Exploring the link between brain topological resilience and cognitive performance in the context of aging and vascular risk factors: A cross-ethnicity population-based study.

Brain aging is typically associated with a significant decline in cognitive performance. Vascular risk factors (VRF) and subsequent atherosclerosis (AS) play a major role in this process. Brain resilience reflects the brain's ability to withstand external perturbations, but the relationship of brain resilience with cognition during the aging process remains unclear. Here, we investigated how brain topological resilience (BTR) is associated with cognitive performance in the face of aging and vascular risk factors. We used data from two cross-ethnicity community cohorts, PolyvasculaR Evaluation for Cognitive Impairment and Vascular Events (PRECISE, n = 2220) and Sydney Memory and Ageing Study (MAS, n = 246). We conducted an attack simulation on brain structural networks based on k-shell decomposition and node degree centrality. BTR was defined based on changes in the size of the largest subgroup of the network during the simulation process. Subsequently, we explored the negative correlations of BTR with age, VRF, and AS, and its positive correlation with cognitive performance. Furthermore, using structural equation modeling (SEM), we constructed path models to analyze the directional dependencies among these variables, demonstrating that aging, AS, and VRF affect cognition by disrupting BTR. Our results also indicated the specificity of this metric, independent of brain volume. Overall, these findings underscore the supportive role of BTR on cognition during aging and highlight its potential application as an imaging marker for objective assessment of brain cognitive performance.

Absolute monocyte counts could predict disease activity and secondary loss of response of patients with Crohn's disease treated with anti-TNF-α drug.

BACKGROUND: Assessing Crohn's disease (CD) activity is critical for monitoring disease progression. In CD, monocytes could release TNF-α. Thus, it is extremely important to study its role in the disease activity and loss of response to anti-TNF-α biologics. METHODS: In this study, we collected CD patients treated with biologics from January 2017 to May 2022. Indicators associated with disease activity were evaluated by Spearman correlation analysis and Mann-Whitney U test. Specifically, logistic analyses were used to explore the predictors of primary nonresponse (PNR) and secondary loss of response (SLOR) within 1 year of anti-TNF-α agents. In addition, a nomogram was developed for therapeutic effect prediction. RESULTS: 283 patients with CD were identified. Disease activity group, defined as CDAI equal to or greater than 150, had significant elevated absolute monocyte counts than disease remission group based on CDAI score (p = 0.019, Z = -2.354). Logistic analyses showed that absolute monocyte counts could be an independent predictor of 1-year SLOR of anti-TNF-α agents in CD patients (p = 0.013). A nomogram established based on gender, absolute monocyte counts, and hemoglobin could predict SLOR within 1 year of anti-TNF-α agents reliably. CONCLUSION: The results of this study support the utility of absolute monocyte counts detecting disease activity and anti-TNF-α therapy effect in patients with CD.

Gait speed at the acute phase predicted health-related quality of life at 3 and 12 months after stroke: a prospective cohort study.

OBJECTIVE: To investigate the association between acute-phase gait speed and health-related quality of life (HRQoL) at 3 and 12 months post-stroke. DESIGN: Prospective cohort study. SUBJECTS/PATIENTS: 1,475 patients with first-ever ischaemic stroke. METHODS: The patients were divided into 3 groups according to tertiles of gait speed, namely ≤0.8, 0.8-1.1, ≥1.1 m/s. Gait speed was assessed by the 10-m walking test within 2 weeks of hospitalization for acute stroke and before the rehabilitation programme. HRQoL measurements include the 3-level EuroQol five dimensions (EQ-5D-3L) index and EuroQoL visual analogue scale (EQ-VAS) scores. Linear and logistic regression analyses were used to identify associations between gait speed and HRQoL. RESULTS: Adjusted for all covariates, the highest gait speed tertile group were associated with higher EQ-5D-3L index (B = 0.0303 and B = 0.0228, respectively, p < 0.001), and higher EQ-VAS (B = 3.3038 and B = 3.8877, respectively, p < 0.001), and lower odds of having problems with mobility (OR = 2.55 [95% CI: 0.141-0.458] and 0.485 [0.289-0.812], respectively, p < 0.01), self-care (OR = 0.328 [95% CI: 0.167-0.646] and 0.412 [0.217-0.784], respectively, p < 0.01), and usual activities (OR = 0.353 [95% CI: 0.211-0.590] and 0.325 [0.198-0.536], respectively, p < 0.0001) at 3 and 12 months, and pain/discomfort at 12 months (OR = 0.558 [95% CI:0.335-0.930], p < 0.05). CONCLUSION: Acute-phase gait speed was predictive of post-stroke HRQoL at 3 and 12 months, especially when associated with domain-specific EQ-5D-3L.

Anticancer potential of grifolin in lung cancer treatment through PI3K/AKT pathway inhibition.

Objective: Grifolin is a natural secondary metabolite isolated from edible fruiting bodies of the mushroom Albatrellus confluens. Grifolin has antitumor activities in several types of cancer. We aimed to determine the effects of grifolin on lung cancer. Methods: We determined the proliferation, migration, invasion, and apoptosis of lung cancer cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Ethynyl deoxyuridine, colony formation, wound scratch, transwell, flow cytometry, and xenograft mouse assays. Molecular docking evaluated the binding relation between grifolin and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). The levels of PIK3CA, AKT, and p-AKT were measured by western blot. Results: Grifolin (10, 20, or 40 µM) inhibited the proliferation, migration, and invasion of lung cancer cells, and induced cell cycle arrest and apoptosis. Grifolin also decreased CDK4, CDK6, and CyclinD1 expression and significantly decreased PIK3CA and p-AKT expression in lung cancer cells. These anticancer effects were abolished by 740Y-P. Conclusions: Grifolin regulates the PI3K/AKT pathway, thus inhibiting lung cancer progression.

Ninety-Day Stroke Recurrence in Minor Stroke: Systematic Review and Meta-Analysis of Trials and Observational Studies.

BACKGROUND: Risk of recurrence after minor ischemic stroke is usually reported with transient ischemic attack. No previous meta-analysis has focused on minor ischemic stroke alone. The objective was to evaluate the pooled proportion of 90-day stroke recurrence for minor ischemic stroke, defined as a National Institutes of Health Stroke Scale severity score of ≤5. METHODS AND RESULTS: Published papers found on PubMed from 2000 to January 12, 2021, reference lists of relevant articles, and experts in the field were involved in identifying relevant studies. Randomized controlled trials and observational studies describing minor stroke cohort with reported 90-day stroke recurrence were selected by 2 independent reviewers. Altogether 14 of 432 (3.2%) studies met inclusion criteria. Multilevel random-effects meta-analysis was performed. A total of 6 randomized controlled trials and 8 observational studies totaling 45 462 patients were included. The pooled 90-day stroke recurrence was 8.6% (95% CI, 6.5-10.7), reducing by 0.60% (95% CI, 0.09-1.1; P=0.02) with each subsequent year of publication. Recurrence was lowest in dual antiplatelet trial arms (6.3%, 95% CI, 4.5-8.0) when compared with non-dual antiplatelet trial arms (7.2%, 95% CI, 4.7-9.6) and observational studies 10.6% (95% CI, 7.0-14.2). Age, hypertension, diabetes, ischemic heart disease, or known atrial fibrillation had no significant association with outcome. Defining minor stroke with a lower National Institutes of Health Stroke Scale threshold made no difference - score ≤3: 8.6% (95% CI, 6.0-11.1), score ≤4: 8.4% (95% CI, 6.1-10.6), as did excluding studies with n<500%-7.3% (95% CI, 5.5-9.0). CONCLUSIONS: The risk of recurrence after minor ischemic stroke is declining over time but remains important.

Elevated gut microbiota metabolite bile acids confer protective effects on clinical prognosis in ischemic stroke patients.

Background: There is evidence of an association between the gut microbiota and progression of stroke. However, the relationship between gut microbial metabolites, specifically bile acids (BAs), and post-ischemic stroke disability and poor functional outcomes remains unexplored. Methods: Patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in the Third China National Stroke Registry were grouped according to total bile acid (TBA) quartile on admission. Association of TBA with disability and poor functional outcomes were evaluated using logistic regression models and restricted cubic splines. Results: Data for 9,536 patients were included. After adjusting for confounders, the risks of disability and poor functional outcomes were significantly lower in the highest TBA quartile than in the lowest TBA quartile at the 3-month follow-up, with respective odds ratios (ORs) of 0.65 (95% confidence interval [CI] 0.55-0.78; p < 0.001) and 0.66 (95% CI 0.55-0.78, p < 0.001). Each standard deviation increase in the TBA level reduced the risks of disability and poor functioning outcomes by 10% (adjusted ORs 0.9 [95% CI 0.83-0.98; p = 0.01] and 0.9 [95% CI 0.83-0.97; p < 0.001], respectively). This association remained similar at the 1-year follow-up. After stratification by TOAST subtype, the risk of disability or a poor functional outcome in patients with the large-artery atherosclerosis or "other" subtype was significantly lower in the highest quartile than in the lowest quartile (p < 0.05). Conclusion: Serum TBA is an independent risk factor for disability and poor functional outcomes after AIS or TIA, and exerts a protective effects on brain.

Establishment of Patient-Derived Xenograft Mouse Model with Human Osteosarcoma Tissues.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Despite the development of new treatment plans in recent years, the prognosis for osteosarcoma patients has not significantly improved. Therefore, it is crucial to establish a robust preclinical model with high fidelity. The patient-derived xenograft (PDX) model faithfully preserves the genetic, epigenetic, and heterogeneous characteristics of human malignancies for each patient. Consequently, PDX models are considered authentic in vivo models for studying various cancers in transformation studies. This article presents a comprehensive protocol for creating and maintaining a PDX mouse model that accurately mirrors the morphological features of human osteosarcoma. This involves the immediate transplantation of freshly resected human osteosarcoma tissue into immunocompromised mice, followed by successive passaging. The described model serves as a platform for studying the growth, drug resistance, relapse, and metastasis of osteosarcoma. Additionally, it aids in screening the target therapeutics and establishing personalized treatment schemes.

A Multiplex Fluorescence of Loop Primer Upon Self-Dequenching Loop-Mediated Isothermal Amplification Assay for the Detection of Epstein-Barr Virus and Human Parvovirus B19 in Clinical Transplant Samples.

Viral infections are major causes of mortality in solid-organ and hematopoietic stem cell transplant recipients. Epstein-Barr virus (EBV) and Parvovirus B19 (B19V) are among the common viral infections after transplantation and were recommended for increased screening in relevant guidelines. Therefore, the development of rapid, specific, and cost-effective diagnostic methods for EBV and B19V is of paramount importance. We applied Fluorescence of Loop Primer Upon Self-Dequenching Loop-mediated Isothermal Amplification (FLOS-LAMP) for the first time to develop a novel multiplex assay for the detection of EBV and B19V; the fluorophore attached to the probe are self-quenched in unbound state. After binding to the dumbbell-shaped DNA target, the fluorophore is dequenched, resulting in fluorescence development. The novel multiplex FLOS-LAMP assay was optimized by testing various ratios of primer sets. This novel assay, with great specificity, did not cross-react with the common virus. For the detection of EBV and B19V, the limits of detection could reach 969 and 798 copies/µL, respectively, and the assay could be completed within 25 min. Applying this novel assay to detect 200 clinical transplant individuals indicated that the novel assay had high specificity and good sensitivity. We developed multiplex FLOS-LAMP assay for the detection of EBV and B19V, which has the potential to become an important tool for clinical transplant patient screening.

Rehabilitation with brain-computer interface and upper limb motor function in ischemic stroke: A randomized controlled trial.

BACKGROUND: Upper limb motor dysfunction is a major problem in the rehabilitation of patients with stroke. Brain-computer interface (BCI) is a kind of communication system that converts the "ideas" in the brain into instructions and has been used in stroke rehabilitation. This study aimed to investigate the efficacy and safety of BCI in rehabilitation training on upper limb motor function among patients with ischemic stroke. METHODS: This was an investigator-initiated, multicenter, randomized, open-label, blank-controlled clinical trial with blinded outcome assessment conducted at 17 centers in China. Patients were assigned in a 1:1 ratio to the BCI group or the control group based on traditional rehabilitation training. The primary efficacy outcome is the difference in improvement of the Fugl-Meyer Assessment upper extremity (FMA-UE) score between two groups at month 1 after randomization. The safety outcomes were any adverse events within 3 months. FINDINGS: A total of 296 patients with ischemic stroke were enrolled and randomly allocated to the BCI group (n = 150) and the control group (n = 146). The primary efficacy outcomes of FMA-UE score change from baseline to 1 month were 13.17 (95% confidence interval [CI], 11.56-14.79) in the BCI group and 9.83 (95% CI, 8.19-11.47) in the control group (mean difference between groups was 3.35; 95% CI, 1.05-5.65; p = 0.0045). Adverse events occurred in 33 patients (22.00%) in the BCI group and in 31 patients (21.23%) in the control group. CONCLUSIONS: BCI rehabilitation training can further improve upper limb motor function based on traditional rehabilitation training in patients with ischemic stroke. This study was registered at ClinicalTrials.gov: NCT04387474. FUNDING: This work was supported by the National Key R&D Program of China (2018YFC1312903), the National Key Research and Development Program of China (2022YFC3600600), the Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University (CCMU2022ZKYXZ009), the Beijing Natural Science Foundation Haidian original innovation joint fund (L222123), the Fund for Young Talents of Beijing Medical Management Center (QML20230505), and the high-level public health talents (xuekegugan-02-47).

LDL-C Levels and Bleeding Risk in Patients Taking DAPT After Minor Ischemic Stroke or TIA.

Importance: Evidence on the bleeding risk associated with low-density lipoprotein cholesterol (LDL-C) levels in patients receiving dual antiplatelet therapy (DAPT) remains sparse. Objective: To investigate the association of LDL-C levels with bleeding risk in patients with minor ischemic stroke (MIS) or high-risk transient ischemic attack (HRTIA) receiving DAPT. Design, Setting, and Participants: This cohort study was an analysis of pooled data from 2 randomized, double-blind, placebo-controlled clinical trials in China of patients with MIS or HRTIA who were receiving DAPT: the CHANCE (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) trial enrolled patients at 114 sites from October 2009 to July 2012, and the CHANCE-2 enrolled patients at 202 centers from September 2019 to March 2021. Both sets of patients were followed up for 90 days. Data analysis was performed from August 2022 to May 2023. Exposures: Baseline LDL-C levels and receipt of ticagrelor-aspirin and clopidogrel-aspirin DAPT. Main Outcomes and Measures: The primary outcome was any bleeding, and the secondary outcome was severe or moderate bleeding within 3 months after randomization. The association of LDL-C levels and all outcomes was assessed by using the Cox proportional hazard model. Hazard ratios (HRs) with 95% CIs were calculated on univariable (unadjusted) Cox regression models. Adjusted HRs (aHRs) and their 95% CIs were calculated on multivariable Cox regression models. Results: In total, 8996 patients with acute MIS or HRTIA who were receiving DAPT were included in the 2 trials, of whom 1066 without serum specimens and 490 patients with missing baseline LDL-C value were excluded. Finally, 7440 patients with DAPT (4486 in the clopidogrel-aspirin group and 2954 in the ticagrelor-aspirin group) were included in this study. The median (IQR) age was 64.32 (56.56-71.30) years, and 2479 patients (33.32%) were women. A total of 270 (3.63%) bleeding events were reported at 3 months, and LDL-C less than 70 mg/dL was associated with an increased risk of both any bleeding (aHR, 1.48; 95% CI, 1.03-2.12), and severe or moderate bleeding (aHR, 2.78; 95% CI, 1.18-6.53). The risk of any bleeding was increased at lower LDL-C levels in the ticagrelor-aspirin group (aHR, 1.71; 95% CI, 1.08-2.72). However, an increased risk of any bleeding was not observed in the clopidogrel-aspirin group (aHR, 1.30; 95% CI, 0.73-2.30). There was no significant association between LDL-C levels and the risk of severe or moderate bleeding in either the ticagrelor-aspirin or clopidogrel-aspirin group. Conclusions and Relevance: These findings suggest that low LDL-C levels are associated with an increased bleeding risk within 3 months among patients with MIS or HRTIA receiving DAPT, especially those taking ticagrelor-aspirin. Weighing the risks and benefits is crucial when simultaneously considering the selection of LDL-C target strategies and DAPT regimens among these patients.

DACNN-aided nonlinear equalizer for a probabilistic shaping coherent optical communication system.

The probabilistic shaping (PS) technique is a key technology for fiber optic communication systems to further approach the Shannon limit. To solve the problem that nonlinear equalizers are ineffective for probabilistic shaping optical communication systems with non-uniform distribution, a distribution alignment convolutional neural network (DACNN)-aided nonlinear equalizer is proposed. The approach calibrates the equalizer using the probabilistic shaping prior distribution, which reduces the training complexity and improves the performance of the equalizer simultaneously. Experimental results show nonlinear equalization of 120 Gb/s PS 64QAM signals in a 375 km transmission scenario. The proposed DACNN equalizer improves the receiver sensitivity by 2.6 dB and 1.1 dB over the Volterra equalizer and convolutional neural network (CNN) equalizer, respectively. Meanwhile, DACNN converges with fewer training epochs than CNN, which provides great potential for mitigating the nonlinear distortion of PS signals in fiber optic communication systems.

16QAM optical signal generation scheme based on weighted optimal Euclidean distance.

A two-dimensional signal constellation scheme for binary uniform memoryless source transmission in optical fiber channels is studied in this paper. In geometric shaping (GS), optimization algorithms are usually used to change the overall position of constellation points while maintaining the probability of constellation points unchanged. Different optimization functions are used to allocate the position of constellation symbols, thereby improving constellation performance. A 16 quadrature amplitude modulation (QAM) optical signal generation scheme based on weighted optimal Euclidean distance is proposed in this paper. In order to obtain the best constellation diagram and increase the shaping gain, the weighted optimal Euclidean distance that can minimize the bit error rate (BER) over multiple iterative optimizations is used as the objective function. On the one hand, the proposed 16QAM optical signal generation scheme based on weighted optimal Euclidean distance always outperforms the uniform square 16QAM and the uniform circle 16QAM schemes in the back to back (BTB) transmission. On the other hand, after analyzing the simulation demonstration in a 50GBaud coherent optical communication system over 3000 km, results demonstrate that the optical signal to noise ratio (OSNR) performance of this system is better than that of the uniform square 16QAM and the uniform circle 16QAM, which is improved by 0.52 dB and 0.85 dB, respectively. In addition, the proposed 16QAM system increases the transmission distance by 989 km and 741 km, respectively, compared to the other two systems. The performance confirms that the proposed novel 16QAM scheme, to the best of our knowledge, can effectively improve the reliability and transmission distance. Therefore, the proposed scheme has a certain development prospect in the future long-distance transmission of high-speed optical fiber communication.

A clinically actionable and explainable real-time risk assessment framework for stroke-associated pneumonia.

The current medical practice is more responsive rather than proactive, despite the widely recognized value of early disease detection, including improving the quality of care and reducing medical costs. One of the cornerstones of early disease detection is clinically actionable predictions, where predictions are expected to be accurate, stable, real-time and interpretable. As an example, we used stroke-associated pneumonia (SAP), setting up a transformer-encoder-based model that analyzes highly heterogeneous electronic health records in real-time. The model was proven accurate and stable on an independent test set. In addition, it issued at least one warning for 98.6 % of SAP patients, and on average, its alerts were ahead of physician diagnoses by 2.71 days. We applied Integrated Gradient to glean the model's reasoning process. Supplementing the risk scores, the model highlighted critical historical events on patients' trajectories, which were shown to have high clinical relevance.

Intravenous alteplase in minor nondisabling ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: Minor ischemic stroke, defined as National Institute of Health Stroke Scale score of 0-5 on admission, represents half of all acute ischemic strokes. The role of intravenous alteplase (IVA) among patients with minor stroke is inconclusive; therefore, we evaluated clinical outcomes of these patients treated with or without IVA. MATERIALS AND METHODS: We searched Medline, Embase, Scopus, and the Cochrane library until August 1, 2023. Inclusion was restricted to the English literature of studies that reported on minor nondisabling stroke patients treated with or without IVA. Odds ratios (ORs) with their corresponding 95% CIs were utilized using a random-effects model. Efficacy outcomes included rates of excellent (modified Rankin scale [mRS] of 0-1) and good (mRS of 0-2) functional outcome at 90 days. The main safety outcome was symptomatic intracerebral hemorrhage (sICH). RESULTS: Five eligible studies, two RCTs and three observational studies, comprising 2764 patients (31.8% female) met inclusion criteria. IVA was administered to 1559 (56.4%) patients. Pooled analysis of the two RCTs revealed no difference between the two groups in terms of 90-days excellent functional outcomes (OR 0.76 [95% CI, 0.51-1.13]; I2 = 0%) and sICH rates (OR 3.76 [95% CI, 0.61-23.20]). No significant differences were observed between the groups in terms of good functional outcomes, 90-day mortality, and 90-day stroke recurrence. CONCLUSION: This meta-analysis of minor nondisabling stroke suggests that IVA did not prove more beneficial compared to no-IVA.

Plasma sACE-2 and risk of recurrent stroke: a nested case-control analysis.

Introduction The angiotensin-converting enzyme-2 (ACE-2) and its shedding product [soluble ACE-2 (sACE-2)] are implicated in adverse cardiovascular outcomes. However, the relationship between sACE-2 and stroke recurrence is unknown. Herein, we examined the relationship of sACE-2 with stroke recurrence in patients with ischemic stroke or transient ischemic attack (TIA). Methods Data were obtained from the Third China National Stroke Registry (CNSR-Ⅲ). Eligible cases consisted of 494 patients who developed recurrent stroke within 1-year follow-up, 494 controls were selected using age- and sex- matched with a 1:1 case-control ratio. Conditional logistic regressions were used to evaluate the association between sACE-2 and recurrent stroke. The main outcomes were recurrent stroke within 1 year. Results Among 988 patients included in this study, the median (interquartile range) of sACE-2 was 25.17 (12.29-45.56) ng/mL. After adjustment for conventional confounding factors, the odds ratio with 95% confidence interval in the highest quartile versus the lowest quartile was 1.68 (1.12-2.53) for recurrent stroke within 1-year follow-up. Subgroup analysis showed that the association between elevated plasma level of sACE-2 and stroke recurrence was significant in patients with higher systemic inflammation, as indicated by high sensitivity C reactive protein (hsCRP) ≥ 2 mg/L (adjusted OR: 2.33 [95% CI, 1.15-4.72]) and neutrophil (NEUT) counts ≥ median (adjusted OR: 2.66 [95% CI, 1.35-5.23]), but not significant in patients with lower systemic inflammation. Discussion Elevated plasma sACE-2 concentration was associated with increased risk of recurrent stroke.

Rationale and design of Treatment of Acute Ischaemic Stroke with Edaravone Dexborneol II (TASTE-2): a multicentre randomised controlled trial.

BACKGROUND: Edaravone dexborneol is believed to be a novel cytoprotective drug, demonstrating a synergistic combination of antioxidative and anti-inflammatory properties in animal models. The Treatment of Acute Ischaemic Stroke with Edaravone Dexborneol (TASTE) trial demonstrated its superior efficacy over edaravone alone for acute ischaemic stroke (AIS) patients. However, its efficacy in individuals undergoing endovascular therapy (EVT) remains uncertain. AIM: To clarify the rationale and design of the TASTE II (TASTE-2) trial. DESIGN: The TASTE-2 is a multicentre, double-blind, randomised, placebo-controlled trial designed to evaluate the efficacy and safety of edaravone dexborneol in patients with AIS and large-vessel occlusion in the anterior circulation. The eligible participants, presenting with a National Institute of Health Stroke Scale score between 6 and 25 (range 0-42, with larger values suggesting severe neurological dysfunction) and an Alberta Stroke Program Early Computed Tomography Score ranging from 6 to 10 (range 0-10, with smaller values suggesting larger infarction) within the initial 24 hours after symptom onset, will be randomly allocated to either the edaravone dexborneol group or the placebo group in equal proportions prior to thrombectomy. The treatment will be continuously administered for a duration of 10-14 days. A follow-up period of 90 days will be implemented for all participants. STUDY OUTCOMES: The primary efficacy outcome is defined as achieving favourable functional independence, measured by a modified Rankin Scale of 0-2 at 90 days. The primary safety outcome focuses on the incidence of serious adverse events. DISCUSSION: The TASTE-2 trial will provide evidence to determine whether the administration of edaravone dexborneol in AIS patients undergoing EVT could yield significant improvements in neurological function.

Subtype-Specific Association of Mitochondrial DNA Copy Number With Poststroke/TIA Outcomes in 10†241 Patients in China.

BACKGROUND: Mitochondrial DNA copy number (mtDNA-CN) is associated with the severity and mortality in patients with stroke, but the associations in different stroke subtypes remain unexplored. METHODS: We conducted an observational prospective cohort analysis on patients with ischemic stroke or transient ischemic attack enrolled in the Third China National Stroke Registry. We applied logistic models to assess the association of mtDNA-CN with functional outcome (modified Rankin Scale score, 3-6 versus 0-2) and Cox proportional hazard models to assess the association with stroke recurrence (treating mortality as a competing risk) and mortality during a 12-month follow-up, adjusting for sex, age, physical activity, National Institutes of Health Stroke Scale at admission, history of stroke and peripheral artery disease, small artery occlusion, and interleukin-6. Subgroup analyses stratified by age and stroke subtypes were conducted. RESULTS: The Third China National Stroke Registry enrolled 15 166 patients, of which 10 241 with whole-genome sequencing data were retained (mean age, 62.2 [SD, 11.2] years; 68.8% men). The associations between mtDNA-CN and poststroke/transient ischemic attack outcomes were specific to patients aged ≤65 years, with lower mtDNA-CN significantly associated with stroke recurrence in 12 months (subdistribution hazard ratio, 1.15 per SD lower mtDNA-CN [95% CI, 1.04-1.27]; P=5.2×10-3) and higher all-cause mortality in 3 months (hazard ratio, 2.19 [95% CI, 1.41-3.39]; P=5.0×10-4). Across subtypes, the associations of mtDNA-CN with stroke recurrence were specific to stroke of undetermined cause (subdistribution hazard ratio, 1.28 [95% CI, 1.11-1.48]; P=6.6×10-4). In particular, lower mtDNA-CN was associated with poorer functional outcomes in stroke of undetermined cause patients diagnosed with embolic stroke of undetermined source (odds ratio, 1.53 [95% CI, 1.20-1.94]; P=5.4×10-4), which remained significant after excluding patients with recurrent stroke (odds ratio, 1.49 [95% CI, 1.14-1.94]; P=3.0×10-3). CONCLUSIONS: Lower mtDNA-CN is associated with higher stroke recurrence rate and all-cause mortality, as well as poorer functional outcome at follow-up, among stroke of undetermined cause, embolic stroke of undetermined source, and younger patients.

Inflammatory marker profiles and in-hospital neurological deterioration in patients with acute minor ischemic stroke.

AIM: The aim of the study was to analyze the association between inflammatory marker profiles and in-hospital neurological deterioration (ND) in acute ischemic stroke (AIS) patients. METHODS: Data from patients with minor AIS from the Third China National Stroke Registry were analyzed. Inflammatory cytokine levels within 24 h of admission were measured. The primary outcome was in-hospital ND (an increase in National Institutes of Health Stroke Scale score ≥4 from admission to discharge). Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression models. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate incremental predictive values. RESULTS: A total of 4031 patients (1246 women, 30.9%) with a median age of 62 years were included. In-hospital ND occurred in 121 patients (3%). Each standard-deviation increase in interleukin (IL)-6 (OR, 1.17 [95% CI, 1.06-1.31]) and high-sensitivity C-reactive protein (hsCRP) (OR, 1.43 [95% CI, 1.24-1.66]) levels was associated with increased in-hospital ND risk. Incremental predictive values for adding IL-6 (IDI, 0.012; NRI, 0.329) but not hsCRP levels to the conventional risk factors were found. CONCLUSION: In minor AIS, hsCRP and IL-6 levels were associated with in-hospital ND, including IL-6 levels in prognostic models improved risk classification.

Assessment of Perfusion Volumes by a New Automated Software for Computed Tomography Perfusion.

INTRODUCTION: To compare the perfusion volumes assessed by a new automated CT perfusion (CTP) software iStroke with the circular singular value decomposition software RAPID and determine its predictive value for functional outcome in patients with acute ischaemic stroke (AIS) who underwent endovascular treatment (EVT). METHODS: Data on patients with AIS were collected from four hospitals in China. All patients received CTP followed by EVT with complete recanalisation within 24 hours of symptom onset. We evaluated the agreement of CTP measures between the two softwares by Spearman's rank correlation tests and kappa tests. Bland-Altman plots were used to evaluate the agreement of infarct core volume (ICV) on CTP and ground truth on diffusion-weighted imaging (DWI). Logistic regression models were used to test the association between ICV on these two softwares and functional outcomes. RESULTS: Among 326 patients, 228 had DWI examinations and 40 of them had infarct volume >70 mL. In all patients, the infarct core and hypoperfusion volumes on iStroke had a strong correlation with those on RAPID (ρ=0.68 and 0.66, respectively). The agreement of large infarct core (volume >70 mL) was substantial (kappa=0.73, p<0.001) between these two softwares. The ICV measured by iStroke and RAPID was significantly correlated with independent functional outcome at 90 days (p=0.009 and p<0.001, respectively). In patients with DWI examinations and those with an ICV >70 mL, the ICV of iStroke and RAPID was comparable on individual agreement with ground truth. CONCLUSION: The automatic CTP software iStroke is a reliable tool for assessing infarct core and mismatch volumes, making it clinically useful for selecting patients with AIS for acute reperfusion therapy in the extended time window.

Tibial transverse transport induces mobilization of endothelial progenitor cells to accelerate angiogenesis and ulcer wound healing through the VEGFA/CXCL12 pathway.

BACKGROUND: Tibial transverse transport (TTT) can promote the healing of chronic foot ulcers, but the specific cellular and molecular mechanisms by which TTT promotes wound healing remain unclear. METHODS: New Zealand White rabbits were selected to induce foot ulcer models. The treatment included unilateral TTT surgery and bilateral TTT surgery. Observation of tissue neovascularization structure by HE staining and CD31 immunofluorescence detection. Collagen fiber formation was detected through the Masson staining. The mobilization of endothelial progenitor cell (EPCs) were analyzed by VEGFR2 immunofluorescence detection and flow cytometry detection of the number of VEGFR2/Tie-2-positive cells in peripheral blood. ELISA and qPCR assay were performed to detect VEGFA and CXCL12 levels. RESULTS: The complete healing time of ulcer surfaces in sham, unilateral and bilateral TTT groups was about 22 days, 17 days and 13 days, respectively. TTT treatment significantly increased the deposition of granulation tissue and epithelialization of wounds. It also led to an increase in collagen fiber content and the level of the microvascular marker CD31. Furthermore, TTT treatment upregulated the levels of VEGFA and CXCL12 in peripheral blood and wound tissues, as well as increased the expression of VEGFR2 in wound tissues and the proportion of VEGFR2/Tie-2 in peripheral blood. Moreover, these effects of TTT treatment in the bilateral group was more significant than that in the unilateral group. CONCLUSIONS: TTT may facilitate wound fibroblasts to release VEGFA and CXCL12, causing EPC mobilization, thus promoting angiogenesis and ulcer wound healing.