Endovascular treatment versus standard medical treatment in patients with established large infarct: a cohort study.

BACKGROUND: Previous trials confirmed the benefit of endovascular treatment (EVT) in acute large core stroke, but the effect of EVT on outcomes in these patients based on non-contrast computed tomography (NCCT) in real-world clinical practice was unclear. The aim of this study was to explore the effect of EVT versus standard medical treatment (SMT) in patients with large ischemic core stroke defined as Alberta Stroke Program Early CT Score (ASPECTS)≤5 based on NCCT alone. MATERIALS AND METHODS: Patients with acute large core stroke at 38 Chinese centers between November 2021 and February 2023 were reviewed from prospectively maintained databases. The primary outcome was favorable functional outcome (modified Rankin Scale score [mRS], 0-3) at 90 days. Safety outcomes included 48-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. RESULTS: Of 745 eligible patients recruited at 38 stroke centers between November 2021 and February 2023, 490 were treated with EVT and 255 with SMT alone. One hundred and eighty-one (36.9%) in the EVT group achieved favorable functional independence versus 48 (18.8%) treated with SMT only (adjusted risk ratio [RR], 1.86; 95% CI, 1.43 to 2.42, P<0.001; adjusted risk difference [RD], 13.77; 95% CI, 7.40 to 20.15, P<0.001). The proportion of sICH was significantly higher in patients undergoing EVT (13.3% vs. 2.4%; adjusted RR, 5.17; 95% CI, 2.17 to 12.32, P<0.001; adjusted RD, 10.10; 95% CI, 6.12 to 14.09, P<0.001). No significant difference of mortality between the groups was observed (41.8% vs. 49.0%; adjusted RR, 0.91; 95% CI, 0.77 to 1.07, P=0.24; adjusted RD, -5.91; 95% CI, -12.91 to 1.09, P=0.1). CONCLUSION: Among patients with acute large core stroke based on NCCT in real world, EVT is associated with better functional outcomes at 90 days despite of higher risk of sICH. Rates of procedure-related complications were high in the EVT group.

Endovascular Therapy and Outcomes Among Patients With Very Large Ischemic Core Stroke.

Importance: The association of endovascular therapy (EVT) with outcomes is unclear for patients with very low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) within 24 hours of stroke onset. Objective: To explore the association of EVT with functional and safety outcomes among patients with ASPECTS of 0 to 2 scored with noncontrast computed tomography. Design, Setting, and Participants: This cohort study used data from an ongoing, prospective, observational, nationwide registry including all patients treated at 38 stroke centers in China with an occlusion in the internal carotid artery or M1 or M2 segment of the middle cerebral artery within 24 hours of witnessed symptom onset. Patients with ASPECTS of 0 to 2 between November 1, 2021, and February 8, 2023, were included in analysis. Data were analyzed October to November 2023. Exposures: EVT vs standard medical treatment (SMT). Main Outcomes and Measures: The primary outcome was favorable functional outcome, defined as modified Rankin Scale score (mRS) of 0 to 3, at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 48 hours and mortality at 90 days. Results: A total of 245 patients (median [IQR] age, 71 [63-78] years; 118 [48%] women) with ASPECTS of 0 to 2 were included, of whom 111 patients (45.1%) received SMT and 135 patients (54.9%) received EVT. The EVT group had significantly greater odds of favorable functional outcome at 90 days than the SMT group (30 patients [22.2%] vs 11 patients [9.9%]; P = .01; adjusted odds ratio [aOR], 3.07 [95% CI, 1.29-7.31]; P = .01). Patients in the EVT group, compared with the SMT group, had significantly greater odds of any ICH (56 patients [41.5%] vs 16 patients [11.4%]; P < .001; aOR, 4.27 [95% CI, 2.19-8.35]; P < .001) and sICH (24 patients [17.8%] vs 1 patient [0.9%]; P < .001; aOR, 23.07 [95% CI, 2.99-177.79]; P = .003) within 48 hours. There were no differences between groups for 90-day mortality (80 patients [59.3%] vs 59 patients [53.2%]; P = .34; aOR, 1.38 [95% CI, 0.77-2.47]; P = .28). The results remained robust in the propensity score-matched analysis. Conclusions and Relevance: In this cohort study of patients with very low ASPECTS based on NCCT within 24 hours of stroke onset, those treated with EVT had higher odds of a favorable functional outcome compared with those who received SMT. Randomized clinical trials are needed to assess these findings.

Combined effect of ASPECTS and age on outcome of patients with large core infarction treated with mechanical thrombectomy.

BACKGROUND: Despite the remarkable effectiveness of endovascular treatment (EVT), recent randomized controlled trials indicate that up to half of patients with large core infarction have a very poor outcome (modified Rankin Scale score 5-6 at 90 days). This study investigates the combined effect of Alberta Stroke Program Early CT Score (ASPECTS) and age on very poor outcome in patients with large core infarction treated with EVT. METHODS: This subanalysis of the MAGIC registry, which is a prospective, multicenter cohort study of early treatment in acute stroke, focused on patients with ASPECTS ≤5 presenting within 24 hours of stroke onset and receiving CT followed by EVT from November 1, 2021 to February 8, 2023. Multivariable logistic regression was used to investigate the independent and joint association of ASPECTS and age with very poor outcome. RESULTS: Among the 490 patients (57.3% men; median (IQR) age 69 (59-78) years), very poor outcome occurred more frequently in those with lower ASPECTS (65.2% in ASPECTS 0-2 vs 43.4% in ASPECTS 3-5; P<0.001). The predictive value of successful recanalization for very poor outcome was significant in patients with ASPECTS 3-5 (P=0.010), but it diminished in those with ASPECTS 0-2 (P=0.547). Compared with patients with ASPECTS 3-5 and age ≤69 years, the risk of a very poor outcome increased incrementally in those with lower ASPECTS, advanced age, or both (P<0.05). Graphical plot analysis showed a significantly lower probability of very poor outcome in younger patients (≤69 years) compared with older patients (>69 years) across all ASPECTS points. CONCLUSION: These findings suggest prioritizing young patients as candidates for EVT in those with ASPECTS 0-2.

Pomalidomide improves the effectiveness of CAR-T treatment in the relapsed and refractory multiple myeloma or B-cell leukemia/lymphoma with extramedullary disease.

Relapsed and refractory multiple myeloma (RRMM) and B-cell leukemia/lymphoma with extramedullary disease (EMD) have poor prognosis and high mortality, lack of effective therapeutic approaches. We reported for the first time that 6 patients with malignant hematological diseases with EMD received chimeric antigen receptor (CAR)-T treatment combined with pomalidomide, and CAR-T cells were treated with pomalidomide in vitro to determine its killing activity and cytokine secretion. Three patients with RRMM were given B cell maturation antigen (BCMA)-CAR-T therapy. All 3 patients with B-cell leukemia/lymphoma received CD19/22-CAR-T sequential infusion. There were no treatment-related deaths. The maximum overall response rate (ORR) was 100%. Median follow-up was 211.5 days (75-407 days). Three patients (50%) experienced cytokine release syndrome, all of which were grade 1, and no neurotoxicity was observed. In vitro experiments showed that the killing activity did not differ significantly between BCMA-CAR-T cells with and without pomalidomide (10, 25, or 50 µg/mL) in 8226/U266 cell cocultures (P > .05). Tumor necrosis factor (TNF)-α and interferon (IFN)-γ secretion was significantly higher from 8226 and Raji cells cocultured with BCMA-CAR-T and cluster of differentiation (CD)19-CAR-T cells (P < .05). Based on the cocultures, adding pomalidomide significantly promoted IFN-γ and TNF-α secretion (P < .05). Based on the above clinical and in vitro studies demonstrating the co-administration of pomalidomide with CAR-T cell treatment demonstrated favorable tolerability and therapeutic effectiveness in RRMM or B-cell leukemia/lymphoma.

Differential contribution of canonical and noncanonical NLGN3 pathways to early social development and memory performance.

Neuroligin (NLGN) 3 is a postsynaptic cell adhesion protein organizing synapse formation through two different types of transsynaptic interactions, canonical interaction with neurexins (NRXNs) and a recently identified noncanonical interaction with protein tyrosine phosphatase (PTP) δ. Although, NLGN3 gene is known as a risk gene for neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID), the pathogenic contribution of the canonical NLGN3-NRXN and noncanonical NLGN3-PTPδ pathways to these disorders remains elusive. In this study, we utilized Nlgn3 mutant mice selectively lacking the interaction with either NRXNs or PTPδ and investigated their social and memory performance. Neither Nlgn3 mutants showed any social cognitive deficiency in the social novelty recognition test. However, the Nlgn3 mutant mice lacking the PTPδ pathway exhibited significant decline in the social conditioned place preference (sCPP) at the juvenile stage, suggesting the involvement of the NLGN3-PTPδ pathway in the regulation of social motivation and reward. In terms of learning and memory, disrupting the canonical NRXN pathway attenuated contextual fear conditioning while disrupting the noncanonical NLGN3-PTPδ pathway enhanced it. Furthermore, disruption of the NLGN3-PTPδ pathway negatively affected the remote spatial reference memory in the Barnes maze test. These findings highlight the differential contributions of the canonical NLGN3-NRXN and noncanonical NLGN3-PTPδ synaptogenic pathways to the regulation of higher order brain functions associated with ASD and ID.

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

The impact of stress hyperglycemia ratio on short-term and long-term outcomes for acute basilar artery occlusion underwent endovascular treatment.

BACKGROUND: Stress hyperglycemia ratio (SHR) reflects a true acute hyperglycemic state during acute basilar artery occlusion (ABAO). We aimed to investigate the association between SHR and short-term and long-term outcomes in patients with ABAO receiving endovascular treatment (EVT). METHODS: We selected patients treated with EVT from the BASILAR study, a nationwide prospective registry. A total 250 patients with documented glucose and glycated hemoglobin (HbA1C) values at admission were included. SHR was calculated as the ratio of glucose/HbA1C. All 250 patients completed 90 days of follow-up and 234 patients (93.6%) completed 1 year of follow-up. The primary outcome was the favorable outcome defined as modified Rankin Scale (mRS) score ≤ 3 at 90 days. Safety outcomes included mortality at 90 days and 1 year, and intracranial hemorrhage. RESULTS: Among the 250 patients included, patients with higher tertiles of SHR were associated with decreased odds of a favorable functional outcome at 90 days (adjusted OR, 0.26; 95% CI, 0.12-0.56; P = 0.001 and adjusted OR, 0.37; 95% CI, 0.18-0.80; P = 0.01; respectively) and 1 year (adjusted OR, 0.34; 95% CI, 0.16-0.73; P = 0.006 and adjusted OR, 0.38; 95% CI, 0.18-0.82; P = 0.01; respectively) after adjusting for confounding covariates. The mortality was comparable across tertiles of SHR groups at 90 days and 1 year. CONCLUSIONS: Our study showed that SHR was associated with a decreased probability of favorable functional outcome both at 90 days and 1 year after EVT in patients with ABAO. The relationship was more pronounced in non-diabetes patients. TRIAL REGISTRATION: Clinical Trial Registry Identifier: ChiCTR1800014759 (November 12, 2013).

Peptide-based probe for colorimetric and fluorescent detection of Cu2+ and S2- in environmental and biological systems.

Pollution caused by Copper and hydrogen sulfide pollution has severe adverse effects on the environment and organisms. Real-time, fast and accurate monitoring of Cu2+ and S2- faces serious challenges. In this study, we designed a novel biosensor and synthesized it by mimicking the structure of the main Cu(II)-binding site on bovine serum albumin. As a peptide-based sensor, FGGH (FITC-Gly-Gly-His-NH2) can perform the sequential detection of Cu2+ and S2- by fluorescence and colorimetry. The high water solubility and selectivity make it suitable for monitoring Cu2+ and S2- in environmental water samples with high sensitivity; its limit of detection (LOD) is as low as 1.42 nM for Cu2+ and 22.2 nM for S2-. The paper-based sensing platform of this probe was found to be a promising tool for the on-site visualization of real-time quantitative analysis of Cu2+ and S2- due to its rapid response and recyclable detection characteristics. Additionally, FGGH was successfully used to image Cu2+ and S2- in living cells and zebrafish models with adequate fluorescence stability and low cytotoxicity, providing the first visual evidence of the effect of the interactions between Cu2+ and S2- on the redox homeostasis of organisms.

The Initial Efficacy of Comprehensive Treatment of External Treatment of Traditional Chinese Medicine on Acute Mastitis During Lactation and its Influence on Patients' Symptoms.

Objective: To evaluate the initial efficacy of comprehensive treatment of external treatment of traditional Chinese medicine in the therapy of acute mastitis during lactation and its influence on sufferers' symptoms. Methods: From January 2021 to January 2023, a retrospective analysis was performed on 100 sufferers with acute mastitis during lactation who were received in our hospital as the study objects. Divided them into a control group (n = 50) and an observation group (n = 50). Among them, the control one was received in 50% magnesium sulfate for moist heat compress, and the observation one was treated with comprehensive external therapy of traditional Chinese medicine. After different treatment measures were carried out in the 2 groups, the total effective ratio of clinical therapy, excellent and good rates of lactation, quality of life measurements, pain scores before and after treatment, and TCM symptom points at pre-therapy and post-therapy, negative emotion scores at pre-therapy and post-therapy related to patients were analyzed. Results: (1) In the data comparison of the total effective ratio of clinical therapy between the 2 groups of sufferers after therapy, the data in the observation one were greater than the control one, and the distinction was obvious, with P < .05. (2) In the data comparison of the excellent and good lactation rate between the 2 groups of sufferers at post-therapy, the data in observation one were greater than the control one, and the distinction was obvious, with P < .05. (3) In the data comparison of quality of life measurements between the 2 groups of sufferers at post-therapy, the data in the observation one were greater than the control one, and the distinction was obvious, with P < .05. (4) Before treatment, it had no obvious distinction in the pain scores between the 2 groups, with P > .05; in the data comparison of the pain points between the 2 groups after therapy, the data in observation one were less than the control one, and the distinction was obvious, with P < .05. (5) Before therapy, it had no obvious distinction in TCM symptom points between the 2 groups, with P > .05; in the data comparison of TCM symptom points between the 2 groups after therapy, the data in the observation one were less than the control one, and the distinction was obvious, with P < .05. (6) Before therapy, it had no obvious distinction in negative emotion points between the 2 groups, with P > .05; in the data comparison of negative emotion scores between the 2 groups of sufferers at post-therapy, the data in the observation one were less than those in the control one, and the distinction was obvious, with P < .05. Conclusion: The comprehensive therapy of TCM external treatment for acute mastitis during lactation has a significant therapeutic effect, which is conducive to improving the clinical symptoms of sufferers as soon as possible and at the same time, greatly improving the life quality of sufferers and improving their negative emotions, which can relieve the pain of sufferers and promote the recovery of the sufferers.

The theory of critical flicker fusion frequency and its application in cataracts.

Background: Due to media opacity, it is usually difficult to accurately evaluate the postoperative visual acuity in cataracts patients. As a small and portable tool, the critical flicker fusion frequency (CFF) device reflects the temporal resolution of visual function and has been widely used in clinical research. However, poor understanding of the technique and equipment limitations have restricted its clinical application in China. Main text: There was a decrease in the CFF value in various ophthalmic diseases, indicating that the CFF is sensitive to detect visual functional changes. A number of studies have shown that the CFF test can accurately distinguish patients with simple cataracts from those with cataracts combined with fundus disease, and, as a visual test, it can more accurately predict postoperative visual acuity without being affected by media opacity. This study comprehensive reviews the basic principles of CFF and its application in ophthalmology, especially in cataracts. Conclusions: As one of the tools for dynamic visual function detection, the CFF test could help doctors to assess the possible presence of fundus disease in cataracts patients, especially in eyes with dense cataracts, and more precisely provide a reasonable visual prognosis than other available visual tests.

Pharmacological action of Hedysarum polysaccharides: a review.

Hedysarum, a traditional Chinese herbal medicine and food with a long history of clinical application, is used to improve health conditions and treat various diseases. Hedysarum polysaccharides (HPS), flavonoids, saponins, and alkaloids, are the primary components of Hedysarum. HPS is the most important natural active ingredient of Hedysarum, which has many pharmacological effects. Currently, HPS exhibits significant promise in drug development for various ailments such as tumors, diabetes, cardiovascular diseases, Alzheimer's disease, and fibrosis. This review paper discusses the extraction, separation, and content determination techniques of HPS, along with the investigation of its chemical constituents. More importantly, we reviewed the anti-inflammatory pharmacological effects of HPS, such as inhibition of inflammatory factors and NF-κB signaling pathway; antitumor activity through apoptosis induction in tumor cells and blocking tumor cell proliferation and metastasis; antioxidant effects; regulation of various cytokines and immune cells; regulation of blood sugar levels, such as in type I and type II diabetes and in diabetic complications; improvement in symptoms of Alzheimer disease; anti-aging and anti-fibrosis properties; and improvement in cerebral ischemia-reperfusion injury. This review paper establishes the theoretical foundation for future studies on the structure, mechanism, and clinical use of HPS.

Intravenous tirofiban following successful reperfusion in intracranial large artery atherosclerotic stroke: A secondary analysis of a randomized clinical trial.

OBJECTIVE: This study aimed to investigate whether treatment with adjunct intravenous tirofiban is associated with improved outcomes following successful reperfusion in patients with intracranial atherosclerotic stroke. METHODS: Patients with intracranial large artery atherosclerotic (LAA) stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 from the Effect of Intravenous Tirofiban versus Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke (RESCUE BT) trial were included. The primary outcome was the difference in proportion of independent functional outcome (modified Rankin score of 0-2 at 90 days). Safety outcomes included the rates of symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: Among the 382 patients with intracranial LAA stroke and successful reperfusion, 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95 out of 175) with tirofiban and 44.0% (91 out of 207) with placebo (adjusted odds ratio [aOR], 1.58; 95% CI, 1.02-2.44; p = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of sICH (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59-3.34; p = 0.44) or 90-day mortality (21/175 [12.0%] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38-1.31; p = 0.27). INTERPRETATION: Among patients with acute intracranial LAA stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of sICH or mortality. Confirmatory randomized trials in these patients are desirable.

Construction and validation of a predictive risk model for nosocomial infections with MDRO in NICUs: a multicenter observational study.

Objectives: This study aimed to construct and validate a predictive risk model (PRM) for nosocomial infections with multi-drug resistant organism (MDRO) in neonatal intensive care units (NICUs), in order to provide a scientific and reliable prediction tool, and to provide reference for clinical prevention and control of MDRO infections in NICUs. Methods: This multicenter observational study was conducted at NICUs of two tertiary children's hospitals in Hangzhou, Zhejiang Province. Using cluster sampling, eligible neonates admitted to NICUs of research hospitals from January 2018 to December 2020 (modeling group) or from July 2021 to June 2022 (validation group) were included in this study. Univariate analysis and binary logistic regression analysis were used to construct the PRM. H-L tests, calibration curves, ROC curves and decision curve analysis were used to validate the PRM. Results: Four hundred and thirty-five and one hundred fourteen neonates were enrolled in the modeling group and validation group, including 89 and 17 neonates infected with MDRO, respectively. Four independent risk factors were obtained and the PRM was constructed, namely: P = 1/ (1+ e-X), X = -4.126 + 1.089× (low birth weight) +1.435× (maternal age ≥ 35 years) +1.498× (use of antibiotics >7 days) + 0.790× (MDRO colonization). A nomogram was drawn to visualize the PRM. Through internal and external validation, the PRM had good fitting degree, calibration, discrimination and certain clinical validity. The prediction accuracy of the PRM was 77.19%. Conclusion: Prevention and control strategies for each independent risk factor can be developed in NICUs. Moreover, clinical staff can use the PRM to early identification of neonates at high risk, and do targeted prevention to reduce MDRO infections in NICUs.

Association Between Admission Hyperglycemia and Outcomes After Endovascular Treatment in Acute Basilar Artery Occlusion.

INTRODUCTION: Admission hyperglycemia and high admission blood glucose levels have been associated with poor outcomes in acute ischemic stroke. However, the relationship between admission hyperglycemia and outcomes after endovascular treatment (EVT) in acute basilar artery occlusion (ABAO) still remain unclear. This study aimed to investigate the association between admission hyperglycemia and clinical outcomes in ABAO following EVT. METHODS: Patients from the BASILAR registry with admission blood glucose levels treated with EVT were included. We defined admission hyperglycemia as blood glucose levels ≥ 7.8 mmol/L. The primary outcome was favorable outcome [defined as a modified Rankin Scale score (mRS) of 0-3] at 90 days, Secondary outcomes included other functional outcomes (mRS 0-2, mRS 0-1) at 90 days, symptomatic intracerebral hemorrhage (sICH) within 48 h, and mortality at 90 days. RESULTS: Of 545 eligible patients included, the median age was 65 (IQR, 56-73) years, and median blood glucose level was 7.36 (IQR, 6.10-9.66) mmol/L. Multivariable logistic regression analysis showed that admission hyperglycemia was associated with decreased favorable outcome (mRS 0-3) (adjusted odds ratio = 0.52; 95% CI 0.35-0.79; P = 0.001), and increased mortality (adjusted odds ratio = 2.67; 95% CI 1.82-3.91; P < 0.001). Restricted cubic spline regression analysis showed that the blood glucose level had a non-linearity association with favorable outcome and mortality, and that there was no association between admission hyperglycemia and sICH. CONCLUSIONS: Our study suggest that admission hyperglycemia is associated with an increased risk of poor functional outcomes and mortality in patients with ABAO treated with EVT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR180001475.

Advances of ionic liquid-based nanohybrids for biomedical applications.

Ionic liquids (ILs) are composed of asymmetric cationic and anionic moieties and are used as green solvents. Their non-toxic nature, favorable biocompatibility and adjustable structure facilitate wide biomedical applications. ILs promote the generation of various nanohybrids that exhibit multiple functions and novel/improved properties with respect to their precursors. Generally, nanostructures have a large specific surface area and abundant functional groups which enable loading and incorporation of ILs through physical interactions or chemical bonding. According to their main skeleton structures, IL-based nanohybrids may be divided into five categories, i.e., poly(ionic liquid)s (PILs), IL-inorganic nanohybrids, IL-metal organic framework nanohybrids (IL-MOF nanohybrids), ILs/carbon materials and ionic materials. These IL-based nanohybrids exhibit various specific features, including thermal responsive behavior, metal chelating, photothermal conversion and antibacterial capabilities. Taking advantage of these characteristics, IL-based nanohybrids may overcome the shortcomings of conventional medicines/drugs and exhibit promising prospects in biomedicine to facilitate controlled drug release, bactericidal treatment and thermotherapy. The present review presents the state-of-the-art progress made in the studies of IL-based nanohybrids in terms of their classifications, structure characteristics, versatile functionalities and biomedical and pharmaceutical applications. The challenges and future perspectives in the developments and applications of IL-based nanohybrids in biomedicine are discussed.

Construction and Evaluation of the Immunogenicity and Protective Efficacy of Recombinant Replication-Deficient Human Adenovirus-5 Expressing Genotype VII Newcastle Disease Virus F Protein and Infectious Bursal Disease Virus VP2 Protein.

Newcastle disease (ND) and infectious bursal disease (IBD) are two key infectious diseases that significantly threaten the health of the poultry industry. Although existing vaccinations can effectively prevent and treat these two diseases through multiple immunizations, frequent immunization stresses significantly impact chicken growth. In this study, three recombinant adenoviruses, rAd5-F expressing the NDV (genotype VII) F protein, rAd5-VP2 expressing the IBDV VP2 protein, and rAd5-VP2-F2A-F co-expressing F and VP2 proteins, were constructed using the AdEasy system. The F and VP2 genes of the recombinant adenoviruses could be transcribed and expressed normally in HEK293A cells as verified by RT-PCR and Western blot. The three recombinant viruses were shown to have similar growth kinetics as rAd5-EGFP. Compared with the PBS and rAd5-EGFP groups, SPF chickens immunized with recombinant adenoviruses produced higher antibody levels, more significant lymphocyte proliferation, and significantly higher CD4+/CD3+ and CD8+/CD3+ cells in peripheral blood. The survival rate of SPF chickens immunized with rAd5-F and rAd5-VP2-F2A-F after the challenge with DHN3 was 100%, and 86% of SPF chickens showed no viral shedding at 7 dpc. The survival rate of SPF chickens immunized with rAd5-VP2 and rAd5-VP2-F2A-F after the challenge with BC6/85 was 86%. rAd5-VP2 and rAd5-VP2-F2A-F significantly inhibited bursal atrophy and pathological changes compared to the rAd5-EGFP and PBS groups. This study provides evidence that these recombinant adenoviruses have the potential to be developed into safe and effective vaccine candidates for the prevention and control of ND and IBD.

Deficiency of neuropeptide Y attenuates neointima formation after vascular injury in mice.

BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) limits therapeutic revascularization. Neuropeptide Y (NPY), co-stored and co-released with the sympathetic nervous system, is involved in this process, but its exact role and underlying mechanisms remain to be fully understood. This study aimed to investigate the role of NPY in neointima formation after vascular injury. METHODS: Using the left carotid arteries of wild-type (WT, NPY-intact) and NPY-deficient (NPY-/-) mice, ferric chloride-mediated carotid artery injury induced neointima formation. Three weeks after injury, the left injured carotid artery and contralateral uninjured carotid artery were collected for histological analysis and immunohistochemical staining. RT-qPCR was used to detect the mRNA expression of several key inflammatory markers and cell adhesion molecules in vascular samples. Raw264.7 cells were treated with NPY, lipopolysaccharide (LPS), and lipopolysaccharide-free, respectively, and RT-qPCR was used to detect the expression of these inflammatory mediators. RESULTS: Compared with WT mice, NPY-/- mice had significantly reduced neointimal formation three weeks after injury. Mechanistically, immunohistochemical analysis showed there were fewer macrophages and more vascular smooth muscle cells in the neointima of NPY-/- mice. Moreover, the mRNA expression of key inflammatory markers such as interleukin-6 (IL-6), transforming growth factor-ß1 (TGF-ß1), and intercellular adhesion molecule-1 (ICAM-1) was significantly lower in the injured carotid arteries of NPY-/- mice, compared to that in the injured carotid arteries of WT mice. In RAW264.7 macrophages, NPY significantly promoted TGF-ß1 mRNA expression under unactivated but not LPS-stimulated condition. CONCLUSIONS: Deletion of NPY attenuated neointima formation after artery injury, at least partly, through reducing the local inflammatory response, suggesting that NPY pathway may provide new insights into the mechanism of restenosis.

Effect of Imaging Selection Paradigms on Endovascular Thrombectomy Outcomes in Patients With Acute Ischemic Stroke.

BACKGROUND: The effect of imaging selection paradigms on endovascular thrombectomy outcomes in patients with acute ischemic stroke with large vessel occlusion remains uncertain. The study aimed to assess the effect of basic imaging (noncontrast computed tomography with or without computed tomographic angiography) versus advanced imaging (magnetic resonance imaging or computed tomography perfusion) on clinical outcomes following thrombectomy in patients with stroke with large vessel occlusion in the early and extended windows using a pooled analysis of patient-level data from 2 pivotal randomized clinical trials done in China. METHODS: This post hoc analysis used data from 1182 patients included in 2 multicenter, randomized controlled trials in China that evaluated adjunct therapies to endovascular treatment for acute ischemic stroke (Direct Endovascular Treatment for Large Artery Anterior Circulation Stroke performed from May 20, 2018, through May 2, 2020, and Intravenous Tirofiban Before Endovascular Treatment in Stroke from October 10, 2018, through October 31, 2021). Patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery (M1/M2 segments) were categorized according to baseline imaging modality (basic versus advanced) as well as treatment time window (early, 0-6 hours versus extended, 6-24 hours from last known well to puncture). The primary outcome was the proportion of patients with functional independence (modified Rankin Scale score of 0-2) at 90 days. Multivariable Poisson regression analysis was performed to determine the association between imaging selection modality and outcomes after endovascular treatment at each time windows. RESULTS: A total of 1182 patients were included in this cohort analysis, with 648 in the early (471 with basic imaging versus 177 advanced imaging) and 534 in the extended (222 basic imaging versus 312 advanced imaging) time window. There were no differences in 90-day functional independence between the advanced and basic imaging groups in either time windows (early window: adjusted relative risk, 0.99 [95% CI, 0.84-1.16]; P=0.91; extended window: adjusted relative risk, 1.00 [95% CI, 0.84-1.20]; P=0.97). CONCLUSIONS: In this post hoc analysis of 2 randomized clinical trial pooled data involving patients with large vessel occlusion stroke, an association between imaging selection modality and clinical or safety outcomes for patients undergoing thrombectomy in either the early or extended windows was not detected. Our study adds to the growing body of literature on simpler imaging paradigms to assess thrombectomy eligibility across both the early and extended time windows. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Association of Procedure Time With Clinical and Procedural Outcome in Patients With Basilar Occlusion Undergoing Embolectomy.

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated the association between the procedure time (PT) and outcomes for patients with proximal large vessel occlusion; however, whether the relationship remains for patients with acute basilar artery occlusion (ABAO) was not clear. We aimed to characterize the association between PT and other procedure-related variables on clinical outcomes among patients with ABAO who underwent endovascular treatment (EVT). METHODS: Patients with ABAO who underwent EVT with a documented PT in the EVT for Acute Basilar Artery Occlusion (BASILAR) study from January 2014 to May 2019 among 47 comprehensive centers in China were included. Multivariable analysis was performed to reveal the association between PT and 90-day modified Rankin Scale score, mortality, complications, and all-cause death at 1 year. RESULTS: Of the 829 patients from the BASILAR registry, 633 eligible patients were included. Longer PT were associated with a lower rate of favorable outcome (by 30 minutes, adjusted OR 0.82 [95% CI 0.72-0.93], p = 0.01). In addition, a PT ≤ 75 minutes was associated with a favorable outcome (adjusted OR 2.03 [95% CI 1.26-3.28]). The risk of complications and mortality increased by 0.5% and 1.5% with every 10 minutes increase in PT, respectively (R2 = 0.64 and R2 = 0.68, p < 0.01). The cumulative rates of favorable outcomes and successful recanalization plateaued after 120 minutes (2 attempts). Restricted cubic spline regression analysis for the probability of favorable outcomes had an L-shape association (p nonlinearity = 0.01) with PT with significant benefit loss before 120 minutes and then appeared relatively flat. DISCUSSION: For patients with ABAO, procedures that exceeded 75 minutes were associated with an increased risk of mortality and lower odds of a favorable outcome. A careful assessment of futility and the risks of continuing the procedure should be made after 120 minutes.

Association between stress hyperglycemia and outcomes in patients with acute ischemic stroke due to large vessel occlusion.

AIMS: This study aimed to evaluate the association between stress hyperglycemia ratio (SHR) and clinical outcomes at 90 days in acute ischemic stroke due to large vessel occlusion receiving endovascular treatment. METHODS: The RESCUE BT trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial, consisting of 948 stroke patients from 55 centers in China. A total of 542 patients with glucose and glycated hemoglobin (HbA1C) values at admission were included in this analysis. SHR, measured by glucose/HbA1C, was evaluated as both a tri-categorical variable (≤1.07 vs. 1.08-1.29 vs. ≥1.30) and a continuous variable. The primary outcome was a favorable functional outcome (modified Rankin Scale [mRS] score ≤2) at 90 days. The secondary outcome included excellent functional outcome (mRS score ≤1) and safety outcomes, such as 90-day mortality and intracranial hemorrhage. The study was registered with Chictr.org.cn (ChiCTR-INR-17014167). RESULTS: Compared with patients in the lowest tertile of SHR, the highest tertile group had significantly lower odds of achieving favorable functional outcome of mRS score of 0-2 (adjusted odds ratio, 0.44; 95% confidence interval, 0.28-0.69; p < 0.001) and excellent clinical outcome of mRS score of 0-1 (adjusted odds ratio, 0.48; 95% confidence interval, 0.29-0.79; p = 0.004) at 90 days after adjusting for potential covariates. Similar results were observed after further adjustment for preexisting diabetes and Alberta Stroke Program Early Computed Tomography Score (ASPECTS). CONCLUSION: Stress hyperglycemia ratio, as measured by the glucose/HbA1C, was associated with a decreased odds of achieving a favorable functional outcome in patients with acute large vessel occlusion stroke at 90 days.