Artificial Intelligence-Assisted Multiparameter Size Discrimination of Silver Nanoparticles through Electrochemical Collision.

Single particle collision is an important tool for size analysis at the individual particle level; however, due to complex dynamic behaviors of nanoparticles on the surface of an electrode, the accuracy of size discrimination is limited. A silver (Ag) nanoparticle (NP) was chosen as the research target, and the dynamic behavior of Ag NPs was simplified by enhancing adsorption between Ag NP and Au ultramicroelectrode (UME) in alkaline media. Immediately after, accurate dynamic and thermodynamic information on single Ag NP was accurately extracted from collision events, including current intensity, transferred charge, and duration time. On the basis that there were differences between parameters of different-sized Ag NPs, multiparameter size discrimination was proposed, which improved the accuracy compared to single-parameter discrimination. More intriguingly, multiparameter analysis was combined with artificial intelligence, a tool adept at processing multidimensional data, for the first time. Finally, artificial intelligence-assisted multiparameter size discrimination was successfully used to intelligently distinguish mixed Ag NPs, with an optimal accuracy of more than 95%. To sum up, the artificial intelligence-assisted multiparameter method showed an excellent ability to quickly achieve the most accurate size discrimination of nanoparticles at the level of individual particle and provide an effective guidance for the application of nanoparticles.

Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 􀁐g/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 􀁐g/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

Peri-procedural variables and outcomes of long-period hemodynamic instability after carotid artery angioplasty and stenting.

OBJECTIVES: The aim of this study is to identify the peri-procedural risk factors and outcomes of hemodynamic instability (HI) after carotid artery stenting (CAS). METHODS: A single-center, retrospective study was performed in 168 patients who underwent CAS procedure between September 2017 and September 2020. The presence of HI, as defined by hypertension (systolic blood pressure >160 mmHg), hypotension (systolic blood pressure <90 mmHg), and/or bradycardia (heart rate <60 bpm), was recorded. Long-period HI was defined as persistent HI lasting more than 24 h. Patient demographics, comorbidities, peri-procedural variables, and risk factors were recorded. Clinical outcomes including cerebral hyperperfusion syndrome, hemorrhage, transient ischemic attack (TIA), stroke, myocardial infarction, and mortality within 30 days of the procedure were evaluated. Logistic regression was used to analyze the independent risk factors of long-period HI following CAS. RESULTS: Among 168 patients (mean age, 68.2 ± 8.3 years; 81.5% male), the frequency of post-procedural long-period HI was noted in 42 patients (25.0%). Male was prone to experience HI (odds ratio, 9.156, p = 0.021). Aggressive inflation pressure (>7 atm) and 5 mm balloon for pre-dilatation were risk factors of long-period HI (OR, 7.372, p = 0.035; OR, 3.527, p = 0.023). Intraoperative peak blood pressure and larger-sized stents remained independent predictors for the development of HI (OR, 1.043, p = 0.027, and OR, 1.973, p = 0.015). Patients with prolonged HI were more likely to suffer TIA and stroke compared to other patients and significant difference was found in the occurrence of TIA (p < 0.05). Non-significance was found in mortality rate and other outcomes. CONCLUSIONS: CAS-induced HI occurs in a considerable percentage while several peri-procedural variables are determined as independent predictors to develop long-period HI. Patients with prolonged HI are associated with increased risk of neurologic events and thus standardized intervention as well as management of long-period HI are of critical importance during clinical process.

Predictors of Early Neurological Deterioration Occurring within 24 h in Acute Ischemic Stroke following Reperfusion Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Early neurological deterioration (END), generally defined as the increment of National Institutes of Health Stroke Scale (NIHSS) score ≥4 within 24 hours, lead to poor clinical outcome in acute ischemic stroke (AIS) patients receiving reperfusion therapies including intravenous thrombolysis (IVT) and/or endovascular treatment (EVT). This systematic review and meta-analysis aimed to explore multiple predictors of END following reperfusion therapies. METHODS: We searched PubMed, Web of Science and EBSCO for all studies on END in AIS patients receiving IVT and/or EVT published between January 2000 and December 2022. A random-effects meta-analysis was conducted and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of each included studies was assessed by calculating a total score according to the STROBE or CONSORT criteria. Publication bias and heterogeneity were also evaluated using the Eggers/Peters test, funnel plots and sensitivity analysis. RESULTS: A total of 29 studies involving 65,960 AIS patients were included. The quality of evidence is moderate to high, and all studies have no publication bias. The overall incidence of END occurring after reperfusion therapy in AIS patients was 14% ((95% confidence intervals (CI), 12%-15%)). Age, systolic blood pressure (SBP), glucose levels at admission, the onset to treatment time (OTT), hypertension, diabetes mellitus, arterial fibrillation, and internal cerebral artery occlusion were significantly associated with END following reperfusion therapy. CONCLUSIONS: Numerous factors are associated with END occurrence in AIS patients receiving reperfusion therapy. Management of the risk factors of END may improve the functional outcome after reperfusion treatment.

Safety and efficacy of endovascular recanalization in patients with mild anterior stroke due to large-vessel occlusion exceeding 24 hours.

BACKGROUND: Endovascular recanalization (ER) has demonstrated efficacy as a treatment modality for patients presenting with acute ischemic stroke (AIS) caused by large-vessel occlusion (LVO) within a 24-hour timeframe. Nevertheless, the safety and effectiveness of ER in patients with a time of onset exceeding 24 h remain uncertain. OBJECTIVE: To evaluate the safety and efficacy of ER treatment for mild ischemic stroke beyond 24-h from symptom onset. METHODS: A retrospectively maintained database of mild AIS due to LVO from March2018 to September 2022 at a comprehensive stroke center was screened.Patients received ER or standard medical therapies (SMT) for anterior circulation AIS due to LVO > 24-h were selected. RESULTS: We included 47 LVO patients with mild AIS beyond 24-h who suffered neurological deterioration (ND). 34 of these patients underwent ER, the other 13 received SMT. The technical success rate of recanalization was 82.4% (28/34). Patients received ER had significantly lower NIHSS score at discharge and 90-day mRS score (p = 0.028, p = 0.037, respectively) compared to SMT. In addition, they had significantly lower 90-day recurrence of ischemic stroke and lower incidence of moderate-severe stroke (with a NIHSS score at least 5) (p = 0.037, p = 0.033). There were 4 patients (11.7%) had perioperative complications, and no symptomatic intracranial hemorrhage occurred. CONCLUSION: ER treatment for mild AIS due to LVO encountered ND was generally safe and effective, even beyond 24-h, and resulted in a good prognosis and lower 90-day recurrence compared to SMT.

ER for mild anterior stroke might be safe and feasible, even exceeding 24-h;The proposed protocol could be used for individualized treatment decision making;Modelling for heterogeneity of treatment effect.

Improving cancer immunotherapy by rationally combining oncolytic virus with modulators targeting key signaling pathways.

Oncolytic viruses (OVs) represent a new class of multi-modal immunotherapies for cancer, with OV-elicited antitumor immunity being key to their overall therapeutic efficacy. Currently, the clinical effectiveness of OV as monotherapy remains limited, and thus investigators have been exploring various combinations with other anti-cancer agents and demonstrated improved therapeutic efficacy. As cancer cells have evolved to alter key signaling pathways for enhanced cell proliferation, cancer progression and metastasis, these cellular and molecular changes offer promising targets for rational cancer therapy design. In this regard, key molecules in relevant signaling pathways for cancer cells or/and immune cells, such as EGFR-KRAS (e.g., KRASG12C), PI3K-AKT-mTOR, ERK-MEK, JAK-STAT, p53, PD-1-PD-L1, and epigenetic, or immune pathways (e.g., histone deacetylases, cGAS-STING) are currently under investigation and have the potential to synergize with OV to modulate the immune milieu of the tumor microenvironment (TME), thereby improving and sustaining antitumor immunity. As many small molecule modulators of these signaling pathways have been developed and have shown strong therapeutic potential, here we review key findings related to both OV-mediated immunotherapy and the utility of small molecule modulators of signaling pathways in immuno-oncology. Then, we focus on discussion of the rationales and potential strategies for combining OV with selected modulators targeting key cellular signaling pathways in cancer or/and immune cells to modulate the TME and enhance antitumor immunity and therapeutic efficacy. Finally, we provide perspectives and viewpoints on the application of novel experimental systems and technologies that can propel this exciting branch of medicine into a bright future.

Practical value of three-dimensional high resolution magnetic resonance Vessel Wall imaging in identifying suspicious intracranial vertebrobasilar dissecting aneurysms.

BACKGROUND: Direct evidence of intimal flaps, double lumen and intramural haematomas (IMH) is difficult to detect on conventional angiography in most intracranial vertebrobasilar dissecting aneurysms (VBDAs). Our purpose was to assess the value of three-dimensional high-resolution magnetic resonance vessel wall imaging (3D HRMR VWI) for identifying VBDAs. METHODS: Between August 2013 and January 2016, consecutive patients with suspicious VBDAs were prospectively enrolled to undergo catheter angiography and VWI (pre- and post-contrast). The lesion was diagnosed as definite VBDA when presenting direct signs of dissection; as possible when only presenting indirect signs; and as segmental ectasia when there was local dilation and wall thickness similar to adjacent normal artery's without mural thrombosis. RESULTS: Twenty-one patients with 27 lesions suspicious for VBDAs were finally included. Based on findings of VWI and catheter angiography, definite VBDA was diagnosed in 25 and 7 lesions (92.6%, vs 25.9%, p <  0.001), respectively; possible VBDA in 0 and 20 (0 vs 74.1%), respectively; and segmental ectasia in 2 and 0 (7.4% vs 0%), respectively. On VWI and catheter angiography, intimal flap was detected in 21 and 7 lesions (77.8% vs 25.9%, p = 0.001), respectively; double lumen sign in 18 and 7 (66.7% vs 25.9%, p = 0.003), respectively; and IMH sign in 14 and 0 (51.9% vs 0), respectively. CONCLUSIONS: 3D HRMR VWI could detect direct dissection signs more frequently than catheter angiography. This may help obtain definite diagnosis of intracranial VBDAs, and allow accurate differentiation between dissecting aneurysm and segmental ectasia as well. Further prospective study with larger sample was required to investigate the superiority of HRMR VWI for definite diagnosis of intracranial VBDAs than catheter angiography.

Molecular mechanism of long-term neuroprotective effects of gradual flow restoration on cerebral ischemia reperfusion injury in MCAO rats.

BACKGROUND AND PURPOSE: Ischemia-reperfusion injuries (IRIs) can aggravate the condition of some patients with acute occlusion of major intracranial artery (AOMIA) who received endovascular thrombectomy. Here, we provided data confirming the association of Repressor Element-1 Silencing Transcription factor (REST) with the long-term neuroprotective effect of the middle cerebral artery occlusion (MCAO) rats underwent Gradual Flow Restoration (GFR). METHODS: Long term neuroprotective effects of GFR intervention were evaluated on MCAO rats model after 3d and 7d reperfusion. The neurological deficit score and TTC staining were performed to evaluate the degree of brain damage in GFR and other interventions at different time. Differentially expressed genes related to cerebral ischemia reperfusion injury (CIRI) were initially screened and identified using GSE32529 microarray analysis. REST protein expression in rat brain cortex infarction was detected by Western blot analysis. RESULTS: MCAO rats intervened with GFR exhibited reduced neurological deficit (P < 0.05) and alleviated brain infarction volume (P < 0.01). The REST gene with up-regulated expression and its downstream genes with down-regulated expression were screened by Microarray analysis. The brain cortex infarction in MCAO rats produced high levels of REST expression. The GFR intervention inhibited REST expression, and alleviated brain injury on MCAO rats. CONCLUSION: Our results demonstrated that GFR intervention plays a long-term neuroprotective role and reduces brain edema and damage at reperfusion, possibly by inhibiting REST expression.

Interactive effect of susceptibility-diffusion mismatch and recanalization status on clinical outcome in large vessel occlusion stroke.

OBJECTIVE: To investigate the interactive effect of susceptibility-diffusion mismatch and recanalization status on clinical outcome in patients with acute ischemic stroke due to large vessel occlusion. METHODS: In this prospective study, consecutive ischemic stroke patients admitted within 24 h from symptom onset underwent emergency multimodal MRI at admission, including diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and time-of-flight magnetic resonance angiography (TOF-MRA). Patients with large vessel occlusion within the anterior circulation were recruited. Follow-up MRI was performed within 24 h after recanalization therapy (intravenous thrombolysis, endovascular therapy, or both). Multivariable logistic regression analysis was performed to estimate the interaction between SWI-DWI mismatch score and recanalization status on clinical outcome. RESULTS: A total of 90 patients were enrolled. A multiplicative interaction between SWI-DWI mismatch score and recanalization status on clinical outcome was observed (P=0.037). The interaction term "SWI-DWI mismatch score × successful recanalization" was significantly associated with favorable outcome (modified Rankin Scale score of 0-2 at 90 days; adjusted odds ratio [aOR], 2.162; 95% confidence interval [CI], 1.046-4.468). Stratified analysis showed that the likelihood of favorable outcome increased with the increase of SWI-DWI mismatch score in the successful recanalization group (OR, 2.140; 95% CI, 1.376-3.326), while there was no significant relationship between SWI-DWI mismatch score and clinical outcome in the unsuccessful recanalization group (OR, 1.212; 95% CI, 0.933-1.574). CONCLUSIONS: The effects of SWI-DWI mismatch and recanalization status on clinical outcome were realized through their interaction. In anterior circulation stroke due to large vessel occlusion, patients with both high SWI-DWI mismatch scores and successful recanalization were more likely to achieve a favorable outcome, while patients with unsuccessful recanalization, or with successful recanalization but low SWI-DWI mismatch scores, were less likely to have a good prognosis.

Association of GPIa and COX-2 gene polymorphism with aspirin resistance.

OBJECTIVE: This study aimed to explore the association between GPIa, COX-2 gene polymorphisms and aspirin resistance in the ischemic stroke patients from the southern part of Jiangsu province. METHODS: In all, 97 patients with acute ischemic stroke were enrolled in the study. GPIa gene polymorphism at 807C>T (rsl126643) locus and COX-2 gene polymorphism at -765G>C (rs20417) locus were genotyped by PCR pyrosequencing technology. Patients were divided into the aspirin sensitivity (AS) group and aspirin resistance (AR) group according to the platelet aggregation rate. The relationship between the two gene polymorphisms and aspirin resistance was investigated and analyzed. RESULTS: The distribution of the genotype (CC, CT, TT, CT + TT, and CC) and the frequency of allele T of GPIa gene at 807C>T locus were significantly different in AS and AR groups in female patients (P < .05). Logistic regression analysis showed that the genotype of CT+TT at 807C>T locus was significantly correlated with AR after adjustment for relative factors (P = .047, OR = 4.856, 95% CI: 1.020-23.108). There were no significant differences in the genotype distribution and allele frequency of the COX-2 gene -765G>C site between two groups (P > .05). CONCLUSION: GPIa gene polymorphism at 807C>T locus was associated with AR in Chinese Han females, and the expression of allele T increased the incidence of AR. The gene polymorphism of COX-2 gene at -765G>C locus was not significantly correlated with AR.

Evaluation of basilar artery atherosclerotic plaque distribution by 3D MR vessel wall imaging.

PURPOSE: Basilar artery (BA) atherosclerosis is an important cause of perforator stroke in the brainstem due to plaque involvement of the perforator ostia in BA dorsal or lateral walls. Therefore, to acquire information on plaque distribution is important to better understand and prevent the perforator stroke. This study aimed to comprehensively evaluate BA plaque distribution with 3D magnetic resonance imaging (MRI) vessel wall imaging. MATERIALS AND METHODS: Consecutive patients with cerebrovascular symptoms and stenosis or irregular luminal surface of BA were recruited and underwent BA 3D proton density-weighted volume isotropic turbo spin echo acquisition (VISTA) imaging at 3T. The cross-sectional and longitudinal distribution of BA plaque were analyzed with a custom-developed tool. RESULTS: In all, 85 BA plaques were detected in 61 recruited patients. For cross-sectional distribution, the prevalence of plaque involvement in the ventral, left, dorsal, and right quadrant of BA wall was 74.1%, 70.6%, 67.1%, and 62.4%, respectively. Of the 85 plaques, 17.7% involved one quadrant and 82.3% involved two or more quadrants. The most severe plaque region was more commonly situated at lateral walls (66.1%) as compared to ventral (23.2%, P < 0.001) and dorsal walls (10.6%, P < 0.001). Longitudinally, plaques were more frequently found to occur at BA segment distal than proximal to anterior inferior cerebellar artery (AICA) (63.5% vs. 36.5%). CONCLUSION: Taking advantage of 3D MR vessel wall imaging, BA plaques were found to more likely affect lateral walls and form in BA distal to AICA, where most perforators originate, suggesting that it might be useful to characterize BA plaque distribution before aggressive treatment for prevention of perforator stroke. J. Magn. Reson. Imaging 2016;44:1592-1599.

Wall thickening pattern in atherosclerotic basilar artery stenosis.

Our aim was to investigate wall thickening (WT) pattern of atherosclerotic basilar artery stenosis with three-dimensional volumetric isotropic turbo spin echo acquisition (3D VISTA), and the relationship with clinical characteristics. Twenty consecutive patients with atherosclerotic basilar artery stenosis were prospectively enrolled. All cross-sectional slices on VISTA images of basilar arteries were assessed, and classified as eccentric or concentric WT. Clinical characteristics and degree of stenosis were compared between the patients with different wall WT pattern. Wall abnormalities were identified in 568 cross-sectional slices in basilar arteries of 20 patients including eccentric WT in 497 (87.5 %) slices, and concentric WT in 71 (12.5 %) slices. In 11 of 20 patients, all the cross-sectional slices (293 slices) showed eccentric WT. In 9 of 20 patients, the cross-sectional slices (275 slices) showed both eccentric WT (204 slices, 74.2 %) and concentric WT (71 slices, 25.8 %). No lesion showed only concentric WT. At the slices of maximum luminal narrowing sites, only one patient showed concentric WT. Symptomatic stenosis was more common in the patients with mixed WT (eccentric and concentric), compared to patients with only eccentric WT (100 vs 54.5 %, p = 0.038). Atherosclerotic basilar artery stenosis could show both eccentric and concentric WT based on each slice analysis. Concentric WT was found in near half of the patients, but tended to locate in minimal slices. No lesion was entirely concentric. Lesions with mixed WT (concentric and eccentric) might represent advanced atherosclerosis with high risk of ischemic event.

Noninvasive visualization of the basilar artery wall and branch ostia with high-resolution three-dimensional black-blood sequence at 3 tesla.

PURPOSE: To evaluate the usefulness of three-dimensional (3D) MR black-blood sequence flow-dephasing-prepared fast spoiled gradient recalled echo (FDP-FSPGR) in screening the basilar artery (BA) wall and the ostia of the adjacent branch arteries. MATERIALS AND METHODS: Twenty-one patients with BA stenosis >50% on digital subtraction angiography (DSA) were imaged. Three-dimensional FDP-FSPGR images were acquired using a flow-dephasing-prepared segmented technique, including two spin echoes to overcome the inhomogeneity of the radiofrequency field. Precontrast and postcontrast 3D FDP-FSPGR sequences were performed. RESULTS: The wall of the BA could be visualized in 20 patients with good contrast, and 82 ostia of the adjacent branch arteries were identified on 3D FDP-FSPGR images. Compared with DSA, the accuracy of it was 0.94 (95% confidence interval [CI], 0.89 to 0.99) for reader 1 and 0.92 (95% CI, 0.86 to 0.98) for reader 2, with strong agreement between the two readers (κ = 0.82). BA plaque enhancement was noted in 16 of the 20 patients after contrast administration. CONCLUSION: The 3D FDP-FSPGR can be used for high-spatial-resolution demonstration and large coverage of the BA wall and the ostia of the adjacent branch arteries. This sequence will make it possible to evaluate therapeutic effects in clinical studies.

Requirement for integrin-linked kinase in neural crest migration and differentiation and outflow tract morphogenesis.

BACKGROUND: Neural crest defects lead to congenital heart disease involving outflow tract malformation. Integrin-linked-kinase (ILK) plays important roles in multiple cellular processes and embryogenesis. ILK is expressed in the neural crest, but its role in neural crest and outflow tract morphogenesis remains unknown. RESULTS: We ablated ILK specifically in the neural crest using the Wnt1-Cre transgene. ILK ablation resulted in abnormal migration and overpopulation of neural crest cells in the pharyngeal arches and outflow tract and a significant reduction in the expression of neural cell adhesion molecule (NCAM) and extracellular matrix components. ILK mutant embryos exhibited an enlarged common arterial trunk and ventricular septal defect. Reduced smooth muscle differentiation, but increased ossification and neurogenesis/innervation were observed in ILK mutant outflow tract that may partly be due to reduced transforming growth factor ß2 (TGFß2) but increased bone morphogenetic protein (BMP) signaling. Consistent with these observations, microarray analysis of fluorescence-activated cell sorting (FACS)-sorted neural crest cells revealed reduced expression of genes associated with muscle differentiation, but increased expression of genes of neurogenesis and osteogenesis. CONCLUSIONS: Our results demonstrate that ILK plays essential roles in neural crest and outflow tract development by mediating complex crosstalk between cell matrix and multiple signaling pathways. Changes in these pathways may collectively result in the unique neural crest and outflow tract phenotypes observed in ILK mutants.

[First domestic case of intracranial aneurysm parent artery remodeling hybrid surgery].

OBJECTIVE: To explore new treatment modalities for complex intracranial aneurysms. METHODS: Under general anesthesia, intracranial aneurysm parent artery remodeling surgery was performed along with repeated immediate intraoperative cerebral angiogram to verify the effect of revascularization and therefore adjust the operation plan accordingly. RESULTS: Aneurysm was successfully clipped without injuries of vascular branches. Prognosis was excellent. CONCLUSION: Complex hybrid surgery is an ideal option for parent artery remodeling of complicated intracranial aneurysms.

Application of a nomogram model for the prediction of 90-day poor outcomes following mechanical thrombectomy in patients with acute anterior circulation large-vessel occlusion.

Background: The past decade has witnessed advancements in mechanical thrombectomy (MT) for acute large-vessel occlusions (LVOs). However, only approximately half of the patients with LVO undergoing MT show the best/independent 90-day favorable outcome. This study aimed to develop a nomogram for predicting 90-day poor outcomes in patients with LVO treated with MT. Methods: A total of 187 patients who received MT were retrospectively analyzed. Factors associated with 90-day poor outcomes (defined as mRS of 4-6) were determined by univariate and multivariate logistic regression analyzes. One best-fit nomogram was established to predict the risk of a 90-day poor outcome, and a concordance index was utilized to evaluate the performance of the model. Additionally, 145 patients from a single stroke center were retrospectively recruited as the validation cohort to test the newly established nomogram. Results: The overall incidence of 90-day poor outcomes was 45.16%, affecting 84 of 186 patients in the training set. Moreover, five variables, namely, age (odds ratio [OR]: 1.049, 95% CI [1.016-1.083]; p = 0.003), glucose level (OR: 1.163, 95% CI [1.038-1.303]; p = 0.009), baseline National Institute of Health Stroke Scale (NIHSS) score (OR: 1.066, 95% CI [0.995-1.142]; p = 0.069), unsuccessful recanalization (defined as a TICI grade of 0 to 2a) (OR: 3.730, 95% CI [1.688-8.245]; p = 0.001), and early neurological deterioration (END, defined as an increase of ≥4 points between the baseline NIHSS score and the NIHSS score at 24 h after MT) (OR: 3.383, 95% CI [1.411-8.106]; p = 0.006), were included in the nomogram to predict the potential risk of poor outcomes at 90 days following MT in LVO patients, with a C-index of 0.763 (0.693-0.832) in the training set and 0.804 (0.719-0.889) in the validation set. Conclusion: The proposed nomogram provided clinical evidence for the effective control of these risk factors before or during the process of MT surgery in LVO patients.

A novel nomogram to predict futile recanalization in patients with acute ischemic stroke undergoing mechanical thrombectomy.

Background and objective: Futile recanalization (FR) is defined as patients with acute ischemic stroke (AIS) due to large vessel occlusion who still exhibits functional dependence although undergoing successful mechanical thrombectomy (MT). We aimed to develop and validate a simple nomogram for predicting the probability of FR after MT treatment in AIS patients. Methods: Clinical data of AIS patients in the Jrecan clinical trial in China from March 2018 to June 2019 were collected as the derivation set (n = 162). Meanwhile, clinical data of AIS patients who underwent MT in Baotou Central Hospital and Ningbo No.2 Hospital from 2019 to 2021 were collected as the validation set (n = 170). Multivariate logistic regression analysis was performed for all variables that had p < 0.2 in the univariate analysis in the derivation set. The independent risk factors of FR were further screened out and a nomogram was constructed. The performance of the nomogram was analyzed in the derivation and validation set using C-index, calibration plots, and decision curves. Results: No significant difference in FR rate was detected between the derivation set and the validation set [88/162 (54.32%) and 82/170 (48.23%), p = 0.267]. Multivariate logistic regression analysis showed that age ≥ 65 years old (OR = 2.096, 95%CI 1.024-4.289, p = 0.043), systolic blood pressure (SBP) ≥ 180 mmHg (OR = 5.624, 95%CI 1.141-27.717, p = 0.034), onset to recanalization time (OTR) ≥ 453 min (OR = 2.759, 95%CI 1.323-5.754, p = 0.007), 24 h intracerebral hemorrhage (ICH; OR = 4.029, 95%CI 1.844 ~ 8.803, p < 0.001) were independent risk factors for FR. The C-index of the nomogram of the derivation set and the verification set were 0.739 (95%CI 0.662~0.816) and 0.703 (95%CI 0.621~0.785), respectively. Conclusion: The nomogram composed of age, SBP, OTR, and 24 h ICH can effectively predict the probability of FR after MT in AIS patients.

Higher risk of recurrent ischemic events in patients with intracranial in-stent restenosis.

BACKGROUND AND PURPOSE: Reliable data concerning prognosis of patients with intracranial in-stent restenosis (ISR) is lacking. We prospectively studied long-term outcomes of patients with and without a catheter angiography-verified ISR. METHODS: Between September 2001 and May 2009, 540 consecutive patients with symptomatic intracranial atherosclerosis received stenting treatment at our institute. Of them, 226 patients with 233 stented arteries had catheter angiography follow-up after stenting and were enrolled into this study. They were clinically followed up until the end of December 2011. Primary end point was ischemic stroke or transient ischemic attack in the territory of the stented artery after the catheter angiography follow-up. ISR was defined as a catheter angiography-verified stenosis of ≥50% within or immediately adjacent (within range of 3 mm) to the implanted stent. RESULTS: During a mean follow-up of 38.9 months, 27 (11.6%, 27/233) primary end point events were recorded. The risk of primary end point in ISR group was higher compared with non-ISR group (21.1% [12/57] versus 8.5% [15/176]; hazard ratio, 2.94; 95% confidence interval, 1.37-6.30; P=0.005). Multivariable analysis showed that the ISR was an independent risk factor for the primary end point (hazard ratio, 2.79; 95% confidence interval, 1.20-6.49; P=0.017). The median occurrence time of primary end point was 9.9 (interquartile range, 5.0, 21.1) months in ISR group, earlier than that in non-ISR group (26.6 [13.1, 52.9] months; P=0.01). CONCLUSIONS: In-stent restenosis after stenting of intracranial atherosclerosis is significantly associated with an increased risk and an earlier occurrence of recurrent ischemic events in the territory of the stented intracranial artery.

Effectiveness of group acceptance and commitment therapy in treating depression for acute stroke patients.

OBJECTIVES: To date, the effectiveness of acceptance and commitment therapy (ACT) for acute stroke patients has not been well recognized. The study aimed to discover the effectiveness of group-based ACT in treating depression for acute stroke patients. METHODS: We conducted a randomized controlled trial with 140 acute stroke patients with depression. The ACT intervention comprised seven sessions, of 45-60 min over 4 weeks. Data were collected pre- and post-intervention and at 3-month follow-up, assessing depression, health-related quality of life (HRQoL), psychological flexibility, cognitive fusion, sleep quality, and confidence. RESULTS: Overall, 99.3% of the included patients were assessed as having mild depression. The ACT intervention significantly reduced depression in acute stroke patients in comparison with the control group post-intervention and at 3 months (partial η 2 = . 306 $\eta^{2}=.306$ ). Additionally ACT significantly improved HRQoL-mental component summary, sleep quality, psychological flexibility, cognitive fusion, and confidence compared with control group. CONCLUSIONS: ACT is effective in treating acute stroke patients with depression, and the efficacy was maintained at 3-month follow-up.

Behavioral and morphological evidence for the involvement of glial cells in the antinociceptive effect of najanalgesin in a rat neuropathic pain model.

Neuropathic pain is a devastating neurological disease that seriously affects patients' quality of life. Despite a high level of incidence, the underlying mechanisms of neuropathic pain are still poorly understood. However, recent evidence supports the prominent role of spinal glial cells in neuropathic pain states. In our laboratory, we observed that najanalgesin, a novel peptide isolated from the venom of Naja naja atra, exerts significant analgesic effects on acute pain in mice and neuropathic pain in rats. The objective of the present study was to determine whether spinal glia are associated with the antinociceptive effect of najanalgesin in an L5 spinal nerve ligation (SNL) rodent model of neuropathic pain. Mechanical allodynia developed after surgery, and hypersensitivity was significantly attenuated by the intrathecal administration of najanalgesin. The inhibitory effect of najanalgesin was significantly (p<0.05) enhanced after pretreatment with fluorocitrate (a glial cell antagonist). In addition, the astrocyte activation was attenuated following najanalgesin treatment in the dorsal horn of neuropathic rats, as assessed by immunohistology and Western blotting. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) content of cerebral spinal fluid and cell culture supernatants changed significantly after najanalgesin administration. The results suggest that najanalgesin may exert its anti-allodynic effect by altering astrocyte cell function.