Trend analysis of stroke subtypes mortality attributable to high body-mass index in China from 1990 to 2019.

BACKGROUND: The prevalence of stroke disability associated with high BMI has significantly increased over the past three decades. However, it remains uncertain whether high body-mass index (BMI) exerts a similar impact on the disease burden of different stroke subtypes. The aim of this study is to assess the long-term trends of stroke and subtypes mortality attributable to high BMI in China between 1990 and 2019. METHODS: Data on stroke and subtypes mortality attributable to high BMI in China was extracted in the Global Burden of Disease (GBD) 2019. The trends of age-standardized mortality rate (ASMR) were calculated using the linear regression and age-period-cohort framework. RESULTS: The changing trend of ASMR on stroke attributable to high BMI in China differed among subtypes, with an estimated annual percentage change (EAPC) and 95%CI of 2.04 (1.86 to 2.21) for ischemic stroke (IS), 0.36 (-0.03 to 0.75) for intracerebral hemorrhage (ICH), and - 4.62 (-5.44 to -3.78) for subarachnoid hemorrhage (SAH). Net and local drift analyses revealed a gradual increase in the proportion of older people with IS and a gradual increase in the proportion of younger people with hemorrhagic strokes. The cohort and period rate ratios varied by subtype, showing an increasing trend for IS and ICH but a decreasing trend for SAH. The stroke mortality attributable to high BMI increased significantly with age for IS and ICH, peaking between ages 50-70 for SAH. Notably, males had higher ASMR related to stroke but exhibited slighter declines or higher growth compared to females in China. Moreover, the population affected by fatal strokes tended to be older among females but more evenly distributed across a wider age range encompassing both younger and older individuals. CONCLUSION: The research findings indicate a rising trend in the ASMR of stroke and subtypes attributable to high BMI in China from 1990 to 2019, with different patterns of change for different subtypes, genders and ages. Consequently, it is imperative for public health authorities in China to formulate guidelines for specific stroke subtypes, genders and ages to prevent the burden of stroke attributable to high BMI.

Current non-invasive strategies for brain drug delivery: overcoming blood-brain barrier transport.

BACKGROUND: The blood-brain barrier (BBB) is a complex and dynamic structure that serves as a gatekeeper, restricting the migrations of most compounds and molecules from blood into the central nervous system (CNS). The BBB plays a crucial role in maintaining CNS physiological function and brain homeostasis. It can protect the CNS from the entrance of toxic and infectious agents, however, it also restricts the drug permeation into brain to play a therapeutic role. The BBB has been the biggest limiting hurdle to medications entering the brain excluding from the brain about 100% of large-molecule and more than 98% of all small-molecule neurotherapeutics. As a result, it is of inability for drug molecule to reach requisite concentrations within the brain. OBJECTIVE: With the aim of enhancing drug permeability and efficacy, a variety of strategies have been developed: invasive approaches, such as intraarterial delivery, intrathecal delivery, or administrating directly the drug intraventricularly and intracerebrally; non-invasive approaches that take advantage of innate BBB functions, using prodrugs, focused ultrasound, intranasal administration or nanotechnology. CONCLUSIONS: Here we mainly review recent developments and challenges related to non-invasive BBB-crossing techniques, whose benefits include higher efficacy, easier application, less treatment burden, better patient acceptability, and adherence. Additionally, we also analyze the potential of non-invasive methods in the treatment of CNS disorders and render them as a most suitable platform for the management of neurological diseases.

Analysis and projections of disease burden for different risk factors and sexes of ischemic stroke in young adults in China.

To estimate the rate of death, and disability-adjusted life years (DALYs) and project the disease burden of ischemic stroke due to relevant risk factors in young adults age 20-49 years by sex in China. Data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used. The age-standardized mortality (ASMR), age-standardized DALYs rate (ASDR), and estimated annual percentage changes (EAPC) were calculated to evaluate the temporal trends from 1990 to 2019. We also used the NORDPRED model to predict ASMR for ischemic stroke due to related risk factors in Chinese young adults over the next 10 years. From 1990 to 2019, the general age-standardized mortality [from 2.39 (1.97 to 2.99) in 1990 to 1.8 (1.41 to 2.18) in 2019, EAPC = - 1.23] and DALYs rates (from 171.7 (140.34 to 212.36) in 1990 to 144.4 (114.29 to 177.37) in 2019, EAPC = - 0.86) decreased for ischemic stroke in young adults in China. ASMR and ASDR decreased for all level 1 risk factors (including behavioral, environmental/occupational, and metabolic) from 1990 to 2019, with the slightest decrease for metabolic risks [ASMR from 1.86 (1.39 to 2.41) in 1990 to 1.53 (1.15 to 1.92) in 2019, ASDR from 133.68 (99.96 to 173.89) in 1990 to 123.54 (92.96 to 156.98) in 2019] and the largest decrease for environmental/occupational risks [ASMR from 1.57 (1.26 to 1.98) in 1990 to 1.03 (0.78 to 1.29) in 2019, ASDR from 110.91 (88.44 to 138.34) in 1990 to 80.03 (61.87 to 100.33) in 2019]. In general, high body-mass index, high red meat intake, and ambient particulate matter pollution contributed to the large increase in ASMR and ASDR between 1990 and 2019. Significant reductions in ASMR and ASDR were observed in low vegetables intake, household air pollution from solid fuels, lead exposure, and low fiber intake. In addition, there were sex differences in the ranking of ASMR attributable to risks in ischemic stroke. The disease burden of ischemic stroke attributable to relevant risk factors in young adults in China is greater and has a faster growth trend or a slower decline trend in males than in females (except for secondhand smoke). The apparent increasing trend of ASMR attributable to high fasting plasma glucose, high systolic blood pressure, high body-mass index, and high red meat intake was observed in males but not in females. The projected analysis showed an increasing trend in ASMR between 1990 and 2030 for all specific metabolic risks for males, but a decreasing trend for females. ASMR attributable to ambient particulate matter pollution showed an increasing trend from 1990 to 2030 for both males and females. The burden of ischemic stroke in young adults in China showed a downward trend from 1990 to 2019. Specific risk factors associated with the burden of ischemic stroke varied between the sexes. Corresponding measures need to be developed in China to reduce the disease burden of ischemic stroke among young adults.

Phospholipase D, a Novel Therapeutic Target Contributes to the Pathogenesis of Neurodegenerative and Neuroimmune Diseases.

Phospholipase D (PLD) is an enzyme that consists of six isoforms (PLD1-PLD6) and has been discovered in different organisms including bacteria, viruses, plants, and mammals. PLD is involved in regulating a wide range of nerve cells' physiological processes, such as cytoskeleton modulation, proliferation/growth, vesicle trafficking, morphogenesis, and development. Simultaneously, PLD, which also plays an essential role in the pathogenesis of neurodegenerative and neuroimmune diseases. In this review, family members, characterizations, structure, functions and related signaling pathways, and therapeutic values of PLD was summarized, then five representative diseases including Alzheimer disease (AD), Parkinson's disease (PD), etc. were selected as examples to tell the involvement of PLD in these neurological diseases. Notably, recent advances in the development of tools for studying PLD therapy envisaged novel therapeutic interventions. Furthermore, the limitations of PLD based therapy were also analyzed and discussed. The content of this review provided a thorough and reasonable basis for further studies to exploit the potential of PLD in the treatment of neurodegenerative and neuroimmune diseases.

Prediction of mechanical ventilation in Guillain-Barré syndrome at admission: Construction of a nomogram and comparison with the EGRIS model.

Background: Respiratory failure requiring mechanical ventilation (MV) is a common and severe complication of Guillain-Barré syndrome (GBS) with a reported incidence ranging from 20 % to 30 %. Thus, we aim to develop a nomogram to evaluate the risk of MV in patients with GBS at admission and tailor individualized care and treatment. Methods: A total of 633 patients with GBS (434 in the training set, and 199 in the validation set) admitted to the First Hospital of Jilin University, Changchun, China from January 2010 to January 2021 were retrospectively enrolled. Subjects (n = 71) from the same institution from January 2021 to May 2022 were prospectively collected and allocated to the testing set. Multivariable logistic regression analysis was applied to build a predictive model incorporating the optimal features selected in the least absolute shrinkage and selection operator (LASSO) in the training set. The predictive model was validated using internal bootstrap resampling, an external validation set, and a prospective testing set, and the model's performance was assessed by using the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Finally, we established a multivariable logistic model by using variables of the Erasmus GBS Respiratory Insufficiency Score (EGRIS) and did the same analysis to compare the performance of our predictive model with the EGRIS model. Results: Variables in the final model selected by LASSO included time from onset to admission, facial and/or bulbar weakness, Medical Research Council sum score at admission, neutrophil-to-lymphocyte ratio, and platelet-lymphocyte ratio. The model presented as a nomogram displaying favorable discriminative ability with a C-index of 0.914 in the training set, 0.903 in the internal validation set, 0.953 in the external validation set, and 0.929 in the testing set. The model was well-calibrated and clinically useful as assessed by the calibration curve and DCA. As compared with the EGRIS model, our predictive model displayed satisfactory performance. Conclusions: We constructed a nomogram for early prediction of the risk of MV in patients with GBS. This model had satisfactory performance and appeared more efficient than the EGRIS model in Chinese patients with GBS.

Prediction of clinical progression in nervous system diseases: plasma glial fibrillary acidic protein (GFAP).

Glial fibrillary acidic protein (GFAP), an intracellular type III intermediate filament protein, provides structural support and maintains the mechanical integrity of astrocytes. It is predominantly found in the astrocytes which are the most abundant subtypes of glial cells in the brain and spinal cord. As a marker protein of astrocytes, GFAP may exert a variety of physiological effects in neurological diseases. For example, previous published literatures showed that autoimmune GFAP astrocytopathy is an inflammatory disease of the central nervous system (CNS). Moreover, the studies of GFAP in brain tumors mainly focus on the predictive value of tumor volume. Furthermore, using biomarkers in the early setting will lead to a simplified and standardized way to estimate the poor outcome in traumatic brain injury (TBI) and ischemic stroke. Recently, observational studies revealed that cerebrospinal fluid (CSF) GFAP, as a valuable potential diagnostic biomarker for neurosyphilis, had a sensitivity of 76.60% and specificity of 85.56%. The reason plasma GFAP could serve as a promising biomarker for diagnosis and prediction of Alzheimer's disease (AD) is that it effectively distinguished AD dementia from multiple neurodegenerative diseases and predicted the individual risk of AD progression. In addition, GFAP can be helpful in differentiating relapsing-remitting multiple sclerosis (RRMS) versus progressive MS (PMS). This review article aims to provide an overview of GFAP in the prediction of clinical progression in neuroinflammation, brain tumors, TBI, ischemic stroke, genetic disorders, neurodegeneration and other diseases in the CNS and to explore the potential therapeutic methods.

Gut flora in multiple sclerosis: implications for pathogenesis and treatment.

ABSTRACT: Multiple sclerosis is an inflammatory disorder characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Although current first-line therapies can help manage symptoms and slow down disease progression, there is no cure for multiple sclerosis. The gut-brain axis refers to complex communications between the gut flora and the immune, nervous, and endocrine systems, which bridges the functions of the gut and the brain. Disruptions in the gut flora, termed dysbiosis, can lead to systemic inflammation, leaky gut syndrome, and increased susceptibility to infections. The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors, and gut flora may play a pivotal role in regulating immune responses related to multiple sclerosis. To develop more effective therapies for multiple sclerosis, we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis. This review provides an overview of the role of the gut flora in multiple sclerosis.

Distribution characteristics of antinuclear antibodies in Guillain-Barré syndrome and its relationship with disease severity.

BACKGROUND: Guillain-Barré syndrome (GBS), an acquired immune-mediated autoimmune disorder affecting the peripheral nervous system (PNS), is associated with autoimmunity. The presence of autoantibodies in the blood is an important feature of autoimmune diseases. Herein, we explored the distribution characteristics of the antinuclear antibodies (ANAs) in GBS and the correlation between ANAs and disease severity. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of 170 GBS patients. According to ANAs, GBS patients were divided into ANAs positive and negative groups. The clinical characteristics of these two groups were compared. The distribution difference was also compared between male and female GBS patients. In addition, all enrolled patients were divided into more severe group and milder group according to whether the Hughes score at nadir ≥ 3 or not. Gender, age, and ANAs were compared between the two groups. RESULTS: In this study, the positive rate of ANAs was 27.1 % in 170 GBS patients, among which anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 made up the largest proportion. In the ANAs positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, and higher level of CSF IgG than the ANAs negative group. Compared to the ANAs negative group, Medical Research Council (MRC) scores on admission and at nadir were lower, and Hughes functional Grading Scale (HFGS) scores on admission and at nadir were higher in GBS patients with ANAs positive group. Erasmus GBS Respiratory Insufficiency Score (EGRIS) in ANAs positive GBS patients group was significantly higher than ANAs negative group. Gender had no effects on the distribution of ANAs in GBS patients. Moreover, we found that the anti-SSA-60 antibodies and age were positively correlated with GBS severity. In addition, in the anti-SSA-60 antibody positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, higher HFGS scores on admission/at nadir, and lower MRC scores at nadir compared with the anti-SSA-60 antibody negative group. CONCLUSION: Anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 were the most common ANAs in GBS patients. Anti-SSA-60 antibodies and age positively correlated with GBS severity. Positive anti-SSA-60 antibodies and age were independent predictors of GBS patient severity.

Associations of Serum Liver Function with Cerebral Blood Flow in Patients with Alzheimer's Disease.

Background: Increasing evidence suggests that both amyloid-ß metabolism disorders in the liver and cerebral hypoperfusion play an important role in the pathogenesis of Alzheimer's disease (AD). However, the relevance of liver function alterations to cerebral blood flow (CBF) of patients with AD remains unclear. Objective: We aimed to investigate the associations between liver function changes and CBF of patients with AD. Methods: We recruited 17 patients with sporadic AD. In addition to physical and neurological examinations, detection of AD biomarkers in cerebrospinal fluid by enzyme-linked immunosorbent assay and CBF assessment by arterial spin labeling sequence of magnetic resonance image scans as well as measure of liver function markers in serum by routine laboratory testing were conducted. Neuropsychological tests were evaluated, including Mini-Mental State Examination and Montreal Cognitive Assessment. Linear and rank correlations were performed to test the associations of liver function alterations with regional CBF of AD. Results: We found that liver function markers, especially total protein, the ratio of albumin to globin, globin, alkaline phosphatase, and aspartate aminotransferase were significantly associated with regional CBF of AD patients. Conclusions: These findings demonstrated significant associations between perfusion in certain brain regions of AD and alterations of liver function markers, particularly proteins and liver enzymes, which might provide implications to the pathogenesis and treatment of AD.

Associations of apolipoprotein E ε4 allele, regional cerebral blood flow, and serum liver function markers in patients with cognitive impairment.

Introduction: The ε4 allele of the apolipoprotein E gene (APOE4) is expressed abundantly in both the brain and peripheral circulation as a genetic risk factor for Alzheimer's disease (AD). Cerebral blood flow (CBF) dysfunction is an essential feature of AD, and the liver plays an important role in the pathogenesis of dementia. However, the associations of APOE4 with CBF and liver function markers in patients with cognitive impairment remains unclear. We aimed to evaluate the associations of APOE4 with CBF measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI) and serum liver function markers in participants who were diagnosed with cognitive impairment. Methods: Fourteen participants with AD and sixteen with amnestic mild cognitive impairment (MCI) were recruited. In addition to providing comprehensive clinical information, all patients underwent laboratory tests and MRI. All participants were divided into carriers and noncarriers of the ε4 allele, and T-tests and Mann-Whitney U tests were used to observe the differences between APOE4 carriers and noncarriers in CBF and liver function markers. Results: Regarding regional cerebral blood flow (rCBF), APOE4 carriers showed hyperperfusion in the bilateral occipital cortex, bilateral thalamus, and left precuneus and hypoperfusion in the right lateral temporal cortex when compared with noncarriers. Regarding serum liver function markers, bilirubin levels (including total, direct, and indirect) were lower in APOE4 carriers than in noncarriers. Conclusion: APOE4 exerts a strong effect on CBF dysfunction by inheritance, representing a risk factor for AD. APOE4 may be related to bilirubin metabolism, potentially providing specific neural targets for the diagnosis and treatment of AD.