Association between Triglyceride-Glucose Index and Early Neurological Outcomes after Thrombolysis in Patients with Acute Ischemic Stroke.

BACKGROUND: The triglyceride-glucose (TyG) index is a novel biomarker of insulin resistance which might plausibly influence endogenous fibrinolysis and thus early neurological outcomes in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis using recombinant tissue-plasminogen activator. METHODS: We included consecutive AIS patients within 4.5 h of symptom onset undergoing intravenous thrombolysis between January 2015 and June 2022 in this multi-center retrospective observational study. Our primary outcome was early neurological deterioration (END), defined as ≥2 (END2) or ≥ 4 (END4) National Institutes of Health Stroke Scale (NIHSS) score worsening compared to the initial NIHSS score within 24 h of intravenous thrombolysis. Our secondary outcome was early neurological improvement (ENI), defined as a lower NIHSS score at discharge. TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. We evaluated the association of END and ENI with TyG index using a logistic regression model. RESULTS: A total of 676 patients with AIS were evaluated. The median age was 68 (Interquartile range, IQR (60-76) years old), and 432 (63.9%) were males. A total of 89 (13.2%) patients developed END2, 61 (9.0%) patients developed END4, and 492 (72.7%) experienced ENI. In multivariable logistic regression analysis, after adjustment for confounding factors, TyG index was significantly associated with increased risks of END2 (categorical variable, vs. lowest tertile, medium tertile odds ratio [OR] 1.05, 95% confidence interval, CI 0.54-2.02, highest tertile OR 2.94, 95%CI 1.64-5.27, overall p < 0.001) and END4 (categorical variable, vs. lowest tertile, medium tertile OR 1.21, 95%CI 0.54-2.74, highest tertile OR 3.80, 95%CI 1.85-7.79, overall p < 0.001), and a lower probability of ENI (categorical variable, vs. lowest tertile, medium tertile OR 1.00, 95%CI 0.63-1.58, highest tertile OR 0.59, 95%CI 0.38-0.93, overall p = 0.022). CONCLUSIONS: Increasing TyG index was associated with a higher risk of END and a lower probability of ENI in patients with acute ischemic stroke treated with intravenous thrombolysis.

Treadmill exercise exerts a synergistic effect with bone marrow mesenchymal stem cell-derived exosomes on neuronal apoptosis and synaptic-axonal remodeling.

Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia. However, whether there is a synergistic effect between the two remains unclear. In this study, we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes (MSC-exos) via the tail vein and underwent 14 successive days of treadmill exercise. Neurological assessment, histopathology, and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume, evident synaptic formation and axonal regeneration, and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment. These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone. Mechanistically, further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling. These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment, which may be related to activation of the JNK1/c-Jun signaling pathway. This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.

Determinants for a low dose of alteplase and its relationship to a lower intracerebral bleeding risk in acute ischemic stroke.

Background: Factors for the utilization of intravenous thrombolysis with a low-dose of alteplase (0.6mg/kg) and whether the low-dose of alteplase could reduce the risk of intracerebral bleeding in acute ischemic stroke (AIS) remains uncertain. Aims: We aimed to investigate determinants for the utilization of intravenous thrombolysis with a low-dose of alteplase. We further assessed the association between the low-dose of alteplase and the intracerebral bleeding risk in AIS patients. Method: We included AIS patients who received intravenous thrombolysis using alteplase in this multicenter retrospective observational study. We investigated the association between baseline characteristics and the utilization of a low-dose of alteplase to identify determinants. We assessed the association of the low-dose of alteplase with the risk of symptomatic intracranial hemorrhage (sICH) using a multivariable logistic regression model. We further compared the rate of sICH and any ICH in patients in the low-dose group to those in the standard-dose group, using propensity score-matching data. Results: A total of 506 AIS patients were included in this study. The mean age was 67 (interquartile range [IQR] 59-75), and 178 (35.2%) were women. A total of 96 patients were treated with the low-dose. Age (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 1.00 -1.04, p = 0.042), having a previous ischemic stroke (adjusted OR 2.01, 95%CI 1.11 - 3.64 p = 0.021) and increasing baseline systolic blood pressure (adjusted OR 1.12, 95%CI 1.00 - 1.26, p = 0.049) were determinants for the utilization of the low-dose. Multivariable logistic regression analysis showed that the low-dose was significantly associated with a reduced risk of sICH (adjusted OR 0.13, 95%CI 0.03 - 0.62, p = 0.01). Propensity score analysis showed that the rate of sICH was significantly lower in the low-dose group compared to standard-dose group (2 [2.3%] vs 10 [11.4%], p = 0.032). There was no significant difference in the rate of any ICH between two groups (14 [15.9%] vs 18 [20.5%], p = 0.434). Conclusions: Patients with increasing age, a higher baseline systolic blood pressure, and previous ischemic stroke were at a higher odd of receiving a low-dose of alteplase. The low-dose was associated with a lower risk of developing symptomatic intracranial hemorrhage.

Total Cerebral Small Vessel Disease Score and Cerebral Bleeding Risk in Patients With Acute Stroke Treated With Intravenous Thrombolysis.

Objective: The aim of this study was to investigate the association of total cerebral small vessel disease (cSVD) score with the risk of intracerebral hemorrhage (ICH) in patients with acute ischemic stroke who received intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA). Methods: We retrospectively reviewed clinical data from two stroke registries of patients with acute ischemic stroke treated with IVT. We assessed the baseline magnetic resonance (MR) visible cSVD markers and total cSVD score (ranging from 0 to 4) between patients with and without ICH after IVT. Logistic regression analysis was used to determine the association of total cSVD score with the risk of ICH after IVT, adjusted for cofounders selected by least absolute shrinkage and selection operator (LASSO). We additionally performed an E-value analysis to fully explain away a specific exposure-outcome association. Receiver operating characteristic (ROC) curve analysis was used to quantify the predictive potential of the total cSVD score for any ICH after IVT. Results: Among 271 eligible patients, 55 (20.3%) patients experienced any ICH, 16 (5.9%) patients experienced a symptomatic ICH (sICH), and 5 (1.85%) patients had remote intracranial parenchymal hemorrhage (rPH). Logistic regression analysis showed that the risk of any ICH increased with increasing cSVD score [per unit increase, adjusted odds ratio (OR) 2.03, 95% CI 1.22-3.41, P = 0.007]. Sensitivity analyses using E-value revealed that it would need moderately robust unobserved confounding to render the exposure-outcome (cSVD-any ICH) association null. ROC analysis showed that compared with the National Institutes of Health Stroke Scale (NIHSS) score alone, a combination of cSVD and NIHSS score had a larger area under the curve for any ICH (0.811, 95% CI 0.756-0.866 vs. 0.784, 95% CI 0.723-0.846, P = 0.0004). Conclusion: The total cSVD score is associated with an increased risk of any ICH after IVT and improves prediction for any ICH compared with NIHSS alone.

Phase optimization algorithm for 3D particle localization with large axial depth.

We propose an optimization algorithm based on Fresnel approximation (FA) imaging to optimize an extended-axial-depth point spread function (PSF) for 3D particle localization. The transfer function efficiency of the PSF is improved by repeatedly imposing constraints in the object plane, the spatial domain, and the Fourier domain. During the iterative calculation, the effective photon number or Cramer-Rao lower bound is used as the termination condition of the iteration. The algorithm allows flexible adjustment of the peak intensity ratio of the two main lobes. Moreover, the transfer function efficiency can be balanced by increasing the weight of the modulation function of the expected PSF at each axial position. The twin-Airy (TA) PSF optimized by the FA optimization algorithm does not require complex post-processing, whereas post-processing is an essential step for the unoptimized TA-PSF. The optimization algorithm is significant for extended-axial-depth PSFs used for 3D particle localization, as it improves localization precision and temporal resolution.

Splicing exponential point spread function design for localization of nanoparticles.

We propose a point spread function for three-dimensional localization of nanoparticles. The axial detection range of the point spread function can be simply changed by adjusting the design parameters. In addition, the spatial extent of the point spread function can also be changed by adjusting the design parameters, which is an advantage other point spread functions do not have. We used our point spread functions and the existing point spread functions for dense multi-particle imaging, which proved the advantage that the point spread function with a smaller spatial extent we designed can effectively reduce the overlap between the point spread functions. The three-dimensional process of the fluorescent microsphere penetrating HT-22 cell membrane was successfully recorded, which verified the effectiveness of this method.

Particles 3D tracking with large axial depth by using the 2π-DH-PSF.

We propose a 2π-double-helix point spread function (2π-DH-PSF) using the Fresnel zone approach that can rotate 2π rad. When 16 Fresnel zones are used, the particles can be tracked in the axial range of 10 µm in a 100× microscopy imaging system (NA=1.4, λ=514nm). We measured the diffusion coefficient of nanospheres in different concentrations of glycerol with the 2π-DH-PSF, and the error between the measured results and theoretical value was within 10%, indicating the superior performance of 2π-DH-PSF in 3D localization imaging of nanoparticles. When combined with the defocus phase, the rotation angle can reach 4π rad, four times that of the conventional DH-PSF.

Three-dimensional diffusion coefficient measurement by a large depth-of-field rotating point spread function.

A prominent challenge in single-molecule localization microscopy is the real-time, fast, and accurate localization of nano-objects moving in three-dimensional (3D) samples. A well-established method for 3D single-molecule localization is the double-helix pointspread-function (DH-PSF) engineering, which uses additional optical elements to make the PSF exhibit different rotation angles with different nanoparticle depths. However, the compact main lobe size, effective detection depth, and precise conversion between rotation angle and depth are necessary, posing challenges to the DH-PSF generation method. Here we generate a more compact DH-PSF using Fresnel-zone-based spiral phases, and the pure phase mask achieves high transmission efficiency. The final generated DH-PSFs have a linear rotation rate at each axial position, showing a more accurate rotation angle and depth conversion. The Cramer-Rao lower limit calculation results show that the axial depth of DH-PSF extends to ∼11µm with an axial localization precision of ∼45nm at 3000 photons and average background noise of 15. We measured the diffusion coefficient of nanospheres in different concentrations of glycerol using the generated DH-PSF. The measured results are within 6% error from the theoretical values, indicating the superior performance of the DH-PSF for nanoparticle diffusion coefficient measurements.