A Cyclometalated Ruthenium(II) Complex Induces Oncosis for Synergistic Activation of Innate and Adaptive Immunity.

An optimal cancer chemotherapy regimen should effectively address the drug resistance of tumors while eliciting antitumor-immune responses. Research has shown that non-apoptotic cell death, such as pyroptosis and ferroptosis, can enhance the immune response. Despite this, there has been limited investigation and reporting on the mechanisms of oncosis and its correlation with immune response. Herein, we designed and synthesized a Ru(II) complex that targeted the nucleus and mitochondria to induce cell oncosis. Briefly, the Ru(II) complex disrupts the nucleus and mitochondria DNA, which active polyADP-ribose polymerase 1, accompanied by ATP consumption and porimin activation. Concurrently, mitochondrial damage and endoplasmic reticulum stress result in the release of Ca2+ ions and increased expression of Calpain 1. Subsequently, specific pore proteins porimin and Calpain 1 promote cristae destruction or vacuolation, ultimately leading to cell membrane rupture. The analysis of RNA sequencing demonstrates that the Ru(II) complex can initiate the oncosis-associated pathway and activate both innate and adaptive immunity. In vivo experiments have confirmed that oncosis promotes dendritic cell maturation and awakens adaptive cytotoxic T lymphocytes but also activates the innate immune by inducing the polarization of macrophages towards an M1 phenotype.

Impact of healthy lifestyle on the incidence and progression trajectory of mental disorders: A prospective study in the UK Biobank.

BACKGROUND: Healthier lifestyle decreased the risk of mental disorders (MDs) such as depression and anxiety. However, research on the effects of a comprehensive healthy lifestyle on their progression is lacking. METHODS: 385,704 individuals without baseline MDs from the UK Biobank cohort were included. A composite healthy lifestyle score was computed by assessing alcohol intake, smoking status, television viewing time, physical activity, sleep duration, fruit and vegetable intake, oily fish intake, red meat intake, and processed meat intake. Follow-up utilized hospital and death register records. Multistate model was used to examine the role of healthy lifestyle on the progression of specific MDs, while a piecewise Cox regression model was utilized to assess the influence of healthy lifestyle across various phases of disease progression. RESULTS: Higher lifestyle score reduced risks of transitions from baseline to anxiety and depression, as well as from anxiety and depression to comorbidity, with corresponding hazard ratios (HR) and 95 % confidence intervals (CI) of 0.94 (0.93, 0.95), 0.90 (0.89, 0.91), 0.94 (0.91, 0.98), and 0.95 (0.92, 0.98), respectively. Healthier lifestyle decreased the risk of transitioning from anxiety to comorbidity within 2 years post-diagnosis, with HR 0.93 (0.88, 0.98). Higher lifestyle scores at 2-4 years and 4-6 years post-depression onset were associated with reduced risk of comorbidity, with HR 0.93 (0.87, 0.99) and 0.92 (0.86, 0.99), respectively. LIMITATION: The generalizability to other ethnic groups is limited. CONCLUSION: This study observed a protective role of holistic healthy lifestyle in the trajectory of MDs and contributed to identifying critical progression windows.

A Mitochondria-Targeted Nitric Oxide Probe for Multimodality Imaging of Macrophage Immune Responses.

Nitric oxide (NO) is a crucial signal molecule closely linked to the biological immune response, especially in macrophage polarization. When activated, macrophages enter a pro-inflammatory state and produce NO, a marker for the M1 phenotype. In contrast, the anti-inflammatory M2 phenotype does not produce NO. We developed a mitochondria-targeted two-photon iridium-based complex (Ir-ImNO) probe that can detect endogenous NO and monitor macrophages' different immune response states using various imaging techniques, such as one- and two-photon phosphorescence imaging and phosphorescence lifetime imaging. Ir-ImNO was used to monitor the immune activation of macrophages in mice. This technology aims to provide a clear and comprehensive visualization of macrophage immune responses.

Microvascular disease, modifiable risk factor profiles and incident arrhythmias in type 2 diabetes.

BACKGROUND: To assess the roles of diabetic microvascular disease and modifiable risk factors and their combination in the development of arrhythmias. METHODS: We included participants with type 2 diabetes (T2D) who were free of arrhythmias during recruitment in the UK Biobank study. The associations of microvascular disease states (defined by the presence of retinopathy, peripheral neuropathy or chronic kidney disease), four modifiable arrhythmic risk factors (body mass index, smoking, systolic blood pressure and glycosylated haemoglobin) and their joint associations with incident arrhythmias were examined. RESULTS: Among the 25 632 participants with T2D, 1705 (20.1%) of the 8482 with microvascular disease and 2017 (11.8%) of the 17 150 without microvascular disease developed arrhythmias during a median follow-up of 12.3 years. Having any of the three microvascular diseases was associated with a 48% increase in the hazard of developing arrhythmias. Incorporating microvascular disease states into a model alongside 11 traditional risk factors significantly enhanced arrhythmia prediction. Furthermore, individuals with microvascular disease who had optimal levels of zero to one, two, three or four arrhythmic risk factors showed an HR of 2.05 (95% CI 1.85, 2.27), 1.67 (95% CI 1.53, 1.83), 1.35 (95% CI 1.22, 1.50) and 0.91 (95% CI 0.73, 1.13), respectively, compared with those without microvascular disease. CONCLUSIONS: Although microvascular disease, a non-traditional risk factor, was associated with incident arrhythmias in individuals with T2D, having optimal levels of risk factors may mitigate this risk.

Nanocatalysts for modulating antitumor immunity: fabrication, mechanisms and applications.

Immunotherapy harnesses the inherent immune system in the body to generate systemic antitumor immunity, offering a promising modality for defending against cancer. However, tumor immunosuppression and evasion seriously restrict the immune response rates in clinical settings. Catalytic nanomedicines can transform tumoral substances/metabolites into therapeutic products in situ, offering unique advantages in antitumor immunotherapy. Through catalytic reactions, both tumor eradication and immune regulation can be simultaneously achieved, favoring the development of systemic antitumor immunity. In recent years, with advancements in catalytic chemistry and nanotechnology, catalytic nanomedicines based on nanozymes, photocatalysts, sonocatalysts, Fenton catalysts, electrocatalysts, piezocatalysts, thermocatalysts and radiocatalysts have been rapidly developed with vast applications in cancer immunotherapy. This review provides an introduction to the fabrication of catalytic nanomedicines with an emphasis on their structures and engineering strategies. Furthermore, the catalytic substrates and state-of-the-art applications of nanocatalysts in cancer immunotherapy have also been outlined and discussed. The relationships between nanostructures and immune regulating performance of catalytic nanomedicines are highlighted to provide a deep understanding of their working mechanisms in the tumor microenvironment. Finally, the challenges and development trends are revealed, aiming to provide new insights for the future development of nanocatalysts in catalytic immunotherapy.

Microvascular Disease, Cardiovascular Health, and Risk of Coronary Heart Disease in Type 2 Diabetes: A UK Biobank Study.

CONTEXT: The interplay between cardiovascular health metrics (CVHMs) and microvascular disease (MVD) in relation to the risk of incident coronary heart disease (CHD) among individuals with type 2 diabetes mellitus (T2DM) remains to be evaluated. OBJECTIVE: To investigate the role of MVD and CVHMs in the development of CHD among T2DM. DESIGN: We included 19,664 participants with T2DM from the UK Biobank who had data on CVH metrics (CVHMs) and were free of CHD during recruitment. CVHMs were defined based on five behavioral (body mass index, diet, sleep duration, smoking, and regular exercise) and three biological factors (glycemic control, hyperlipidemia, and hypertension). MVD was defined as the presence of retinopathy, peripheral neuropathy, and chronic kidney disease. HR and 95% CI of CHD were estimated by multivariable Cox regression models. RESULTS: There were 3,252 incident cases of CHD recorded after a median follow-up of 12.3 years. After multivariable adjustment, each MVD was separately associated with risk of CHD, and those who had 1 or ≥2 MVD had a 27% and an 87% increased risk of developing CHD, respectively. Each of the unfavorable CVHMs was associated with a higher risk of CHD. As compared with MVD-free participants who had ideal CVHMs, those who had ≥2 MVD and had poor CVHMs were at particularly high risk of incident CHD (HR=4.58; 95% CI: 3.58, 5.86), similarly when considering behavioral CVH or biological CVH separately. On an additive scale, there was a positive statistically significant interaction between number of MVD and CVHMs. CONCLUSIONS: Coexistence of multiple MVDs was associated with a substantially higher risk of CHD among individuals with T2DM. Such an association may be amplified by unfavorable CVHMs.

Associations of blood biomarkers with arterial stiffness in patients with diabetes mellitus: A population-based study.

BACKGROUND: Arterial stiffness contributes to additional cardiovascular risks in diabetic patients by triggering the loss of vascular and myocardial compliance and promoting endothelial dysfunction. Thus, prevention of arterial stiffness is a public health priority, and the identification of potential biomarkers may provide benefits for early prevention. This study investigates the relationships between serum laboratory tests and pulse wave velocity (PWV) tests. We also investigated the associations between PWV and all-cause mortality. METHODS: We examined a panel of 33 blood biomarkers among diabetic populations in the Atherosclerosis Risk in Communities Study. The carotid-femoral (cfPWV) and femoral-ankle PWV (faPWV) were measured using an automated cardiovascular screening device. The aortic-femoral arterial stiffness gradient (afSG) was calculated as faPWV divided by cfPWV. Biomarker levels were log-transformed and correlated with PWV. Cox proportional hazard models were employed for survival analysis. RESULTS: Among 1079 diabetic patients, biomarkers including high-density lipoprotein cholesterol, glycated hemoglobin, high-sensitivity troponin T, cystatin C, creatinine, and albuminuria were significantly correlated with afSG (R = 0.078, -0.193, -0.155, -0.153, -0.116, and -0.137, respectively) and cfPWV (R = -0.068, 0.175, 0.128, 0.066, 0.202, and 0.062, respectively). Compared with the lowest tertile of afSG, the risk of all-cause mortality was lower in the highest tertile (hazard ratio 0.543; 95% confidence interval 0.328-0.900). CONCLUSION: Certain biomarkers related to blood glucose monitoring, myocardial injury, and renal function significantly correlated with PWV, suggesting that these putative risk factors are likely to be important atherosclerosis mechanisms in diabetic patients. AfSG may be an independent predictor of mortality among diabetic populations.

The independent and joint association of accelerometer-measured physical activity and sedentary time with dementia: a cohort study in the UK Biobank.

BACKGROUND: Research on the association of physical activity and sedentary time with dementia is accumulating, though elusive, and the interaction effects of the two remain unclear. We analysed the joint associations of accelerometer-measured physical activity and sedentary time with risk of incident dementia (all-cause dementia, Alzheimer's disease and vascular dementia). METHODS: A total of 90,320 individuals from the UK Biobank were included. Accelerometer-measured total volume of physical activity (TPA) and sedentary time were measured at baseline and dichotomised by median (low TPA [< 27 milli-gravity (milli-g)], high TPA [≥ 27 milli-g]; low sedentary time [< 10.7 h/day], high sedentary time [≥ 10.7 h/day]). Cox proportional hazards models were used to evaluate the joint associations with incident dementia on both additive and multiplicative scales. RESULTS: During a median follow-up of 6.9 years, 501 cases of all-cause dementia were identified. Higher TPA was associated with a lower risk of all-cause dementia, Alzheimer's disease and vascular dementia; the multivariate adjusted hazard ratios (HRs) (95% CI) per 10 milli-g increase were 0.63 (0.55-0.71), 0.74 (0.60-0.90) and 0.69 (0.51-0.93), respectively. Sedentary time was only found to be linked to all-cause dementia, and the HR for high sedentary time was 1.03 (1.01-1.06) compared with that for low sedentary time. No additive and multiplicative relationship of TPA and sedentary time to incident dementia was found (all P values > 0.05). CONCLUSION: Higher TPA level was related to a lower risk of incident dementia irrespective of sedentary time, which highlighted the implication of promoting physical activity participation to counteract the potential detrimental effect of sedentary time on dementia.

The Association Between Exposure to Air Pollution and Dementia Incidence: The Modifying Effect of Smoking.

BACKGROUND: The influence of overall air pollution on dementia risk and the potential effect modification by other risk factors remain to be clarified. METHODS: We included 459 844 UK residents who were free of dementia and had data on the exposure to particulate matter (PM)2.5, PM2.5-10, PM10, NO2, and NOx during baseline recruitment. The combined exposure to various PMs and NOx was estimated by using an air pollution score. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia were estimated by multivariable Cox models. RESULTS: During a median 11.7 years follow-up, 5 905 incident cases of all-cause dementia were identified. With the exception of PM2.5-10, all other air pollutants were separately associated with a higher risk of all-cause dementia (all p-trend < .001) with generally similar associations for dementia subtypes. An increasing air pollution score was associated with higher risks of all-cause as well as individual dementia outcomes, with adjusted HRs (95% CI) of 1.27 (1.18, 1.37) for all-cause dementia, 1.27 (1.14, 1.43) for Alzheimer's disease, and 1.35 (1.16, 1.57) for vascular dementia when comparing the highest with the lowest quartile of the score (all p-trend < .001). These associations of air pollution score with dementia and its subtypes were observed among never and former smokers but not among current smokers (all p-interaction < .030). CONCLUSION: Air pollution was associated with a higher risk of dementia among nonsmokers but not current smokers. Additional studies are required to confirm our findings and to explore the potential mechanisms underlying the possible effect modification by smoking status.

Cold Nanozyme for Precise Enzymatic Antitumor Immunity.

Precise catalysis is pursued for the biomedical applications of artificial enzymes. It is feasible to precisely control the catalysis of artificial enzymes via tunning the temperature-dependent enzymatic kinetics. The safety window of cold temperatures (4-37 °C) for the human body is much wider than that of thermal temperatures (37-42 °C). Although the development of cold-activated artificial enzymes is promising, there is currently a lack of suitable candidates. Herein, a cold-activated artificial enzyme is presented with Bi2Fe4O9 nanosheets (NSs) as a paradigm. The as-obtained Bi2Fe4O9 NSs possess glutathione oxidase (GSHOx)-like activity under cold temperature due to their pyroelectricity. Bi2Fe4O9 NSs trigger the cold-enzymatic death of tumor cells via apoptosis and ferroptosis, and minimize the off-target toxicity to normal tissues. Moreover, an interventional device is fabricated to intelligently and remotely control the enzymatic activity of Bi2Fe4O9 NSs on a smartphone. With Bi2Fe4O9 NSs as an in situ vaccine, systemic antitumor immunity is successfully activated to suppress tumor metastasis and relapse. Moreover, blood biochemistry analysis and histological examination indicate the high biosafety of Bi2Fe4O9 NSs for in vivo applications. This cold nanozyme provides a strategy for cancer vaccines, which can benefit the precise control over catalytic nanomedicines.

Cold-catalytic antitumor immunity with pyroelectric black phosphorus nanosheets.

Catalytic nanomedicine with the innate features of catalysts brings incomparable properties to biomedicine over traditional drugs. The temperature-dependent activity of catalysts provides catalytic nanomedicines with a facile strategy to control their therapeutic performance. Tuning catalytic nanomedicine by cold treatment (4-37 °C) is safe and desired for practical applications, but there is a lack of cold-catalytic platforms. Herein, with black phosphorus (BP) as a model pyroelectric nanocatalyst, we explored the potential of cold-catalysts for antitumor therapy. BP nanosheets with pyro-catalytic activity catalyze the generation of oxidative stress to activate antitumor immunity under cold treatment. Due to the cold-catalytic immunomodulation, immune memory was successfully achieved to prevent tumor metastasis and recurrence. Considering the safety and conductive depth (>10 mm) of cold in the body, pyroelectric nanocatalysts open up exciting opportunities for the development of cold-catalytic nanomedicine.

Long-term exposure to air pollution and risk of incident inflammatory bowel disease among middle and old aged adults.

BACKGROUND: Epidemiological evidence regarding the associations between long-term exposure to air pollution and risk of incident inflammatory bowel disease (IBD) is scant. OBJECTIVES: We examined the associations of various specific air pollutants with the risk of incident ulcerative colitis and Crohn's disease, two subtypes of IBD, among middle and old aged adults in the UK. We also explored potential susceptible subgroups. METHODS: We used data from the UK Biobank study. Information on air pollution, including PM2.5, PM2.5-10, PM10 as well as NO2 and NOx were estimated using the Land Use Regression model. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a median follow-up of 11.7 years, 1872 incident ulcerative colitis and 865 incident Crohn's disease cases were identified among 455,210 IBD-free participants. HRs (95% CIs) of ulcerative colitis associated with each 1 interquartile range (IQR) increase in PM2.5, PM2.5-10, PM10, NO2, and NOx were 1.06 (1.01, 1.12), 1.03 (0.99, 1.08), 1.09 (1.03, 1.16), 1.12 (1.07, 1.19), and 1.07 (1.02, 1.12), respectively. The associations between all the air pollutants and risk of Crohn's disease were null. Smoking status and sex appeared to respectively modify the associations between some air pollutants and risk of ulcerative colitis and Crohn's disease. CONCLUSION: Long-term exposure to various air pollutants was associated with the risk of incident ulcerative colitis but not Crohn's disease, highlighting the importance of developing environmental health strategy to reduce the burden of ulcerative colitis.

Favourable Lifestyle Protects Cognitive Function in Older Adults With High Genetic Risk of Obesity: A Prospective Cohort Study.

The relationship between body mass index (BMI) and cognitive impairment remains controversial, especially in older people. This study aims to confirm the association of phenotypic and genetic obesity with cognitive impairment and the benefits of adhering to a healthy lifestyle. This prospective study included 10,798 participants (aged ≥ 50 years) with normal cognitive function from the Health and Retirement Study in the United States. Participants were divided into low (lowest quintile), intermediate (quintiles 2-4), and high (highest quintile) groups according to their polygenic risk score (PRS) for BMI. The risk of cognitive impairment was estimated using Cox proportional hazard models. Higher PRS for BMI was associated with an increased risk, whereas phenotypic obesity was related to a decreased risk of cognitive impairment. Never smoking, moderate drinking, and active physical activity were considered favourable and associated with a lower risk of cognitive impairment compared with current smoking, never drinking, and inactive, respectively. A favourable lifestyle was associated with a low risk of cognitive impairment, even in subjects with low BMI and high PRS for BMI. This study suggest that regardless of obesity status, including phenotypic and genetic, adhering to a favourable lifestyle is beneficial to cognitive function.

Biocomputation with MnTiO3 Piezoelectric Enzymes for Programed Catalysis of Tumor Death.

Catalytic nanomedicine, especially artificial enzymes, exhibit obvious merits over traditional nanomedicine. However, the lack of controllability over an enzymatic process seriously challenges the therapeutic performance. Herein, we present a concept of using piezoelectric enzymes in combination with biocomputation ability. As a paradigm, MnTiO3 nanodisks were prepared with multiple enzyme-mimicking activity, including glutathione oxidase, peroxidase, and catalase. Different from the conventional artificial enzymes, the enzymatic activity of MnTiO3 nanodisks was activated by ultrasound and switched by a tumor microenvironment, which allows precise control over enzymatic catalysis in tumors. By virtue of the multiple artificial enzyme activity of MnTiO3 nanodisks, a biocomputing platform was constructed based on a Boolean logic-based algorithm. With ultrasound and tumor microenvironment as input signals, cytotoxicity was output via logic-based biocomputation for programed tumor killing. The concept of piezoelectric enzymes together with a biocomputation strategy provides an intelligent and effective approach for catalytic tumor eradication.

Recent Advances in Dual PI3K/mTOR Inhibitors for Tumour Treatment.

The PI3K-Akt-mTOR pathway is a viable target for cancer treatment and can be used to treat various malignant tumours, including follicular lymphoma and breast cancer. Both enzymes, PI3K and mTOR, are critical in this pathway. Hence, in recent years, an array of inhibitors targeting these two targets have been studied, showing dual PI3K/mTOR inhibition compared with single targeting small molecule inhibitors. Inhibitors not only inhibit cell proliferation but also promote cell apoptosis. These inhibitors show high potency and little drug resistance even at low doses, suggesting that PI3K/mTOR inhibitors are promising cancer drugs. Herein, we summarised the recent research of PI3K/mTOR dual inhibitors-for example, structure-activity relationship, pharmacokinetics, and clinical practice, and briefly commented on them. Clinical Trial Registration: https://clinicaltrials.gov.

Recent progress on FAK inhibitors with dual targeting capabilities for cancer treatment.

Focal adhesion kinase (FAK, also known as PTK2) is a tyrosine kinase that regulates integrin and growth factor signaling pathways and is involved in the migration, proliferation and survival of cancer cells. FAK is a promising target for cancer treatment. Many small molecule FAK inhibitors have been identified and proven in both preclinical and clinical studies to be effective inhibitors of tumor growth and metastasis. There are many signaling pathways, such as those involving FAK, Src, AKT, MAPK, PI3K, and EGFR/HER-2, that provide survival signals in cancer cells. Dual inhibitors that simultaneously block FAK and another factor can significantly improve efficacy and overcome some of the shortcomings of single-target inhibitors, including drug resistance. In this review, the antitumor mechanisms and research status of dual inhibitors of FAK and other targets, such as Pyk2, IGF-IR, ALK, VEGFR-3, JAK2, EGFR, S6K1, and HDAC2, are summarized, providing new ideas for the development of effective FAK dual-target preparations.

Associations Between High-Sensitivity C-Reactive Protein and All-Cause Mortality Among Oldest-Old in Chinese Longevity Areas: A Community-Based Cohort Study.

BACKGROUND: The association between high-sensitivity C-reactive protein (hsCRP) levels and all-cause mortality for the oldest-old (aged 80 years or older) remains unclear. We aimed to investigate the associations between hsCRP concentrations and the risks of all-cause mortality, and further identify the potential modifying factors affecting these associations among the oldest-old. METHODS: This prospective, community-based cohort study included 2,206 participants aged 80 years or older (median age 93.0 years) from the Healthy Aging and Biomarkers Cohort Study. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (95% CIs) for all-cause mortality according to hsCRP quartiles and recommendation for relative risk categories of hsCRP levels (< 1.0, 1.0-3.0, and > 3.0 mg/L), with adjustment for sociodemographic information, lifestyle, physical examination, medical history, and other potential confounders. RESULTS: During a median follow-up period of 3.1 years (IQR: 1.6-3.9 years), 1,106 deaths were verified. After full adjustment for potential confounders, a higher hsCRP concentration was positively associated with an increased risk of all-cause mortality (P for trend < 0.001). Compared with the lowest quartile, the fully adjusted HRs of the second, third, and fourth quartiles were 1.17 (95% CI: 0.94, 1.46), 1.28 (95% CI: 1.01, 1.61), and 1.49 (95% CI: 1.20, 1.87), respectively. The association of hsCRP with all-cause mortality was modified by smoking status (P for interaction = 0.011), an increased risk of hsCRP with all-cause mortality showed among non-current smokers (HR: 1.17; 95% CI: 1.07, 1.28), but no significance was observed in current smokers (HR: 0.83; 95% CI: 0.66, 1.18). CONCLUSIONS: Our study indicated that elevated hsCRP concentrations were associated with a higher risk of all-cause mortality among Chinese oldest-old. Future studies investigating additional factors of disease and aging processes are needed to obtain a better understanding of the mechanisms.

Knowledge framework and emerging trends in intracranial aneurysm magnetic resonance angiography: a scientometric analysis from 2004 to 2020.

BACKGROUND: As magnetic resonance angiography (MRA) has been increasingly used in the follow-up of intracranial aneurysms (IAs) as a non-invasive technique, the knowledge framework and areas of research interest in intracranial aneurysms magnetic resonance angiography (IAMRA) change approximately every 10 years. However, few studies have quantitatively analyzed the published literature in this field. In the present study, we used scientometrics to survey the knowledge field, development trends, and research focus of IAMRA with the aim of providing a reference for further study. METHODS: We collected articles on IAMRA published from 2004 (Jan 1, 2004) to 2020 (May 24, 2020). Web of Science Core Collection databases (WoSCCd) including the Science Citation Index Expanded were searched. An experienced staff member from the Department of Radiology at Southern Medical University, assisted in screening articles for relevant articles. We used ArcGIS (a mapping and location analytics platform) to perform geographic visualization. Excel 2016 was used to analyze the literature data, including number of publications, impact factor (IF), and publication year. CiteSpace V was used to conduct a series of literature feature clustering, including author co-citation analysis, reference co-citation analysis (RCA), and burst keywords analysis. RESULTS: A total of 1,272 articles on IAMRA published between 2004 and 2020 were included. Of 257 journals, American Journal of Neuroradiology (IF 2018: 3.256) published the most IAMRA articles (109 publications, 8.57%), followed by Journal of Neurosurgery (IF 2018: 4.131, 51 publications, 4.16%), and Neuroradiology (IF 2018: 2.504, 51 publications, 4.01%). Of 56 countries, the USA published the most, with 347 articles [27.28%, IF: 3.14 (average IF of all journals in the country)], followed by Japan (242 articles, 19.03%, IF: 2.38), Germany (135 articles, 10.61%, IF: 3.21), and China (101 articles, 7.94%, IF: 2.86). A total of 1387 institutions published articles, with the Mayo Clinic publishing the most (33 articles, 2.59%), followed by Shanghai Jiao Tong University (25 article, 1.97%), Seoul National University (23 articles, 1.81%), and University Medical Center Utrecht (19 articles, 1.49%). Of 399 authors, Rinkel ranked first with 19 articles, followed by Li MH (18 articles), Uchino A (15 articles), and Saito N (13 articles). Cluster RCA showed that the first cluster was "#0 growth", followed by "#1 Guglielmi detachable coils". Timeline views showed that the time span of "#0 growth" was the closest to today. The modularity value was 0.6971, and the mean silhouette value was 0.5477. According to the burst keyword analysis, "risk factors associated to rupture" was the topic with the strongest burst since 2017. Studies conducted in several countries suggested that age is inversely related to the risk of rupture, which implies the importance of MRA follow-up for patients of different age. CONCLUSIONS: From 2004 to 2020, the number of published IAMRA-related articles gradually increased. The USA and Western Europe lead in the field, with a concentration of cutting-edge talents and high-level scientific research institutions. A synthesis of the clustering results of RCA and burst keyword analysis indicated that unruptured IA growth, stent-assisted coil embolization, and risk factors associated to rupture were the current hotspots in IAMRA research.

Diabetes Treatment Is Associated With Better Cognitive Function: The Age Disparity.

Background: Diabetes mellitus (DM) is a recognised risk factor for cognitive dysfunction. The purpose of this study was to explore the relationship between active treatment for DM and cognitive function in middle-aged (< 60 years) and older adults (≥60 years), respectively. Methods: A total of 13,691 participants (58.55 ± 9.64 years, 47.40% of men) from the Chinese Health and Retirement Longitudinal Study (CHARLS) were included. The participants were classified into three groups according to whether or not they have diabetes and to their diabetes treatment status: diabetes-free, treated-diabetes and untreated-diabetes, in which the diabetes-free group was regarded as reference specially. Cognitive function was assessed by two interview-based measurements for mental intactness and episodic memory. Results: Compared with the participants in the diabetes-free group, the older participants in the treated-diabetes group had better performance in terms of mental intactness (ß = 0.37, 95% CI = 0.04-0.70). No significant association was observed in the middle-aged participants. In the subgroup analyses, the lower cognitive score was only observed in people without depression, who had never smoked and drunk, and with a normal weight (body mass index: 18.5-23.9 kg/m2). Conclusion: The cognitive function of actively treated diabetic patients was better than that of patients without diabetes, but the improvement was significant only in elderly people. Depression, smoking, drinking, and an abnormal weight may attenuate this effect.