involved regression analysis and variance inflation factors. Discrimination, calibration, and clinical utility of the models in both training and validation sets were assessed using area under curves (AUC), calibration plots, and decision curve analysis (DCA). The DeLong test, net reclassification index (NRI), and integrated discrimination improvement (IDI) were employed to compare the effectiveness of classification across models. Results: Two nomogram models were ultimately constructed: model 1, incorporating clinical, morphological, and hemodynamic parameters (C + M + H), and model 2, relying primarily on clinical and morphological parameters (C + M). Multivariate analysis identified smoking, size ratio (SR), normalized wall shear stress (NWSS), and average oscillatory shear index (OSIave) as optimal candidates for model development. In the training set, model 1 (C + M + H) achieved an AUC of 0.795 (95% CI: 0.706 ~ 0.884), demonstrating a sensitivity of 95.6% and a specificity of 54.7%. Model 2 (C + M) had an AUC of 0.706 (95% CI: 0.604 ~ 0.808), with corresponding sensitivity and specificity of 82.4 and 50.3%, respectively. Similarly, AUCs for models 1 and 2 in the external validation set were calculated to be 0.709 and 0.674, respectively. Calibration plots illustrated a consistent correlation between model evaluations and real-world observations in both sets. DCA demonstrated that the model incorporating hemodynamic parameters offered higher clinical benefits. In the training set, NRI (0.224, p = 0.007), IDI (0.585, p = 0.002), and DeLong test (change = 0.089, p = 0.008) were all significant. In the external validation set, NRI, IDI, and DeLong test statistics were 0.624 (p = 0.063), 0.572 (p = 0.044), and 0.035 (p = 0.047), respectively. Conclusion: Multidimensional nomograms have the potential to enhance risk assessment and patient-specific treatment of anterior choroidal artery aneurysms. Validated by an external cohort, the model incorporating clinical, morphological, and hemodynamic features may provide improved classification of rupture states.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases: A case report.

BACKGROUND: Small cell lung cancer (SCLC) is a common and aggressive subtype of lung cancer. It is characterized by rapid growth and a high mortality rate. Approximately 10% of patients with SCLC present with brain metastases at the time of diagnosis, which is associated with a median survival of 5 mo. This study aimed to summarize the effect of bevacizumab on the progression-free survival (PFS) and overall survival of patients with brain metastasis of SCLC. CASE SUMMARY: A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks. The patient was diagnosed with limited-stage SCLC. He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo. CONCLUSION: The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Long-term trends in incidence, mortality and burden of liver cancer due to specific etiologies in Hubei Province.

Liver cancer, a chronic non-communicable disease, represents a serious public health problem. Long-term trends in the burden of liver cancer disease are heterogeneous across regions. Incidence and mortality of liver cancer, based on the Global Burden of Disease, were collected from the Chinese Centre for Disease Control and Prevention. Age-period-cohort model was utilized to reveal the secular trends and estimate the age, period and cohort effects on primary liver cancer due to specific etiologies. Both the age-standardized incidence and mortality rate of liver cancer in Hubei province were on the rise, although there were discrepancies between gender groups. From age-period-cohort analysis, both incidence and mortality of liver cancer due to Hepatitis B virus were the highest in all age groups. The incidence of all liver cancer groups increased with time period in males, while this upward trend was observed in females only in liver cancer due to alcohol use group. Cohort effects indicated the disease burden of liver cancer decreased with birth cohorts. Local drifts showed that the incidence of liver cancer due to specific etiologies was increasing in the age group of males between 40 and 75 years old. The impact of an aging population will continue in Hubei Province. the disease burden of liver cancer will continue to increase, and personalized prevention policies must be adopted to address these changes.

A Cu(â ¡)-eluting coating through silk fibroin film on ZE21B alloy designed for in situ endotheliazation biofunction.

In the cardiovascular field, coating containing copper used to catalyze NO (nitric oxide) production on non-degradable metal surfaces have shown unparalleled expected performance, but there are few studies on biodegradable metal surfaces. Magnesium-based biodegradable metals have been applied in cardiovascular field in large-scale because of their excellent properties. In this study, the coating of copper loaded in silk fibroin is fabricated on biodegradable ZE21B alloy. Importantly, the different content of copper is set to investigate the effects of on the degradation performance and cell behavior of magnesium alloy. Through electrochemical and immersion experiments, it is found that high content of copper will accelerate the corrosion of magnesium alloy. The reason is the spontaneous micro-batteries between copper and magnesium with the different standard electrode potentials, that is, the galvanic corrosion accelerates the corrosion of magnesium alloy. Moreover, the coating formed through silk fibroin by the right amount copper not only have a protective effect on the ZE21B alloy substrate, but also promotes the adhesion and proliferation of endothelial cells in blood vessel micro-environment. The production of NO catalyzed by copper ions makes this trend more significant, and inhibits the excessive proliferation of smooth muscle cells. These findings can provide guidance for the amount of copper in the coating on the surface of biodegradable magnesium alloy used for cardiovascular stent purpose.

Colorectal cancer and its attributable risk factors in East Asia, 1990-2030.

BACKGROUND: The disease burden of colorectal cancer in East Asia has been at a high level. However, the epidemiological characteristics of the disease burden in this region have not been systematically studied. METHOD: Data were obtained from the Global Burden of Disease 2019 program. Joinpoint analysis was used to identify long-term trends in mortality of colorectal cancer. Independent effects of age, period, and cohort were detected by the age-period-cohort model. The Bayesian age-period-cohort model was performed to predict the burden of colorectal cancer across East Asia by 2030. RESULTS: From 1990 to 2019, the average annual percentage change (AAPC) showed upward trends in mainland China (1.05 [95% confidence interval (CI)], 0.82, 1.28) as well as Taiwan Province of China (1.81 [95% CI], 1.51, 2.10) but downward in Japan (-0.60 [95% CI], -0.70, -0.49) (P < 0.05). Attributable risk factors for colorectal cancer in East Asia remained stable over 30 years, while the risk of metabolic factors is noteworthy in the future. In the next decade, the age-standardized death rate (ASDR) of colorectal cancer in China was predicted to surpass that of Japan and South Korea in expectation. CONCLUSION: The mortality of colorectal cancer is escalating in developing countries, while it is gradually declining in high-income countries across East Asia. Nonetheless, the disease burden of colorectal cancer in high-income countries remains substantial level.

Review of pre-metastatic niches in lung metastasis: From cells to molecules, from mechanism to clinics.

Distant metastasis is responsible for high mortality in most cancer cases and the lung is one of the most common target organs, severely affecting the quality of daily life and overall survival of cancer patients. With relevant research breakthroughs accumulating, scientists have developed a deeper understanding of lung metastasis (LM) from the rudimentary "seed and soil" theory to a more vivid concept of the pre-metastatic niche (PMN). Thus, the mechanisms of PMN formation become considerably complicated, involving various types of cells, chemokines, cytokines, and proteins, providing potential biomarkers for improved LM diagnosis and treatment techniques. Here we summarized the latest findings (in 3 years) of lung PMN and systematically collated it from basic research to clinical application, which clearly exhibited the influences of the primary tumor, stromal, and bone marrow-derived cells (BMDCs) and associated molecules in the formation of lung PMN.

Performance of a non-irrigated bipolar radiofrequency ablation clamp on beating human hearts.

OBJECTIVE: This study is intended to examine the efficacy of a non-irrigated bipolar RF clamp and explore the factors that can influence its performance on beating human hearts using the electrophysiology mapping method. METHODS: A total of 83 atrial fibrillation (AF) patients were included in this study. Based on the Body mass index (BMI, kg/m2), the AF patients were divided into the normal group (18.5 ≤ BMI < 25) and the overweight or obese group (BMI ≥ 25). They all underwent a stand-alone surgical ablation through our off-pump biatrial mini-maze procedure. After we completed each time of ablation, the achievement of PV isolation was checked using the electrophysiology mapping method. The number of ablation times to achieve the PV isolation on the left and right PVs was recorded respectively. RESULTS: 86.7% (72/83) PV isolation on the LPV and 72.3% (60/83) PV isolation on the RPV could be achieved respectively after performing a single time of surgical ablation. Three times of ablations resulted in 100.0% PV isolation on the left and right PVs. In the normal BMI group, the ratio of patients who achieved a complete PV isolation after a single time of ablation was 83.7% (36/43), which was higher than the 60.0% (24/40) in the overweight or obese group. CONCLUSIONS: Performing three times of ablations resulted in 100% PV isolation on the left and right PVs. The bipolar RF clamp had a better performance on the LPV than on the RPV. The patients' BMI also influenced the Atricure clamp' s performance.

Global, regional and national burden of ischemic stroke attributed to high low-density lipoprotein cholesterol, 1990-2019：A decomposition analysis and age-period-cohort analysis.

High levels of low-density lipoprotein cholesterol (LDL-C) have been associated with an augmented mortality of ischemic stroke. The yearly deaths and mortality data of IS-hLDL-C were derived from the global burden of disease 2019 dataset. The joinpoint, age-period-cohort and decomposition analysis were utilized to evaluate the long-term patterns in the disease burden of IS-hLDL-C, and the effects of population growth and aging. Globally, in 2019, 0.61 million ischemic stroke-related deaths were attributable to high LDL-C, with the highest death burden in the high-middle socio-demographic index (SDI) region. From 1990 to 2019, the age-standardized death rate (ASDR) for IS-hLDL-C exhibited a downward trend, with an average annual percentage change of -1.69 [95% confidence interval: -1.90, -1.48)]. The fastest decreasing trends in ASDR were experienced in the high SDI region. In 119 (58.33%) countries, aging increased the disease burden of hLDL-IS, and population growth increased the disease burden of IS-hLDL-C in 163 (79.90%) countries. The trend in disease burden of IS-hLDL-C exhibited variation across countries and regions, particularly in territories with high to middle high SDI. Aging in upper to middle-income countries and population growth in low to middle-income countries further offset endeavors to reduce the burden of ischemic stroke deaths.

Global burden of non-optimal temperature attributable stroke: The long-term trends, population growth and aging effects.

Since the 20th century, the world has undergone climate change, population growth and population aging, which may result in alterations in the epidemiology of non-optimal temperature-associated strokes. We employed multiple methodologies and data from the global burden of disease 2019 to unveil the long-term curvilinear trends in strokes attributed to non-optimal temperature and the impact of aging and population growth on its changing epidemiology. From 1990 to 2019, the age-standardized DALYs rate (ASDR) of strokes attributable to low temperature had been decreasing, but from 2016, the continued downward trend in ASDR disappeared and began to remain stable. On the contrary, the ASDR of strokes attributable to high temperature continued to increase. The high socio-demographic index (SDI) region experienced the fastest decreased trend. The disease burden of stroke attributable to low temperature is increased by aging in 178 countries (87.25%), compared with 130 (63.73%) for high temperature. After excluding aging and population growth, the DALY rate for strokes attributed to high temperature was increasing in 87 countries and territories (42.64%). The disease burden of strokes attributed to low temperature is far greater than that of high temperature in absolute figures. However, globally, there is a significant trend toward an increase in strokes attributed to high temperature. Social development has largely offset the burden of strokes attributed to low temperature, but most regions of the world are equally affected by strokes attributed to high temperature. Simultaneously, in the framework of climate change, aging is also largely hindering stroke prevention efforts.

Finite element modeling and analysis of effect of preexisting cervical degenerative disease on the spinal cord during flexion and extension.

Recent studies have emphasized the importance of dynamic activity in the development of myelopathy. However, current knowledge of how degenerative factors affect the spinal cord during motion is still limited. This study aimed to investigate the effect of various types of preexisting herniated cervical disc and the ligamentum flavum ossification on the spinal cord during cervical flexion and extension. A detailed dynamic fluid-structure interaction finite element model of the cervical spine with the spinal cord was developed and validated. The changes of von Mises stress and maximum principal strain within the spinal cord in the period of normal, hyperflexion, and hyperextension were investigated, considering various types and grades of disc herniation and ossification of the ligamentum flavum. The flexion and extension of the cervical spine with spinal canal encroachment induced high stress and strain inside the spinal cord, and this effect was also amplified by increased canal encroachments and cervical hypermobility. The spinal cord might evade lateral encroachment, leading to a reduction in the maximum stress and principal strain within the spinal cord in local-type herniation. Although the impact was limited in the case of diffuse type, the maximum stress tended to appear in the white matter near the encroachment site while compression from both ventral and dorsal was essential to make maximum stress appear in the grey matter. The existence of canal encroachment can reduce the safe range for spinal cord activities, and hypermobility activities may induce spinal cord injury. Besides, the ligamentum flavum plays an important role in the development of central canal syndrome.Significance. This model will enable researchers to have a better understanding of the influence of cervical degenerative diseases on the spinal cord during extension and flexion.