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Abstract Background Cerebral venous sinus thrombosis (CVST) is a rare but potentially life-threatening subtype of stroke. Prompt and appropriate anticoagulation is crucial for improving the prognosis of CVST and preventing its recurrence. Identifying the underlying cause of CVST is decisive for guiding anticoagulant selection and determining treatment duration. Case Presentation A 50-year-old man presented with a 35-day history of headache, nausea, vomiting, and blurred vision. Digital subtraction angiography performed at another facility revealed CVST. A contrast-enhanced black-blood MRI at our center confirmed the diagnosis, which was supported by a high intracranial pressure of 330mmH2O. Laboratory tests showed elevated leukocytes and platelet counts, raising suspicion of an underlying myeloproliferative neoplasms (MPNs). A bone marrow biopsy demonstrated increased megakaryocytes and granulocytes, and genetic testing identified the presence of the Janus kinase 2 V617F (JAK2 V617F) mutation, leading to a diagnosis of pre-primary myelofibrosis (pre-PMF). During hospitalization, anticoagulation with nadroparin calcium and fibrinolytic therapy were initiated. Upon discharge, rivaroxaban and aspirin were prescribed to prevent CVST recurrence and arterial thrombosis. Conclusion This case highlights the importance of recognizing dynamic changes in routine blood tests that may link CVST to underlying hematological disorders. The JAK2 mutation is not only associated with MPNs but also increases the risk of thrombosis, including CVST. Further investigation is warranted to better understand the mechanisms by which JAK2 mutations contribute to thrombosis and to explore the potential benefits of JAK2 inhibitors in reducing this risk.

Cyclin D1 has been recognized as an oncogene due to its abnormal upregulation in different types of cancers. Here, we demonstrated that cyclin D1 is SUMOylated, and we identified Itch as a specific E3 ligase recognizing SUMOylated cyclin D1 and mediating SUMO-induced ubiquitination and proteasome degradation of cyclin D1. We generated cyclin D1 mutant mice with mutations in the SUMOylation site, phosphorylation site, or both sites of cyclin D1, and found that double mutant mice developed a Mantle cell lymphoma (MCL)-like phenotype. We showed that arsenic trioxide (ATO) enhances cyclin D1 SUMOylation-mediated degradation through inhibition of cyclin D1 deSUMOylation enzymes, leading to MCL cell apoptosis. Treatment of severe combined immunodeficiency (SCID) mice grafted with MCL cells with ATO resulted in a significant reduction in tumor growth. In this study, we provide novel insights into the mechanisms of MCL tumor development and cyclin D1 regulation and discover a new strategy for MCL treatment.

INTRODUCTION: Antithrombotic therapy prevents adverse ischemic events following acute ischemic stroke (AIS). Intravenous tirofiban provides desirable antiplatelet effects, especially in patients who are vulnerable to neurological deterioration (ND). AIM: The aim of the study was to test the hypothesis that intravenous administration of tirofiban, initiated within 24 h of ictus and continued for consecutive 72 h, would be more effective than aspirin in reducing the risk of ND within 72 h of enrollment among patients with potentially atherothrombotic ischemic stroke. METHODS: The Safety and Efficacy of Tirofiban in Preventing Neurological Deterioration in Acute Ischemic Stroke (TREND) trial is an investigator-initiated, multicenter, prospective, randomized, open-label, masked endpoint study. Its eligibility criteria included AIS secondary to potential atherosclerosis, a National Institutes of Health Stroke Scale (NIHSS) score ranging from 4 to 20 points, ineligibility for recanalization therapy, and administration within 24 h postsymptom onset. Randomization was performed at a 1:1 ratio to allocate 420 patients into two groups to receive an intravenous tirofiban bridge to oral antiplatelet drugs or direct oral antiplatelet drugs. OUTCOMES: The primary outcome is the proportion of patients with a ≥4-point increase in NIHSS score within 72 h of intervention compared to the score at enrollment. The key secondary outcomes include changes in NIHSS score, modified Rankin scale (mRS) score at 90 days, and dichotomized mRS scores (0–2 vs. 3–6 and 0–1 vs. 2–6) at 90 days. The safety variables are symptomatic intracerebral hemorrhage, any intracerebral hemorrhage, and systemic hemorrhage within 72 h after randomization and 90-day mortality. CONCLUSIONS: The TREND trial may identify the suitability of intravenous tirofiban as a routine clinical strategy to prevent ND in patients with AIS within 24 h of the onset of symptoms. TRIAL REGISTRATION: http://www.clinicaltrials.gov (identifier: NCT04491695).

Introduction: Stroke is characterized by high incidence, recurrence rate, and mortality. Patients with acute ischemic stroke (AIS) who are ineligible for acute revascularization therapy require more effective medication treatments. A previous clinical study showed that Ruyi Zhenbao tablets and Baimai ointments might be effective against AIS; however, high-quality clinical evidence supporting their application in AIS is lacking. To explore the efficacy of the two classic Tibetan medicines in the treatment of AIS, a randomized clinical trial will be conducted in patients with AIS who are not eligible for thrombolytic treatment. Methods: A prospective, randomized, multiple-center, double-blinded, placebo-controlled, and parallel-group trial will be conducted. We shall randomize 480 eligible participants to either the intervention or the control group. The distribution ratio of each group will be 1:1:1:1, including 120 patients each in the dual-medication group, the Baimai ointment group, the Ruyi Zhenbao tablet group, and the placebo group. Participants will be treated with medication for 8 weeks, and they will receive three follow-up visits: at 4 weeks (D29), 8 weeks (D56), and 90 days (D90) after commencing treatment. The primary outcome will be D90 change in the simplified Fugl-Meyer score from baseline to posttreatment. The secondary outcomes are as follows: D29 change of simplified Fugl-Meyer score from baseline to posttreatment; proportion of participants whose D29 NIHSS scores decreased by four or more points from baseline D90 proportion of subjects with mRS score of 0–2 (inclusive); D90 proportion of subjects with Barthel index score ≥95; D90 incidence of cardiovascular and cerebrovascular events. Safety endpoint includes mortality within 90 days; proportion of subjects with adverse events/serious adverse events within 90 days. Conclusion: This research protocol lays a solid groundwork for its practical execution. This study is poised to serve as a reference for other Tibetan medicine researchers, contributing to the reduction of stroke-related expenditures globally and, in turn, benefiting a broader population of stroke patients.

Objective: This study aimed to explore the impact of late night shift work on the functional outcomes of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT). Methods: Consecutive AIS patients who underwent EVT between June 2019 and June 2021 were enrolled and divided into non-night shift work and night shift work groups based on their occupational histories. The primary outcome was the modified Rankin Scale score defined 3-month functional outcome. The secondary outcomes were 3-month mortality, symptomatic intracerebral hemorrhage (sICH), ICH and early recanalization. Results: A total of 285 patients were enrolled, 35 patients (12.3%) were night shift workers, who were younger (P

Abstract The coronavirus disease 2019 (COVID-19) pandemic has caused an unprecedented disruption to health care systems around the globe. Stroke is still an ongoing issue during the pandemic. We investigated the impact of the COVID-19 outbreak on emergent stroke care in Beijing, China. This is a retrospective analysis of two groups of patients with acute ischaemic stroke (AIS) registered in the Beijing Emergency Care Database between January 1, 2019, and December 31, 2020. Based on a database including 77 stroke centres, the quantity and quality of emergency care for stroke were compared. Subgroup analyses based on hospitals in different areas (high-risk and low/medium-risk areas) were carried out. A total of 6440 and 8699 admissions with suspected stroke were recorded in 2020 and 2019, respectively. There were no significant differences in the mean age and sex distribution for the patients between the two observational periods. The number of AIS admissions decreased by approximately 23.9% during the COVID-19 pandemic compared to that during the prepandemic period. The proportions of intravenous thrombolysis and endovascular treatment were 76.4% and 13.1%, respectively, in 2020, which were higher than those in 2019 (71.7% and 9.3%, respectively). There was no statistically significant difference in the time from stroke onset to arrival at the hospital (97.97 ± 23.09 min vs. 99.40 ± 20.76 min, p = 0.832) between the two periods. The door-to-needle time for thrombolysis (44.92 ± 9.20 min vs. 42.37 ± 9.06 min, p

Idiopathic internal carotid artery (ICA) vasospasm is a rare cause of ischemic stroke. Its pathophysiology remains unclear and diagnostic and treatment protocols are yet to be defined. A 45-year-old male, presenting with recurrent transient dizziness, blurred vision, and speech disturbances, was diagnosed with recurrent ischemic stroke caused by bilateral ICA and middle cerebral artery (MCA) vasospasm, and the vascular ultrasound and imaging techniques have grabbed the reversible changes in a short time. This case underscores the importance of considering idiopathic ICA vasospasm as a potential cause of recurrent ischemic stroke, even in the absence of common diagnostic markers. The case also indicates the possible, albeit rare, involvement of the MCA in this condition. Therefore, it is crucial to maintain a high index of suspicion for idiopathic ICA vasospasm in similar clinical presentations and to explore more inclusive diagnostic criteria.

The field of spatial cognitive training and evaluation has rapidly evolved. However, the low learning motivation and engagement of the subjects hinder the widespread use of spatial cognitive training. This study designed a home-based spatial cognitive training and evaluation system (SCTES), which aimed to train subjects on spatial cognitive tasks for 20 days, and compared the brain activities before and after the training. This study also evaluated the feasibility of using a portable all-in-one prototype for cognitive training that combined a virtual reality (VR) head-mounted display with high-quality electroencephalogram (EEG) recording. During the course of training, the length of the navigation path and the distance between the starting position and the platform position revealed significant behavioral differences. In the testing sessions, the subjects showed significant behavioral differences in the time it took to complete the test task before and after training. After only four days of training, the subjects demonstrated significant differences in the Granger causality analysis (GCA) characteristics of brain regions in the ${\delta }$ , ${\theta }$ , ${\alpha }_{{{1}}}$ , ${\beta }_{{{2}}}$ , and ${\gamma }$ frequency bands of the EEG, as well as significant differences in the GCA of the EEG in the ${\beta }_{{{1}}}$ , ${\beta }_{{{2}}}$ , and ${\gamma }$ frequency bands between the two test sessions. The proposed SCTES used a compact and all-in-one form factor to train and evaluate spatial cognition and collect EEG signals and behavioral data simultaneously. The recorded EEG data can be used to quantitatively assess the efficacy of spatial training in patients with spatial cognitive impairments.

In order to improve the traditional common space pattern (CSP) algorithm pattern in EEG feature extraction, this study proposes a feature extraction method of EEG signals based on permutation conditional mutual information common space pattern (PCMICSP), which used the sum of the permutation condition mutual information matrices of each lead to replacing the mixed spatial covariance matrix in the traditional CSP algorithm, and its eigenvectors and eigenvalues are used to construct a new spatial filter. Then the spatial features in the different time domains and frequency domains are combined to construct the two-dimensional pixel map, Finally, a convolutional neural network (CNN) is used for binary classification. The EEG signals of 7 community elderly before and after spatial cognitive training in virtual reality (VR) scenes were used as the test data set. The average classification accuracy of the PCMICSP algorithm for pre-test and post-test EEG signals is 98%, which was higher than that of CSP based on CMI (conditional mutual information), CSP based on MI (mutual information), and traditional CSP in the combination of four frequency bands. Compared with the traditional CSP method, PCMICSP can be used as a more effective method to extract the spatial features of EEG signals. Therefore, this paper provides a new approach to solving the strict linear hypothesis of CSP and can be used as a valuable biomarker for the spatial cognitive evaluation of the elderly in the community.

BackgroundIschemic stroke (IS) is one of the most common serious secondary diseases of atrial fibrillation (AF) within 1 year after its occurrence, both of which have manifestations of ischemia and hypoxia of the small vessels in the early phase of the condition. The fundus is a collection of capillaries, while the retina responds differently to light of different wavelengths. Predicting the risk of IS occurring secondary to AF, based on subtle differences in fundus images of different wavelengths, is yet to be explored. This study was conducted to predict the risk of IS occurring secondary to AF based on multi-spectrum fundus images using deep learning.MethodsA total of 150 AF participants without suffering from IS within 1 year after discharge and 100 IS participants with persistent arrhythmia symptoms or a history of AF diagnosis in the last year (defined as patients who would develop IS within 1 year after AF, based on fundus pathological manifestations generally prior to symptoms of the brain) were recruited. Fundus images at 548, 605, and 810 nm wavelengths were collected. Three classical deep neural network (DNN) models (Inception V3, ResNet50, SE50) were trained. Sociodemographic and selected routine clinical data were obtained.ResultsThe accuracy of all DNNs with the single-spectral or multi-spectral combination images at the three wavelengths as input reached above 78%. The IS detection performance of DNNs with 605 nm spectral images as input was relatively more stable than with the other wavelengths. The multi-spectral combination models acquired a higher area under the curve (AUC) scores than the single-spectral models.ConclusionsThe probability of IS secondary to AF could be predicted based on multi-spectrum fundus images using deep learning, and combinations of multi-spectrum images improved the performance of DNNs. Acquiring different spectral fundus images is advantageous for the early prevention of cardiovascular and cerebrovascular diseases. The method in this study is a beneficial preliminary and initiative exploration for diseases that are difficult to predict the onset time such as IS.

In this study, a multi-scale high-density convolutional neural network (MHCNN) classification method for spatial cognitive ability assessment was proposed, aiming at achieving the binary classification of task-state EEG signals before and after spatial cognitive training. Besides, the multi-dimensional conditional mutual information method was used to extract the frequency band features of the EEG data. And the coupling features under the combination of multi-frequency bands were transformed into multi-spectral images. At the same time, the idea of Densenet was introduced to improve the multi-scale convolutional neural network. Firstly, according to the discreteness of multispectral EEG image features, two-scale convolution kernels were used to calculate and learn useful channel and frequency band feature information in multispectral image data. Secondly, to enhance feature propagation and reduce the number of parameters, the dense network was connected after the multi-scale convolutional network, and the learning rate change function of the stochastic gradient descent algorithm was optimized to objectively evaluate the training effect. The experimental results showed that compared with the classical convolution neural network (CNN) and multi-scale convolution neural network, the proposed MHCNN had better classification performance in the six frequency band combinations with the highest accuracy of 98%: Theta-Alpha2-Gamma, Alpha2-Beta2-Gamma, Beta1-Beta2-Gamma, Theta-Beta2-Gamma, Theta- Alpha1-Gamma, and Alpha1-Alpha2-Gamma. By comparing the classification results of six frequency band combinations, it was found that the combination of the Theta-Beta2-Gamma band had the best classification effect. The MHCNN classification method proposed in this research could be used as an effective biological indicator of spatial cognitive training effect and could be extended to other brain function evaluations.

ObjectiveSerum inflammatory biomarkers play crucial roles in the development of acute ischemic stroke (AIS). In this study, we explored the association between inflammatory biomarkers including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR), and clinical outcomes in AIS patients who achieved successful recanalization.MethodsPatients with AIS who underwent endovascular thrombectomy (EVT) and achieved a modified thrombolysis in the cerebral infarction scale of 2b or 3 were screened from a prospective cohort at our institution between January 2013 and June 2021. Data on blood parameters and other baseline characteristics were collected. The functional outcome was an unfavorable outcome defined by a modified Rankin Scale of 3–6 at the 3-month follow up. Other clinical outcomes included symptomatic intracranial hemorrhage (sICH) and 3-month mortality. Multivariable logistic regression analysis was performed to evaluate the effects of PLR, NLR, and MLR on clinical outcomes.ResultsA total of 796 patients were enrolled, of which 89 (11.2%) developed sICH, 465 (58.4%) had unfavorable outcomes at 3 months, and 168 (12.1%) died at the 3-month follow up. After adjusting for confounding variables, a higher NLR (OR, 1.076; 95% confidence interval [CI], 1.037–1.117; p < 0.001) and PLR (OR, 1.001; 95%CI, 1.000–1.003; p = 0.045) were significantly associated with unfavorable outcomes, the area under the receiver operating characteristic curve of NLR and PLR was 0.622 and 0.564, respectively. However, NLR, PLR, and MLR were not independently associated with sICH and 3-month mortality (all adjusted p > 0.05).ConclusionOverall, our results indicate that higher PLR and NLR were independently associated with unfavorable functional outcomes in AIS patients with successful recanalization after EVT; however, the underlying mechanisms are yet to be elucidated.

ObjectiveThis study aimed to develop and validate a nomogram to predict malignant cerebral artery infarction (MMI) after endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) in the modern thrombectomy era.MethodsWe retrospectively analyzed data from a prospective cohort of consecutive patients with AIS who underwent EVT at Xuanwu hospital between January 2013 and June 2021. A multivariable logistic regression model was employed to construct the nomogram for predicting MMI after EVT. The discrimination and calibration of the nomogram were assessed both in the derivation and validation cohorts.ResultsA total of 605 patients were enrolled in this study, with 425 in the derivation cohort and 180 in the validation cohort. The nomogram was developed based on admission systolic blood pressure (SBP), the National Institute of Health Stroke Score (NIHSS), the Alberta Stroke Program Early Computed Tomography Score (ASPECTS), vessel occlusion site, EVT time window, and recanalization status. The nomogram displayed good discrimination with the area under the receiver operating characteristics (ROCs) curve (AUC) of 0.783 [95% confidence interval (CI), 0.726–0.840] in the derivation cohort and 0.806 (95% CI, 0.738–0.874) in the validation cohort. The calibration of the nomogram was good as well, with the Hosmer–Lemeshow test of p = 0.857 in the derivation cohort and p = 0.275 in the validation cohort.ConclusionIn the modern thrombectomy era, a nomogram containing admission SBP, NIHSS, ASPECTS, vessel occlusion site, EVT time window, and recanalization status may predict the risk of MMI after EVT in patients with AIS.

BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory factor in the pathogenesis of atherosclerotic plaque and is associated with an increased risk of ischemic stroke. Whether Lp-PLA2 is associated with stenosis subtypes in acute ischemic stroke (AIS) has not been investigated.MethodsA total of 126 eligible AIS patients were divided into four groups: (1) no cerebral artery stenosis (NCS); (2) intracranial artery stenosis (ICAS); (3) extracranial artery stenosis (ECAS); and (4) combined intracranial and extracranial artery stenosis (IECS). Associations between serum Lp-PLA2 levels and the stenosis subtypes were assessed.ResultsThe ICAS group had a lower frequency of dyslipidemia as compared to the NCS group and the IECS group (35.3% vs. 70% vs. 71.8%, respectively, p = 0.001) and was more likely to be symptomatic than the ECAS group (76.5% vs. 43.8%, respectively, p = 0.014). Lp-PLA2 levels in the ICAS group were 112.2 ± 66.8 μg/L which are, higher than those in the NCS, ECAS, and IECS groups (81.7 ± 38.5, 106.1 ± 57.8, 89.3 ± 52.2 μg/L, respectively, p = 0.025). In the third and fourth quartiles of Lp-PLA2 levels, stenosis had occurred more frequently in the ICAS group than in the other three groups (third Q: 50.0% vs. 3.1% vs. 28.1% vs. 18.8%, p = 0.002; fourth Q: 48.4% vs. 16.1% vs. 25.8% vs. 9.7%, p = 0.014). Lp-PLA2 levels were higher in patients with more or severe stenosis in the ICAS group.ConclusionsElevated Lp-PLA2 levels were differentially associated with increased risk in AIS patients with ICAS compared to those with ECAS or no stenosis. Lp-PLA2 may be a promising biomarker and potential therapeutic target for ICAS.

ObjectivesTo explore the alterations in immune cell composition in peripheral blood in patients with acute ischemic stroke (AIS) based on their age group.MethodsPatients with imaging confirmed AIS were enrolled from April 2019 to January 2020 and were divided into three groups according to their ages: 65 years (group-C). Blood samples were collected immediately when the patients were admitted to our ward prior to any intervention. Flow cytometry was used to analyze immune cell composition in peripheral blood.ResultsA total of 41 eligible patients were included for final analysis. Among the three groups, the proportions of CD56+ CD16dim NK cells were least to greatest in group-B, group-A, then group-C, respectively. With increasing age, there was a decrease in the proportion of CD3+ T-cells (group-A vs. group-C, P = 0.016) and CD3+CD4+ T-cells (group-C vs. group-A, P = 0.008; group-C vs. group-B P = 0.026). Meanwhile, no significant differences in proportions of monocytes and B cells were observed.ConclusionsThe compositions of immune cells in peripheral blood of AIS patients were distinct when divided by age groups. Differences in immune cell ratios may affect clinical outcomes and foreshadows possible need for customized treatment of AIS in different age groups.

While several large pivotal clinical trials recently revealed a substantial benefit of endovascular thrombectomy for acute ischemic stroke (AIS) caused by large-vessel occlusion, many patients still experience mediocre prognosis. Enlargement of the ischemic core, failed revascularization, incomplete reperfusion, distal embolization, and secondary reperfusion injury substantially impact the salvaging of brain tissue and the functional outcomes of AIS. Here, we propose novel concept of “Multiphase Adjuvant Neuroprotection” as a new paradigm that may help guide our search for adjunctive treatments to be used together with thrombectomy. The premise of multiphase adjuvant neuroprotection is based on the diverse and potentially nonoverlapping pathophysiologic mechanisms that are triggered before, during, and after thrombectomy therapies. Before thrombectomy, strategies should focus on preventing the growth of the ischemic core; during thrombectomy, improving recanalization while reducing distal embolization and maximizing reperfusion are of significant importance; after reperfusion, strategies should focus on seeking targets to reduce secondary reperfusion injury. The concept of multiphase adjuvant neuroprotection, wherein different strategies are employed throughout the various phases of clinical care, might provide a paradigm to minimize the final infarct size and improve functional outcome in AIS patients treated with thrombectomy. With the success of thrombectomy in selected AIS patients, there is now an opportunity to revisit stroke neuroprotection. Notably, if the underlying mechanisms of these neuroprotective strategies are identified, their role in the distinct phases will provide further avenues to improve patient outcomes of AIS.

BackgroundDespite the continuing effort in investigating the preventive therapies for stroke-associated pneumonia (SAP), which is closely associated with unfavorable outcomes, conclusively effective therapy for the prevention of SAP is still lacking. Remote ischemic conditioning (RIC) has been proven to improve the survival in the sepsis model and inflammatory responses have been indicated as important mechanisms involved in the multi-organ protection effect of RIC. This study aimed to assess the safety and the preliminary efficacy of RIC in the prevention of SAP in patients with acute ischemic stroke.MethodsWe performed a proof-of-concept, pilot open-label randomized controlled trial. Eligible patients (age > 18 years) within 48 h after stroke onset between March 2019 and October 2019 with acute ischemic stroke were randomly allocated (1:1) to the RIC group and the control group. All participants received standard medical therapy. Patients in the RIC group underwent RIC twice daily for 6 consecutive days. The safety outcome included any adverse events associated with RIC procedures. The efficacy outcome included the incidence of SAP, changes of immunological profiles including mHLA-DR, TLR-2, and TLR-4 as well as other plasma parameters from routine blood tests.ResultsIn total, 46 patients aged 63.1 ± 12.5 years, were recruited (23 in each group). Overall, 19 patients in the RIC group and 22 patients in the control group completed this study. No severe adverse event was attributed to RIC procedures. The incidence of SAP was lower in the remote ischemic conditioning group (2 patients [10.5%]) than that in the control group (6 patients [27.3%]), but no significant difference was detected in both univariate and multivariate analysis (p = 0.249 and adjusted p = 0.666). No significance has been found in this pilot trial in the level of immunological profiles HLA-DR, TLR4 and TLR2 expressed on monocytes as well as blood parameters tested through routine blood tests between the two groups (p > 0.05). The IL-6 and IL-1β levels at day 5 after admission in the RIC group were lower than those in the control group (p < 0.05).InterpretationThis proof-of-concept pilot randomized controlled trial was to investigate RIC as a prevention method for SAP. Remote ischemic conditioning is safe in the prevention of SAP in patients with acute ischemic stroke. The preventive effect of RIC on SAP should be further validated in future studies.

BackgroundSymptomatic intracranial hemorrhage (sICH) is a devastating complication of endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) and is associated with high risk of disability and mortality. This study intended to evaluate the predictors of sICH after EVT in patients with large vessel occlusion (LVO)-induced AIS.MethodsWe conducted a retrospective review on consecutive AIS patients who underwent EVT in our University hospital between January 2019 and August 2020. The patients were classified into two groups based upon the occurrence of sICH. The main outcomes were the occurrence of sICH using the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristics (ROC) curves were used to identify independent predictors of sICH after EVT.ResultsThree hundred and 69 patients were enrolled in the study, of which 16.8% (n = 62) developed sICH. Favorable neurological outcome was lower in patients with sICH than in patients without sICH (6.5 vs. 43.3%; P < 0.001), with the overall mortality being 112 (30.4%) at 90 days post- EVT. Results from univariate analysis showed significant differences between the two groups in the prevalence of diabetes, initial Alberta Stroke Program Early CT Score (ASPECTS) score, National Institutes of Health Stroke Scale (NIHSS) score after operation, the levels of fasting blood glucose (FBG), neutrophil to lymphocyte ratio (NLR), platelets (PLT), and thrombin time (TT) at admission. Multivariate logistic regression analysis showed that FBG ≥ 7.54 mmol/L (OR: 2.765; 95% confidence interval [CI]: 1.513–5.054), NLR ≥ 5.48 (OR: 2.711; 95% CI: 1.433–5.128), TT at admission ≥ 16.25 s (OR: 2.022; 95% CI: 1.115–3.667), and NIHSS score within 24 h after the operation ≥ 10 (OR: 3.728; 95% CI: 1.516–9.170) were independent predictors of sICH. The combination of NLR ≥ 5.48, FBG ≥ 7.54 mmol/L, TT at admission ≥ 16.25 s, and NIHSS score within 24 h after the operation ≥ 10 generated an optimal prediction model (AUC: 0.723).ConclusionHigher levels of FDG, NLR, TT at admission, and NIHSS score after operation were associated with sICH after EVT in patients with LVO-induced AIS.

Background: Secondary stroke prevention after a high-risk, non-disabling ischemic cerebrovascular event needs to be enhanced. The study was conducted to investigate whether remote ischemic conditioning (RIC) is effective in preventing recurrent ischemic events within 3 months.Methods: This was a four-center, single-arm, open-label Phase IIa futility trial (PICNIC-One Study). Adult patients (≥18 years of age) who had an acute minor ischemic stroke (AMIS) with a National Institutes of Health Stroke Scale score ≤ 3 or a transient ischemic attack (TIA) with moderate-to-high risk of stroke recurrence (ABCD score ≥ 4) within 14 days of symptom onset were recruited. Patients received RIC as adjunctive therapy to routine secondary stroke prevention regimen. RIC consisted of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs (45 min) on bilateral upper limbs twice a day for 90 days.Results: A total of 285 patients met the study criteria, of which 167 provided signed informed consent and were enrolled. Data from 162 were analyzed with five subjects excluded. Recurrent AIS/TIA occurred in 6/162 (3.7%) patients within 3 months, with no occurrence of hemorrhagic stroke. The top three adverse events were upper limb pain (44/162, 27.2%), petechia (26/162, 16.0%), and heart palpitation (5/162, 3.1%). About 68 (42.0%) subjects completed ≥ 50% of 45-min RIC sessions.Conclusions: RIC is a safe add-on procedure and it has a potential benefit in reducing recurrent cerebrovascular events in patients with high-risk, non-disabling ischemic cerebrovascular events as the risk of stroke/TIA events is lower than expected; however, its compliance needs to be improved. Our study provides critical preliminary data to plan a large sample size, randomized controlled clinical study to systematically investigate the safety and efficacy of RIC in this population.

Land surface temperature (LST) is an important parameter in determining surface energy balance and a fundamental variable detected by the advanced geostationary radiation imager (AGRI), the main payload of FY-4A. FY-4A is the first of a new generation of Chinese geostationary satellites, and the detection product of the satellite has not been extensively validated. Therefore, it is important to conduct a comprehensive assessment of this product. In this study, the performance of the FY-4A LST product in the Hunan Province was authenticity tested with in situ measurements, triple collocation analyzed with reanalysis products, and impact analyzed with environmental factors. The results confirm that FY-4A captures LST well (R = 0.893, Rho = 0.915), but there is a general underestimation (Bias = −0.6295 °C) and relatively high random error (RMSE = 8.588 °C, ubRMSE = 5.842 °C). In terms of accuracy, FY-4A LST is more accurate for central-eastern, northern, and south-central Hunan Province and less accurate for western and southern mountainous areas and Dongting Lake. FY-4A LST is not as accurate as Himawari-8 LST; its accuracy also varies seasonally and between day and night. The accuracy of FY-4A LST decreases as elevation, in situ measured LST, surface heterogeneity, topographic relief, slope, or NDVI increase and as soil moisture decreases. FY-4A LST is also more accurate when the land cover is cultivated land or artificial surfaces or when the landform is a platform for other land covers and landforms. The conclusions drawn from the comprehensive analysis of the large quantity of data are generalizable and provide a quantitative baseline for assessing the detection capability of the FY-4A satellite, a reference for determining improvement in the retrieval algorithm, and a foundation for the development and application of future domestic satellite products.

The investigation for etiology of ischemic stroke in young adults remains a diagnostic challenge. Hyoid bone–related carotid injury is a rare and under-recognized cause of ischemic stroke, without established guidelines. We describe a case of recurrent ischemic stroke in a young patient presumably attributed to an impingement of the carotid artery by an elongated hyoid bone, and present other cases reported in the literature. Based on the imaging study as well as the lack of other findings, we attributed recurrent neurovascular events to the repetitive mechanical stimulation by the elongated hyoid bone that caused a vessel wall injury with subsequent thrombus and embolus. Given repeated recurrence under antiplatelet treatment, anticoagulation was added. The following 2-year follow-up showed no new neurologic events or any other complaints. Among the young, a broad spectrum of possibilities should be considered and we call attention to this infrequent etiology of ischemic stroke.

Abstract Introduction Only two studies investigated the associations between peak width of skeletonized mean diffusivity (PSMD) and age‐related cognitive alterations, whereas none of the studies investigated the association with vascular risk factors. Methods We evaluated 801 stroke‐ and dementia‐free elderlies with baseline and 3‐year follow‐up assessments. Regression analyses were used to assess the association between age‐related cognitive functions and PSMD. Simple mediation models were used to study the mediation effect of PSMD between vascular risk factors and age‐related cognitive outcomes. Results PSMD was negatively associated with processing speed at baseline and negatively associated with processing and memory scores at 3‐year follow‐up. The association between vascular risk factors and age‐related cognition was mediated by PSMD, as well as other diffusion tensor imaging markers. Discussion PSMD is preferred over other diffusion tensor imaging markers as it is sensitive to age‐related cognitive alterations and calculation is fully automated. PSMD is proposed as a research tool to monitor age‐related cognitive alterations.

Background: First-pass effect (FPE) is increasingly recognized as a predictor of good outcome in large vessel occlusion (LVO). This systematic review and meta-analysis aimed to elucidate the factors influencing recanalization after mechanical thrombectomy (MT) with FPE in treating acute ischemic stroke (AIS).Methods: Main databases were searched for relevant randomized controlled trials (RCTs) and observational studies reporting influencing factors of MT with FPE in AIS. Recanalization was assessed by the modified thrombolysis in cerebral ischemia (mTICI) score. Both successful (mTICI 2b-3) and complete recanalization (mTICI 2c-3) were observed. Risk of bias was assessed through different scales according to study design. The I2 statistic was used to evaluate the heterogeneity, while subgroup analysis, meta-regression, and sensitivity analysis were performed to investigate the source of heterogeneity. Visual measurement of funnel plots was used to evaluate publication bias.Results: A total of 17 studies and 6,186 patients were included. Among them, 2,068 patients achieved recanalization with FPE. The results of meta-analyses showed that age [mean deviation (MD):1.21,95% confidence interval (CI): 0.26–2.16; p = 0.012], female gender [odds ratio (OR):1.12,95% CI: 1.00–1.26; p = 0.046], diabetes mellitus (DM) (OR:1.17,95% CI: 1.01–1.35; p = 0.032), occlusion of internal carotid artery (ICA) (OR:0.71,95% CI: 0.52–0.97; p = 0.033), occlusion of M2 segment of middle cerebral artery (OR:1.36,95% CI: 1.05–1.77; p = 0.019), duration of intervention (MD: −27.85, 95% CI: −42.11–13.58; p < 0.001), time of onset to recanalization (MD: −34.63, 95% CI: −58.45–10.81; p = 0.004), general anesthesia (OR: 0.63,95% CI: 0.52–0.77; p < 0.001), and use of balloon guide catheter (BGC) (OR:1.60,95% CI: 1.17–2.18; p = 0.003) were significantly associated with successful recanalization with FPE. At the same time, age, female gender, duration of intervention, general anesthesia, use of BGC, and occlusion of ICA were associated with complete reperfusion with FPE, but M2 occlusion and DM were not.Conclusion: Age, gender, occlusion site, anesthesia type, and use of BGC were influencing factors for both successful and complete recanalization after first-pass thrombectomy. Further studies with more comprehensive observations indexes are need in the future.

In this study, an experimental hydrometeorological forecasting system was developed based on the Coupled Ocean-Atmosphere-Wave-Sediment Transport (COAWST) model. The system downloads global real-time ocean, atmosphere, and wave forcing data, producing regional forecasts every day. A coastal area in South China, encompassing Hainan Island, Leizhou Peninsula, and surrounding sea areas, was chosen as the study domain. A series of 72-hour forecasting simulations were conducted in the area, lasting from July 27 to August 31, 2019. The forecasts throughout August were chosen for evaluation with station observations, along with two sets of reanalysis data, ERA5 and CLDAS. The evaluation results revealed that the COAWST model had high potential for routine forecasting operations. The 24 h forecasts, with a lead time of 24 hours, had high accuracy, while the 48 h and 72 h forecasts did not differ greatly in terms of performance. The distributions of bias between forecast and reanalysis data showed obvious differences between land and sea, with more forecasted precipitation and lower temperatures in land grids than in sea grids. In most cases, the forecasts were closer to ERA5 in terms of means and other statistical measures. The forecasts enlarged the land-sea differences of temperature when compared with ERA5 and strengthened summer monsoon with more moisture transported to land areas. Resulting from that, a forecasted bias of lower surface pressure, higher air humidity, stronger south wind, and so forth was also detected over the domain but at low values.

It was reported that acupuncture could treat Alzheimer’s disease (AD) with the potential mechanisms remaining unclear. The aim of the study is to explore the effect of the combination stimulus of Hegu (LI4) and Taichong (LR3) on the resting-state brain networks in AD, beyond the default network (DMN). Twenty-eight subjects including 14 AD patients and 14 healthy controls (HCs) matched by age, gender, and educational level were recruited in this study. After the baseline resting-state MRI scans, the manual acupuncture stimulation was performed for 3 minutes, and then, another 10 minutes of resting-state fMRI scans was acquired. In addition to the DMN, five other resting-state networks were identified by independent component analysis (ICA), including left frontal parietal network (lFPN), right frontal parietal network (rFPN), visual network (VN), sensorimotor network (SMN), and auditory network (AN). And the impaired connectivity in the lFPN, rFPN, SMN, and VN was found in AD patients compared with those in HCs. After acupuncture, significantly decreased connectivity in the right middle frontal gyrus (MFG) of rFPN (P=0.007) was identified in AD patients. However, reduced connectivity in the right inferior frontal gyrus (IFG) (P=0.047) and left superior frontal gyrus (SFG) (P=0.041) of lFPN and some regions of the SMN (the left inferior parietal lobula (P=0.004), left postcentral gyrus (PoCG) (P=0.001), right PoCG (P=0.032), and right MFG (P=0.010)) and the right MOG of VN (P=0.003) was indicated in HCs. In addition, after controlling for the effect of acupuncture on HCs, the functional connectivity of the right cerebellum crus I, left IFG, and left angular gyrus (AG) of lFPN showed to be decreased, while the left MFG of IFPN and the right lingual gyrus of VN increased in AD patients. These findings might have some reference values for the interpretation of the combination stimulus of Hegu (LI4) and Taichong (LR3) in AD patients, which could deepen our understanding of the potential mechanisms of acupuncture on AD.

Background: Rapid and effective medical care for stroke is paramount to achieve maximal functional recovery. Because of the wide spreading of the coronavirus disease in 2019 (COVID-19), acute stroke care is negatively impacted. How much acute care for stroke has been affected during the pandemic remains to be assessed.Methods: The first-level response to major public health was launched from January 24th to April 29th, 2020 in Beijing to contain the spread of COVID-19. Based on a database connecting all 77 stroke centers, the quantity and quality in emergency care for stroke during the 97 lockdown days were compared with the equivalent period in 2019. During the pandemic, 15 of the 77 stroke centers were designated to receive patients sick with COVID-19. Subgroup analyses were carried out by different types of hospitals (designated and undesignated).Results: There were 1,281 and 2,354 stroke emergency hospital admissions in the lockdown period and the parallel period in 2019, respectively. A reduction of 45.6% in admission was shown in the lockdown period, with more reductions for hemorrhagic stroke (69.0%) compared with ischemic stroke (42.9%). More reductions happened in COVID-19 designated hospitals (52.6%) compared with undesignated hospitals (41.8%). The mean NIHSS score at hospital arrival was significantly higher in the lockdown period (9.4 ± 7.7 in 2020 vs. 8.4 ± 7.8 in 2019, P < 0.001). For the metrics measuring the quality of acute stroke care, the onset to door (OTD), onset to needle (ONT), and onset to recanalization (OTR) times didn't change significantly, while significant delays are shown for the door to CT scan (DTC, 1 min delay), door to needle (DTN, 4 min delays), and door to puncture (DTP, 29 min delays) times, which mainly happened in COVID-19 undesignated hospitals.Conclusions: Profound reductions in stroke hospital admissions and significant delays in emergency care for acute ischemic stroke occurred during the pandemic of COVID-19. Engagement and effective communication with all stakeholders including patients, health care providers, governmental policymakers, and other implementation partners are required for future success in similar crises.

Background and rationale: Although many therapies have been investigated for intracerebral hemorrhage (ICH), none have succeeded in improving the functional outcomes. Remote ischemic conditioning (RIC) has been proven to promote hematoma resolution and improve neurological outcomes in an ICH model; whether it is safe and feasible in patients with ICH remains unknown. This trial aims to assess the safety, feasibility, and preliminary efficacy of RIC in patients with ICH and to plan for a phase-2 study.Methods: A proof-of-concept, assessor-blinded, pilot open-label randomized controlled trial will be carried out with patients with ICH within 24–48 h of ictus. All participants will be randomly allocated to the intervention group and the control group with a 1:1 ratio (n = 20) and will be treated with standard managements according to the guidelines. Participants allocated to the intervention group will receive RIC once daily for 7 consecutive days. Cranial computed tomography examinations will be performed at baseline, and on days 3, 7, and 14. Neurological outcomes will be assessed at baseline, and on days 1 to 14, 30, and 90. The primary outcome to be tested is safety. Secondary tested outcomes include changes of hematoma and perihematomal edema volume, incidence of hematoma expansion, functional outcomes, and frequency of adverse events.Discussions: This study will be the first proof-of-concept randomized controlled trial to ascertain the safety, feasibility, and preliminary efficacy of RIC in patients with ICH, results of which will provide parameters for future studies and provide insights into the treatment of ICH.Trial Registration:Clinicaltrials.gov, identifier: NCT03930940.

BACKGROUND AND PURPOSE: The ring finger protein 213 (RNF213) gene R4810K variant, a susceptibility locus for moyamoya disease (MMD), has recently been identified to be associated with intracranial major artery stenosis/occlusion (ICASO) without satisfying the diagnostic criteria of MMD in the Japanese population. However, further studies are needed to determine whether this variant is associated with ICASO in other populations and whether R4810K variant-related ICASO could be categorized as MMD. The aim of this study is to elucidate whether the R4810K variant was associated with ICASO among the Han Chinese population and potential histopathology of R4810K variant-related ICASO. MATERIALS AND METHODS: We conducted a case–control study to evaluate association and performed high-resolution (HR) magnetic resonance imaging (MRI) to investigate arterial wall feature of ICASO. The R4810K variant was genotyped in 114 ICASO patients and 268 controls. Then, patients with R4810K variant-related ICASO were subjected to HR MRI examination and presumptively diagnosed based on the characteristics thus observed. STATISTICAL ANALYSIS: The relationship between R4810K variant and ICASO was evaluated by Fisher's exact test with odds ratios (OR) and 95% confidence interval (CI). RESULTS: The R4810K variant was associated with ICASO and increased the risk for ICASO (P < 0.01; OR: 20.2; 95% CI: 2.5–163.11). Presumptive MMD was diagnosed in all female patients with R4810K variant. However, presumptive intracranial atherosclerotic stenosis was diagnosed in one of three males harboring this variant. CONCLUSIONS: The R4810K variant is a genetic risk factor for ICASO among the Han Chinese population and that R4810K variant-related ICASO should be identified as MMD in female but not uncertain in male patients.

Abstract Serum albumin levels has been shown to predict outcome in ischemic stroke patients. We aimed to investigate the relationship between serum albumin levels and hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) in patients with acute stroke. 428 patients receiving intravenous rt-PA therapy were included from 2013 to 2016 and were categorized into two groups: low level ( 0.05). Low level of serum albumin within 24 hours may be an independent predictor of post-thrombolytic HT.

Recent studies have demonstrated a close relationship between regional cerebral blood flow (rCBF) and resting state functional connectivity changes in normal healthy people. However, little is known about the parameter changes in the most vulnerable regions in Alzheimer’s disease (AD). Forty AD patients and 30 healthy controls participated in this study. The data of resting-state perfusion and functional magnetic resonance imaging (fMRI) was collected. By using voxel-wise arterial spin labeling (ASL) perfusion, we identified several regions of altered rCBF in AD patients. Then, by using resting state fMRI analysis, including amplitude low frequency fluctuation (ALFF) and seed-based functional connectivity, we investigated the changes of functional activity and connectivity among the identified rCBF regions. We extracted cognition-related parameters and searched for a sensitive biomarker to differentiate the AD patients from the normal controls (NC). Compared with controls, AD patients showed special disruptions in rCBF, which were mainly located in the left posterior cingulate cortex (PCC), the left and right dorsolateral prefrontal cortex (DLPFC), the left inferior parietal lobule (IPL), the right middle temporal gyrus (MTG), the left middle occipital gyrus (MOG), and the left precuneus (PCu). ALFF was performed based on the seven regions identified by the ASL method, and AD patients presented significantly decreased ALFF in the left PCC, left IPL, right MTG, left MOG, and left PCu and increased ALFF in the bilateral DLPFC. We constituted the network based on the seven regions and found that there was decreased connectivity among the identified regions in the AD patients, which predicted a disruption in the default mode network (DMN), executive control network (ECN) and visual network (VN). Furthermore, these abnormal parameters are closely associated with cognitive performances in AD patients. We combined the rCBF and ALFF value of PCC/PCu as a biomarker to differentiate the two groups and reached a sensitivity of 85.3% and a specificity of 88.5%. Our findings suggested that there was disrupted rCBF, functional activity and connectivity in specific cognition-related regions in Alzheimer’s disease, which can be used as a valuable imaging biomarker for the diagnosis of AD.

Background and Purpose. Recently, several studies indicated the c.14576G>A variant on the ring finger protein 213 (RNF213), a founder variant of moyamoya diseases (MMD), was associated with non-MMD intracranial major artery stenosis/occlusion (non-MMD ICASO). We proposed that RNF213 variant-related ICASO including MMD might be a special entity with its own characteristics based on a genetic background. The aim of the study was to learn the clinical and vascular features of RNF213 variant-related ICASO. Moreover, we tried to explore the clinical significance of a testing variant in ICASO patients in China. Methods. Clinical material and routine image data were collected in 160 Chinese patients with ICASO, including 41 verified MMD and 119 non-MMD. DNA samples were extracted, and the c.14576G>A variant on RNF213 was genotyped. Then, the clinical and vascular features were compared between the patients with and without a relevant variant. Furthermore, the patients with RNF213 mutation were performed with high resolution magnetic resonance imaging (HR-MRI) examination to conclude features of the artery wall. Results. There were 16 (10%) patients (including 9 MMD and 7 non-MMD ICASO) presenting a heterozygous c.14576G>A variant while none of homozygote was found. Compared to the patients without the c.14576G>A variant, the variant group had more female, less symptomatic patients, and more possibility of having collateral vessels in vascular imaging. In the symptomatic subgroup, there is no significant difference in clinical presentation (p>0.05) between two groups. However, RNF213 variant-related ICASO had lower scores in NIHSS (1.0±3.0 vs. 3.9±5.0, pA variant on RNF213 may be a biomarker to good outcome of ICASO in Chinese. The variant-related ICASO was characterized by both features of MMD and ICAD diagnosed by HR-MRI.

Background Intracranial atherosclerotic disease tends to affect multiple arterial segments. Using whole‐brain vessel wall imaging, we sought to study the differences in plaque features among various types of plaques in patients with a recent unilateral anterior circulation ischemic stroke. Methods and Results Sixty‐one patients with unilateral anterior circulation ischemic stroke were referred to undergo whole‐brain vessel wall imaging (before and after contrast) within 1 month of symptom onset for intracranial atherosclerotic disease evaluations. Each plaque was classified as a culprit, probably culprit, or nonculprit lesion, according to its likelihood of causing the stroke. The associations between plaque features (thickening pattern, plaque‐wall contrast ratio, high signal on T1‐weighted images, plaque contrast enhancement ratio, enhancement grade, and enhancement pattern) and culprit lesions were estimated using mixed multivariable logistic regression after adjustment for maximum wall thickness. In 52 patients without motion corruption in whole‐brain vessel wall imaging, a total of 178 intracranial plaques in the anterior circulation were identified, including 52 culprit lesions (29.2%), 51 probably culprit lesions (28.7%), and 75 nonculprit lesions (42.1%). High signal on T1‐weighted images (adjusted odds ratio, 9.1; 95% confidence interval, 1.9–44.1; P=0.006), grade 2 (enhancement ratio of plaque ≥ enhancement ratio of pituitary) contrast enhancement (adjusted odds ratio, 17.4; 95% confidence interval, 1.8–164.9; P=0.013), and type 2 (≥50% cross‐sectional wall involvement) enhancement pattern (adjusted odds ratio, 10.1; 95% confidence interval, 1.3–82.2; P=0.030) were independently associated with culprit lesions. Conclusions High signal on T1‐weighted images, grade 2 contrast enhancement, and type 2 enhancement pattern are associated with cerebrovascular ischemic events, which may provide valuable insights into risk stratification.

In this study, we conducted an experimental model test and numerical thermal analysis to determine the temperature distribution and thermal gradients of mass concrete freezing shaft lining under the influence of low-temperature frozen soil wall. A non-scaled-down model was built with embedded thermocouple sensors to monitor the temperature distribution of the shaft lining and the frozen soil wall. Transient heat transfer analysis was conducted using ANSYS finite element software to validate the monitoring results of the model test. The temperature distribution at different points along the radial direction in the shaft lining and frozen soil wall are evaluated and compared by using finite element method and experimental work. The results are in good agreement and thus validated.

Recent researches have demonstrated that the insula is the crucial hub of the human brain networks and most vulnerable region of Alzheimer’s disease (AD). However, little is known about the changes of functional connectivity of insular subregions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (fMRI) data including 32 AD patients and 38 healthy controls (HCs). By defining three subregions of insula, we mapped whole-brain resting-state functional connectivity (RSFC) and identified several distinct RSFC patterns of the insular subregions: For positive connectivity, three cognitive-related RSFC patterns were identified within insula that suggest anterior-to-posterior functional subdivisions: (1) an dorsal anterior zone of the insula that exhibits RSFC with executive control network (ECN); (2) a ventral anterior zone of insula, exhibits functional connectivity with the salience network (SN); (3) a posterior zone along the insula exhibits functional connectivity with the sensorimotor network (SMN). In addition, we found significant negative connectivities between the each insular subregion and several special default mode network (DMN) regions. Compared with controls, the AD patients demonstrated distinct disruption of positive RSFCs in the different network (ECN and SMN), suggesting the impairment of the functional integrity. There were no differences of the positive RSFCs in the SN between the two groups. On the other hand, several DMN regions showed increased negative RSFCs to the sub-region of insula in the AD patients, indicating compensatory plasticity. Furthermore, these abnormal insular subregions RSFCs are closely correlated with cognitive performances in the AD patients. Our findings suggested that different insular subregions presented distinct RSFC patterns with various functional networks, which are differently affected in the AD patients.

Acupuncture has been used in the therapy of Alzheimer disease (AD); however, its neural mechanisms are still unclear. The aim of this study is to examine the effect of acupuncture on the functional connectivity in AD by using resting-state functional magnetic resonance imaging (rs-fMRI). Twenty-eight subjects (14 AD and 14 normal controls) participated in this study. The rs-fMRI data were acquired before and after acupuncture stimulation at the acupoints of Tai chong (Liv3) and Hegu (LI4). During the baseline resting state, by using the amplitude of low-frequency fluctuations (ALFF), we found a significantly decreased or increased ALFF in the AD patients relative to the controls. These regions were located in the right superior frontal gyrus (SFG), left postcentral gyrus, subgenual cingulate cortex (SCC), right middle cingulate cortex (MCC), right inferior frontal gyrus (IFG), right hippocampus and the right inferior temporal gyrus (ITG). Then, we selected these brain regions as seeds to investigate whether regional activity and functional connectivity could be modulated by acupuncture in the AD patients. When compared to the pre-acupuncture stage, several of the above regions showed an increased or decreased ALFF after acupuncture in the AD patients. In addition, the functional connectivity between the hippocampus and the precentral gyrus showed enhancement after acupuncture in the AD patients. Finally, there were close correlations between the functional activity, connectivity and clinical performance in the AD patients. The current study confirmed that acupuncture at Tai chong (Liv3) and He gu (LI4) can modulate functional activity and connectivity of specific cognition-related regions in AD patients.

Alzheimer’s disease (AD) is the most common cause of dementia. Previous studies have found disrupted resting state functional connectivities (rsFCs) in various brain networks in the AD patients. However, few studies have focused on the rsFCs of the cerebellum and its sub-regions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (rs-fMRI) data including 32 AD patients and 38 healthy controls (HCs). We selected two cognitive-related subregions of the cerebellum as seed region and mapped the whole-brain rsFCs for each subregion. We identified several distinct rsFC patterns of the two cognitive-related cerebellar subregions: default-mode network (DMN), frontoparietal network (FPN), visual network (VN) and sensorimotor network (SMN). Compared with the controls, the AD patients showed disrupted rsFCs in several different networks (DMN, VN and SMN), predicting the impairment of the functional integration in the cerebellum. Notably, these abnormal rsFCs of the two cerebellar subregions were closely associated with cognitive performance. Collectively, we demonstrated the distinct rsFCs patterns of cerebellar sub-regions with various functional networks, which were differentially impaired in the AD patients.

Functional connectivity in default mode network (DMN) may be changed in Alzheimer's disease (AD) patients and related risk populations, such as amnestic mild cognitive impairment (aMCI) patients and APOE ε4 carriers. Exploring DMN changes and related behavioral performance of APOE ε4 population might provide valuable evidence for better understanding the development of AD.Subjects were enrolled from a population-based cohort established in a multi-center study in China. Forty-nine cognitive normal individuals were enrolled after standardized cognitive evaluations, MRI examination and APOE genotyping. Regions of interest (ROI)-based functional connectivity analyses were performed, and voxel-based analyses were used to validate these findings. The correlation between DMN functional connectivity and behavioral performance was further evaluated between APOE ε4ε3 and ε3ε3 carriers.Comparing to ε3ε3 carriers, functional connectivity between left parahippocampal gyrus and right superior frontal cortex (LPHC-R.Sup.F), left parahippocampal gyrus and medial prefrontal cortex (ventral) (LPHC-vMPFC) were significantly increased in ε4ε3 carriers, while connectivity between cerebellar tonsils and retrosplenial was decreased. LPHC-R.Sup.F connectivity was positively correlated with the changes of delay recall from baseline to follow-up (r = 0.768, p = 0.009), while LPHC-vMPFC connectivity had a positive correlation with MMSE at baseline (r = 0.356, p = 0.018), and a negative correlation with long-delayed recognition at follow-up (r = -0.677, p = 0.031). Significantly increased functional connectivity in vMPFC was confirmed in voxel-based analyses by taking LPHC as seed region.APOE ε4 carriers present both increased and decreased functional connectivity in DMN, which is correlated with clinical cognitive performances. DMN changes might be an early sign for cognitive decline.

Our objective is to clarify the effects of acupuncture on hippocampal connectivity in patients with Alzheimer disease (AD) using functional magnetic resonance imaging (fMRI). Twenty-eight right-handed subjects (14 AD patients and 14 healthy elders) participated in this study. Clinical and neuropsychological examinations were performed on all subjects. MRI was performed using a SIEMENS verio 3-Tesla scanner. The fMRI study used a single block experimental design. We first acquired baseline resting state data during the initial 3 minutes and then performed acupuncture stimulation on the Tai chong and He gu acupoints for 3 minutes. Last, we acquired fMRI data for another 10 minutes after the needle was withdrawn. The preprocessing and data analysis were performed using statistical parametric mapping (SPM5) software. Two-sample t-tests were performed using data from the two groups in different states. We found that during the resting state, several frontal and temporal regions showed decreased hippocampal connectivity in AD patients relative to control subjects. During the resting state following acupuncture, AD patients showed increased connectivity in most of these hippocampus related regions compared to the first resting state. In conclusion, we investigated the effect of acupuncture on AD patients by combing fMRI and traditional acupuncture. Our fMRI study confirmed that acupuncture at Tai chong and He gu can enhance the hippocampal connectivity in AD patients.

The baseline and longitudinal changes of the posterior cingulate cortex (PCC) connectivity were assessed in order to clarify the neural mechanism of mild cognitive impairment (MCI). Twenty-eight right-handed subjects (14 MCI patients and 14 healthy elders) participated in this study. Clinical and neuropsychological examinations were performed on all the subjects. PCC functional connectivity was studied by examining the correlation between low frequency fMRI signal fluctuations in the PCC and those in all the other brain regions. Additionally, we traced all the MCI patients and compared their PCC connectivity in the initial stage and that in 3 years later. We also explored the relationship between the PCC functional connectivity strength and cognitive performances. Our results are as follows: Functional connectivity between the PCC and a set of regions is decreased in MCI patients. Most of these regions are within the default mode network (DMN). Three years later, the regions of superior frontal gyrus (SFG) and middle frontal gyrus (MFG) presented further decreased connectivity to the PCC in MCI. In addition, we also find enhanced functional connectivity between PCC and medial prefrontal cortex (MPFC), PCC and anterior cingulate cortex (ACC) in MCI patients. At last, our research also shows that the PCC connectivity with some regions significantly correlates with the cognitive performances of patients as measured by mini-mental state examination (MMSE), and California verbal learning test (CVLT) scores. The baseline and longitudinal changes of the PCC connectivity in our study suggest that impairment and compensation coexist in the disease progress of MCI patients.

We aim to clarify the mechanisms of acupuncture in treating mild cognitive impairment (MCI) and Alzheimer disease (AD) by using functional magnetic resonance imaging (fMRI). Thirty-six right-handed subjects (8 MCI patients, 14 AD patients, and 14 healthy elders) participated in this study. Clinical and neuropsychological examinations were performed on all the subjects. MRI data acquisition was performed on a SIEMENS verio 3-Tesla scanner. The fMRI study used a single block experimental design. We first acquired the baseline resting state data in the initial 3 minutes; we then acquired the fMRI data during the procession of acupuncture stimulation on the acupoints of Tai chong and Hegu for the following 3 minutes. Last, we acquired fMRI data for another 10 minutes after the needle was withdrawn. The preprocessing and data analysis were performed using the statistical parametric mapping (SPM8) software. Then the two-sample t-tests were performed between each two groups of different states. We found that during the resting state, brain activities in AD and MCI patients were different from those of control subjects. During the acupuncture and the second resting state after acupuncture, when comparing to resting state, there are several regions showing increased or decreased activities in MCI, AD subjects compared to normal subjects. Most of the regions were involved in the temporal lobe and the frontal lobe, which were closely related to the memory and cognition. In conclusion, we investigated the effect of acupuncture in AD and MCI patients by combing fMRI and traditional acupuncture. Our fMRI study confirmed that acupuncture at Tai chong (Liv3) and He gu (LI4) can activate certain cognitive-related regions in AD and MCI patients.

Our study aimed to construct a predictive model for identifying instances of futile recanalization in patients with anterior circulation occlusion acute ischemic stroke (AIS) who achieved complete reperfusion following endovascular therapy. We included 173 AIS patients who attained complete reperfusion, as indicated by a Modified Thrombolysis in Cerebral Infarction (mTICI) scale score of 3. Our approach involved a thorough analysis of clinical factors, imaging biomarkers, and potential no-reflow biomarkers through both univariate and multivariate analyses to identify predictors of futile recanalization. The comprehensive model includes clinical factors such as age, presence of diabetes, admission NIHSS score, and the number of stent retriever passes; imaging biomarkers like poor collaterals; and potential no-reflow biomarkers, notably disrupted blood-brain barrier (OR 4.321, 95% CI 1.794-10.405; p = 0.001), neutrophil-to-lymphocyte ratio (NLR; OR 1.095, 95% CI 1.009-1.188; p = 0.030), and D-dimer (OR 1.134, 95% CI 1.017-1.266; p = 0.024). The model demonstrated high predictive accuracy, with a C-index of 0.901 (95% CI 0.855-0.947) and 0.911 (95% CI 0.863-0.954) in the original and bootstrapping validation samples, respectively. Notably, the comprehensive model showed significantly improved predictive performance over models that did not include no-reflow biomarkers, evidenced by an integrated discrimination improvement of 8.86% (95% CI 4.34%-13.39%; p < 0.001) and a categorized reclassification improvement of 18.38% (95% CI 3.53%-33.23%; p = 0.015). This model, which leverages the potential of no-reflow biomarkers, could be especially beneficial in healthcare settings with limited resources. It provides a valuable tool for predicting futile recanalization, thereby informing clinical decision-making. Future research could explore further refinements to this model and its application in diverse clinical settings. [ABSTRACT FROM AUTHOR]