Porous metallic cubic boron nitride (CBN) composites with 50 vol.% porosity were prepared by using water soluble spherical carbamide particles as pore-forming agents. Graphene nanoparticles were ...employed in porous metallic CBN composites via a conventional vacuum sintering technique to strengthen the mechanical property of as-sintered samples. In order to investigate the influence of graphene nanoparticles on the strengthening mechanism and microstructure of porous metallic composites, various graphene concentrations (0, 0.005, 0.01, 0.05, 0.05, and 0.1 wt.%) were incorporated. Characterization of morphology characteristics, such as macropores, micropores, and interfaces between CBN abrasive grains and metallic matrix, were carried out. Results show that addition of graphene nanoparticles up to 0.01 wt.% improves the flexural strength of the as-sintered composites. Micropores within as-sintered samples rapidly increase with graphene nanoparticles concentrations and severely affect the mechanical strength of metallic composites. And then samples containing a higher graphene nanoparticles concentration have larger cracks around CBN abrasive grains. In addition, the grain fracture modes ranging from the trans-granular fracture to inter-granular fracture are observed as graphene nanoparticle concentrations increase. The mass fraction of graphene concentrations is optimized as 0.01 wt.% in terms of the friction coefficient, wear morphology, and microstructure.
The effects and risks of endovascular thrombectomy 6 to 24 hours after stroke onset due to basilar-artery occlusion have not been extensively studied.
In a trial conducted over a 5-year period in ...China, we randomly assigned, in a 1:1 ratio, patients with basilar-artery stroke who presented between 6 to 24 hours after symptom onset to receive either medical therapy plus thrombectomy or medical therapy only (control). The original primary outcome, a score of 0 to 4 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 4 moderately severe disability, and 6 death) at 90 days, was changed to a good functional status (a modified Rankin scale score of 0 to 3, with a score of 3 indicating moderate disability). Primary safety outcomes were symptomatic intracranial hemorrhage at 24 hours and 90-day mortality.
A total of 217 patients (110 in the thrombectomy group and 107 in the control group) were included in the analysis; randomization occurred at a median of 663 minutes after symptom onset. Enrollment was halted at a prespecified interim analysis because of the superiority of thrombectomy. Thrombolysis was used in 14% of the patients in the thrombectomy group and in 21% of those in the control group. A modified Rankin scale score of 0 to 3 (primary outcome) occurred in 51 patients (46%) in the thrombectomy group and in 26 (24%) in the control group (adjusted rate ratio, 1.81; 95% confidence interval CI, 1.26 to 2.60; P<0.001). The results for the original primary outcome of a modified Rankin scale score of 0 to 4 were 55% and 43%, respectively (adjusted rate ratio, 1.21; 95% CI, 0.95 to 1.54). Symptomatic intracranial hemorrhage occurred in 6 of 102 patients (6%) in the thrombectomy group and in 1 of 88 (1%) in the control group (risk ratio, 5.18; 95% CI, 0.64 to 42.18). Mortality at 90 days was 31% in the thrombectomy group and 42% in the control group (adjusted risk ratio, 0.75; 95% CI, 0.54 to 1.04). Procedural complications occurred in 11% of the patients who underwent thrombectomy.
Among patients with stroke due to basilar-artery occlusion who presented 6 to 24 hours after symptom onset, thrombectomy led to a higher percentage with good functional status at 90 days than medical therapy but was associated with procedural complications and more cerebral hemorrhages. (Funded by the Chinese National Ministry of Science and Technology; BAOCHE ClinicalTrials.gov number, NCT02737189.).
Carotid artery stenting (CAS) is an alternative treatment to carotid endarterectomy for carotid artery stenosis. Acute stent thrombosis (ACST) is an extremely rare complication but can have ...devastating consequences. Although many cases have been reported, the best treatment is still uncertain. In this study, we report the treatment of ACST caused by diarrhea in an intermediate clopidogrel metabolizer. We also review the literature and discuss appropriate treatment strategies for this rare event.
Symptomatic intracranial hemorrhage (SICH) pose a major safety concern for endovascular treatment of acute ischemic stroke. This study aimed to evaluate the risk and related factors of SICH after ...endovascular treatment in a real-world practice.
Patients with stroke treated with stent-like retrievers for recanalizing a blocked artery in anterior circulation were enrolled from 21 stroke centers in China. Intracranial hemorrhage was classified as symptomatic and asymptomatic ones according to Heidelberg Bleeding Classification. Logistic regression was used to identify predictors for SICH.
Of the 632 enrolled patients, 101 (16.0%) were diagnosed with SICH within 72 hours after endovascular treatment. Ninety-day mortality was higher in patients with SICH than in patients without SICH (65.3% versus 18.8%;
<0.001). On multivariate analysis, baseline neutrophil ratio >0.83 (odds ratio OR, 2.07; 95% confidence interval CI, 1.24-3.46), pretreatment Alberta Stroke Program Early Computed Tomography Score of <6 (OR, 2.27; 95% CI, 1.24-4.14), stroke of cardioembolism type (OR, 1.91; 95% CI, 1.13-3.25), poor collateral circulation (OR, 1.97; 95% CI, 1.16-3.36), delay from symptoms onset to groin puncture >270 minutes (OR, 1.70; 95% CI, 1.03-2.80), >3 passes with retriever (OR, 2.55; 95% CI, 1.40-4.65) were associated with SICH after endovascular treatment.
Incidence of SICH after thrombectomy is higher in Asian patients with acute ischemic stroke. Cardioembolic stroke, poor collateral circulation, delayed endovascular treatment, multiple passes with stent retriever device, lower pretreatment Alberta Stroke Program Early Computed Tomography Score, higher baseline neutrophil ratio may increase the risk of SICH.
Cancer stem cells (CSCs) are a small population of cells in tumor tissues that can drive tumor initiation and promote tumor progression. A small number of previous studies indirectly mentioned the ...role of F-box and WD repeat domain-containing 7 (FBXW7) as a tumor suppressor in Triple-negative breast cancer (TNBC). However, few studies have focused on the function of FBXW7 in cancer stemness in TNBC and the related mechanism.
We detected FBXW7 by immunohistochemistry (IHC) in 80 TNBC patients. FBXW7 knockdown and overexpression in MD-MBA-231 and HCC1937 cell models were constructed. The effect of FBXW7 on malignant phenotype and stemness was assessed by colony assays, flow cytometry, transwell assays, western blot, and sphere formation assays. Immunoprecipitation-Mass Spectrometry (IP-MS) and ubiquitination experiments were used to find and verify potential downstream substrate proteins of FBXW7. Animal experiments were constructed to examine the effect of FBXW7 on tumorigenic potential and cancer stemness of TNBC cells in vivo.
The results showed that FBXW7 was expressed at low levels in TNBC tissues and positively correlated with prognosis of TNBC patients. In vitro, FBXW7 significantly inhibited colony formation, cell cycle progression, cell migration, EMT process, cancer stemness and promotes apoptosis. Further experiments confirmed that chromodomain-helicase-DNA-binding protein 4 (CHD4) is a novel downstream target of FBXW7 and is downregulated by FBXW7 via proteasomal degradation. Moreover, CHD4 could promote the nuclear translocation of β-catenin and reverse the inhibitory effect of FBXW7 on β-catenin, and ultimately activate the Wnt/β-catenin pathway. Rescue experiments confirmed that the FBXW7-CHD4-Wnt/β-catenin axis was involved in regulating the maintenance of CSC in TNBC cells. In animal experiments, FBXW7 reduced CSC marker expression and suppressed TNBC cell tumorigenesis in vivo.
Taken together, these results highlight that FBXW7 degrades CHD4 protein through ubiquitination, thereby blocking the activation of the Wnt/β-catenin pathway to inhibit the stemness of TNBC cells. Thus, targeting FBXW7 may be a promising strategy for therapeutic intervention against TNBC.
The relationship between heart rate and the prognosis of patients with large vessel occlusion strokes treated with mechanical thrombectomy (MT) is not well established. This study aimed to evaluate ...the association of mean heart rate and heart rate variability (HRV) with the clinical outcomes after MT therapy.
Acute ischemic stroke patients undergoing MT therapy were prospectively recruited from March 2020 to November 2022. Their heart rate was collected every hour for the initial 72 h after MT procedure, and the variability of heart rate was measured by standard deviation (SD) and coefficient of variation (CV). All-cause mortality and worsening of functional outcome (change in modified Rankin Scale (mRS) score) at 3-month were captured. Binary logistic regression was used to evaluate the association between heart rate indicators and all-cause mortality. Ordinal logistic regression was used to evaluate the association between heart rate indicators and worsening of functional outcome.
Among 191 MT-treated patients, 51(26.7%) patients died at 3-month after stroke. Increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were all associated with the increased risk of mortality (adjusted hazard ratio aHR with 95% CI: 1.29 1.09-1.51, 1.19 1.07-1.32, 1.14 1.03-1.27; respectively). Patients in the highest tertile of heart rate SD had an increased risk of mortality (4.62, 1.70-12.52). After using mRS as a continuous variable, we found increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were associated with the worsening of functional outcome (adjusted odds ratio aOR with 95% CI: 1.35 1.11-1.64, 1.27 1.05-1.53, 1.19 1.02-1.40; respectively). A linear relationship was observed between mean heart rate or heart rate SD and mortality; while all of the heart rate measures in this study showed a linear relationship with the worsening of functional outcome.
Higher mean heart rate and HRV were associated with the increased risk of 3-month all-cause mortality and worse functional outcome after MT therapy for AIS patients.
Aims
This study aimed to observe the efficacy and safety of anlotinib in the treatment of small cell lung cancer (SCLC) in the real world, as first-line maintenance therapy, second-line, and above.
...Methods
Clinical data of 109 patients with SCLC treated with anlotinib and hospitalized at The First Affiliated Hospital of Zhengzhou University from June 2018 to June 2020 were retrospectively analyzed. Analysis of short-term efficacy and survival was performed, with
p
<0.05 being considered statistically significant.
Results
The median progression-free survival (mPFS) of anlotinib monotherapy used as first-line maintenance treatment of SCLC was 6.3 months (11.7 months in the limited phase and 5.8 months in the extensive phase) and median overall survival (mOS) was 16.7 months (not reached in limited phase, 12.6 months in extensive phase). In second-line treatment, anlotinib with chemotherapy prolonged PFS and OS as compared to anlotinib monotherapy (
p
<0.05). In third-line and above treatment, there was no improvement in mPFS with the chemotherapy combination regimen compared to anlotinib monotherapy (3.6 months vs. 3.8 months,
p=0
.398), with a trend toward impaired mOS (8.5 months vs. not achieved,
p=0
.060). Univariate analyses and multivariate analyses revealed that Eastern Cooperative Oncology Group performance status and liver metastases were independent prognostic factors affecting PFS and OS. No new anlotinib-related adverse reactions were identified.
Conclusion
Anlotinib was effective for first-line maintenance and second-line treatment, and the chemotherapy combination regimen was superior to monotherapy when applied as second-line treatment. However, this trend was not observed in third-line and above therapy.
Mechanical thrombectomy (MT) has been proven as an effective and safe therapy for patients with acute ischemic stroke from large vessel occlusion. However, there is still a controversial topic about ...post-procedural management including blood pressure (BP).
A total of 294 patients who received MT in Second Affiliated Hospital of Soochow University from April 2017 to September 2021 were included consecutively. The association of blood pressure parameters (BPV and hypotension time) with poor functional outcome was evaluated using logistic regression models. Meanwhile, the effects of BP parameters on mortality was analyzed using cox proportional hazards regression models. Furthermore, the corresponding multiplicative term was added to the above models to study the interaction between BP parameters and CS.
Two hundred ninety four patients were included finally. The mean age was 65.5 years. At the 3-month follow-up, 187(61.5%) had poor functional outcome and 70(23.0%) died. Regardless of the CS, BP CV is positively associated with poor outcome. Hypotension time was negatively associated with poor outcome. We conducted a subgroup analysis according to CS. BPV was significantly associated with mortality at 3-month and displayed a trend toward poor outcome for patients with poor CS only. The interaction between SBP CV and CS with respect to mortality after adjusting for confounding factors was statistically significant (P for interaction = 0.025) and the interaction between MAP CV and CS with respect to mortality after multivariate adjustment was also statistically significant (P for interaction = 0.005).
In MT-treated stroke patients, higher BPV in the first 72 h is significantly associated with poor functional outcome and mortality at 3-month regardless of CS. This association was also found for hypotension time. Further analysis showed CS modified the association between BPV and clinical prognosis. BPV displayed a trend toward poor outcome for patients with poor CS.
Stroke, including ischemic and hemorrhagic stroke, causes massive cell death in the brain, which is followed by secondary inflammatory injury initiated by disease-associated molecular patterns ...released from dead cells. Phagocytosis, a cellular process of engulfment and digestion of dead cells, promotes the resolution of inflammation and repair following stroke. However, professional or non-professional phagocytes also phagocytose stressed but viable cells in the brain or excessively phagocytose myelin sheaths or prune synapses, consequently exacerbating brain injury and impairing repair following stroke. Phagocytosis includes the smell, eating and digestion phases. Notably, efficient phagocytosis critically depends on phagocyte capacity to take up dead cells continually due to the limited number of phagocytes vs. dead cells after injury. Moreover, phenotypic polarization of phagocytes occurring after phagocytosis is also essential to the proresolving and prorepair properties of phagocytosis. Much has been learned about the molecular signals and regulatory mechanisms governing the sense and recognition of dead cells by phagocytes during the smell and eating phase following stroke. However, some key areas remain extremely understudied, including the mechanisms involved in digestion regulation, continual phagocytosis and phagocytosis-induced phenotypic switching following stroke. Here, we summarize new discoveries related to the molecular mechanisms and multifaceted effects of phagocytosis on brain injury and repair following stroke and highlight the knowledge gaps in poststroke phagocytosis. We suggest that advancing the understanding of poststroke phagocytosis will help identify more biological targets for stroke treatment.
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