Association of plaque characteristics with long-term stroke recurrence in patients with intracranial atherosclerotic disease: a 3D high-resolution MRI-based cohort study.

OBJECTIVES: To evaluate the predictive ability of plaque characteristics for long-term stroke recurrence among patients with symptomatic intracranial atherosclerotic disease (ICAD). METHODS: This cohort study included 132 patients with acute ischemic stroke (AIS) attributed to ICAD who were recruited between July 2017 and December 2020 and followed until stroke recurrence or December 2021. Plaque surface irregularity, degree of stenosis, plaque burden, remodeling ratio, enhancement ratio, and intraplaque hemorrhage were assessed with 3-dimensional high-resolution magnetic resonance vessel wall imaging (3D HR-MRI). Data were analyzed using Cox models, receiver operating characteristic (ROC) curves, and Kaplan-Meier survival analysis. RESULTS: Of the 132 patients, during a median follow-up of 2.8 years, stroke recurrence occurred in 35 patients. The multivariable-adjusted hazard ratio (95% confidence interval) of stroke recurrence was 3.15 (1.34-7.42) per 10% increase in plaque burden and 2.17 (1.27-3.70) for enhancement ratio. The area under the curve (AUC) to predict stroke recurrence was 0.725 (95% CI 0.629-0.822) for plaque burden, 0.692 (95% CI 0.593-0.792) for enhancement ratio, and only 0.595 (95% CI 0.492-0.699) for the Essen stroke risk score. The Kaplan-Meier survival analysis further demonstrated significant differences in survival of free recurrent stroke between patients with plaque burden or enhancement ratio below and above the optimum cut-offs (both p < 0.001). CONCLUSION: Higher plaque burden and enhancement ratio are independent risk factors for long-term stroke recurrence among patients with symptomatic ICAD, and valuable imaging markers for predicting and stratifying risk of stroke recurrence. CLINICAL RELEVANCE STATEMENT: In patients with symptomatic ICAD, the results of this high-resolution magnetic resonance vessel wall imaging study have potential implications for optimal management of intracranial plaques and secondary prevention of stroke recurrence based on plaque burden and enhancement ratio. KEY POINTS: • Identification of intracranial plaque characteristics responsible for stroke recurrence is essential to preventing stroke recurrence in patients with symptomatic intracranial atherosclerotic disease. • Higher plaque burden and enhancement ratio are independent risk factors for stroke recurrence. • Plaque burden and enhancement ratio are valuable imaging markers in the prediction and stratification of the risk of stroke recurrence.

FLAIR vascular hyperintensity combined with asymmetrical prominent veins in acute anterior circulation ischemic stroke: prediction of collateral circulation and clinical outcome.

BACKGROUND: To investigate the value of fluid-attenuated inversion recovery vascular hyperintensity (FVH) within asymmetrical prominent veins sign (APVS) on susceptibility-weighted imaging predicting collateral circulation and prognosis in patients with acute anterior circulation ischemic stroke. METHOD: Patients with severe stenosis or occlusion of ICA or MCA M1, who underwent MRI within 72 h from stroke onset were reviewed. The Alberta Stroke Program Early CT Score was used to evaluate the volume of infarction on DWI, the degree of FVH and APVS. Spearman correlation analysis was used to evaluate the correlation between FVH and APVS. All patients were divided into the good prognosis group and the poor prognosis group according to the score of the modified ranking scale (mRS) 90 days after the stroke. Logistic regression analysis was used to explore the relationship between FVH and APVS and functional prognosis, while receiver operating characteristic (ROC) curves were plotted to assess the value of FVH and APVS in predicting prognosis. RESULTS: Spearman correlation analysis revealed moderate positive correlations between FVH and APVS (r = 0.586, P < 0.001). The poor prognosis group had a higher rate of a history of atrial fibrillation, a larger cerebral infarction volume, a higher NIHSS score at admission, and a higher FVH and APVS score compared with the good prognosis group (all P < 0.05). A further logistic regression indicated that the NIHSS score, cerebral infarction volume, FVH and APVS were independent risk factors for a poor functional prognosis. In terms of FVH, APVS, alone and their combination for the diagnosis of poor prognosis, the sensitivity, specificity, area under the ROC curve (AUC), and 95% confidence interval (CI) were 86.8%, 83.3%, 0.899 (95% CI 0.830-0.968); 60.5%, 93.7%, 0.818 (95% CI 0.723-0.912); 86.8%, 89.6%, 0.921 (95% CI 0.860-0.981), respectively. CONCLUSION: The presence of FVH and APVS can provide a comprehensive assessment of collateral circulation from the perspective of veins and arteries, and the correlation between the two is positively correlated. Both of them were independent risk factors for poor prognosis, their combination is complementary and can improve the predictive value.

Identification of DLL3-related genes affecting the prognosis of patients with colon adenocarcinoma.

Background: Delta-like ligand 3 (DLL3) is one of the NOTCH family of ligands, which plays a pro- or anti-carcinogenic role in some cancers. But the role of DLL3 in colon adenocarcinoma (COAD) has not been studied in depth. Materials and methods: First, we used Kaplan-Meier (K-M) curve to evaluate the effect of DLL3 on the prognosis of COAD in The Cancer Genome Atlas (TCGA), which was further validated in clinical samples for immunohistochemistry. Then we screened for differentially expressed genes (DEGs) of DLL3 by analyzing datasets of COAD samples from Gene Expression Omnibus (GEO) and TCGA. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and Gene Set Enrichment Analysis (GSEA) were conducted to explore the underlying mechanisms of DLL3-related in the development and prognosis of COAD. On the basis of DLL3-related signature genes, a prognostic model and a nomogram were constructed. Finally, CIBERSORT was applied to assess the proportion of immune cell types in COAD sample. Results: Survival analysis showed a significant difference in overall survival between high- and low-expression group (p = 0.0092), with COAD patients in the high-group having poorer 5-year survival rate. Gene functional enrichment analysis revealed that DLL3-related DEGs were mainly enriched in tumor- and immunity-related signaling pathways, containing AMPK pathway and mitophagy-animal. The comparison of COAD tumor and normal, DLL3 high- and low-expression groups by GSEA found that AMPK signaling pathway and mitophagy-animal were inhibited. Nomogram constructed from DLL3-related signature genes had a good predictive effect on the prognosis of COAD. We found the highest correlation between DLL3 and interstitial dendritic cell (iDC), natural killer (NK) cell and Interstitial dendritic cell (Tem). DLL3 was also revealed to be diagnostic for COAD. In clinical sample, we identified higher DLL3 expression in colon cancer tissue than in adjacent control (p < 0.0001) and in metastasis than in primary lesion (p = 0.0056). DLL3 expression was associated with stage and high DLL3 expression was observed to predict poorer overall survival (p = 0.004). Conclusion: It suggested that DLL3 may offer prognostic value and therapeutic potential for individualized treatment of COAD, and that it may has a diagnostic role in COAD.

Vascular calcification in CKD: New insights into its mechanisms.

Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) and contributes to an increased risk of cardiovascular morbidity and mortality. However, effective therapies are still unavailable at present. It has been well established that VC associated with CKD is not a passive process of calcium phosphate deposition, but an actively regulated and cell-mediated process that shares many similarities with bone formation. Additionally, numerous studies have suggested that CKD patients have specific risk factors and contributors to the development of VC, such as hyperphosphatemia, uremic toxins, oxidative stress and inflammation. Although research efforts in the past decade have greatly improved our knowledge of the multiple factors and mechanisms involved in CKD-related VC, many questions remain unanswered. Moreover, studies from the past decade have demonstrated that epigenetic modifications abnormalities, such as DNA methylation, histone modifications and noncoding RNAs, play an important role in the regulation of VC. This review seeks to provide an overview of the pathophysiological and molecular mechanisms of VC associated with CKD, mainly focusing on the involvement of epigenetic modifications in the initiation and progression of uremic VC, with the aim to develop promising therapies for CKD-related cardiovascular events in the future.

T cells and their products in diabetic kidney disease.

Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease and has gradually become a public health problem worldwide. DKD is increasingly recognized as a comprehensive inflammatory disease that is largely regulated by T cells. Given the pivotal role of T cells and T cells-producing cytokines in DKD, we summarized recent advances concerning T cells in the progression of type 2 diabetic nephropathy and provided a novel perspective of immune-related factors in diabetes. Specific emphasis is placed on the classification of T cells, process of T cell recruitment, function of T cells in the development of diabetic kidney damage, and potential treatments and therapeutic strategies involving T cells.

Prognostic value of susceptibility-weighted imaging of prominent veins in acute ischemic stroke: A systematic review and meta-analysis.

Background: The prominent veins sign (PVS) on susceptibility-weighted imaging (SWI) has been suggested to be related to the prognosis of patients with acute ischemic stroke (AIS). This meta-analysis aims to clarify the association between PVS and the prognosis of patients with AIS. Methods: This meta-analysis was registered in PROSPERO (no. CRD42022343795). We performed systematic research in PubMed, Web of Science, EMBASE, and Cochrane Library databases for studies investigating the prognostic value of PVS. Based on the enrolled studies, patients were divided into two groups as follows: those with PVS cohort and those without PVS cohort. Outcomes were unfavorable functional outcome, early neurological deterioration (END), and hemorrhagic transformation (HT). The random-effects models were used for the meta-analytical pooled. Heterogeneity was estimated using Cochran's Q-test and I 2 value. Subgroup and sensitivity analyses were also performed to explore the potential sources of heterogeneity. Publication bias was assessed with funnel plots and using Begger's and Egger's tests. Results: A total of 19 studies with 1,867 patients were included. PVS was correlated with an unfavorable functional outcome in patients with AIS (risk ratio [RR] 1.61, 95% CI 1.28-2.02), especially in those receiving recanalization therapy (RR 2.00, 95% CI 1.52-2.63), but not in those treated conservatively (RR 1.33, 95% CI 0.87-2.04). Moreover, PVS was related to END (RR 2.77, 95% CI 2.21-3.46), while without an increased risk of HT (RR 0.97, 95% CI 0.64-1.47). Conclusion: PVS was associated with an unfavorable prognosis of patients with AIS and increased the risk of END, while not correlated with an increased risk of HT. PVS might be useful for predicting functional outcomes of patients with AIS as a novel imaging maker. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022343795.

Improved Coarse-Grained Model for Nanoparticles Based on the Martini Force Field and Its Application in Molecular Dynamics Simulation on Gel Ink.

Research on the dispersion and stability of nanoparticles in liquid media is one of the key subjects for nanomaterial utilization. In consideration of the preponderance of coarse-grained (CG) molecular dynamics (MD) simulation in following and understanding the structure and dynamics on the nanoscale, an improved CG model for nanoparticles based on the Martini force field is established to facilitate the more extensive applications of this simulation method and further studies on complex nanoparticle liquid systems. Gel ink is selected as the liquid system for nanoparticles to validate the improved CG model on the one hand and introduce the CGMD simulation method into the studies of this system on the other. The calculation shows that the improved model can provide relatively precise results and has good computational stability. The effect mechanisms of the thickener and disperser on the carbon black nanoparticle are similar, namely the result of a delicate balance between the interaction of the thickener/disperser with the carbon black nanoparticle and the interaction of the thickener and disperser with each other. Furthermore, the phase assimilating effect of disperser molecules is key for separating the agglomerated carbon black nanoparticles; thereafter, the space steric hindrance effect and the electrostatic hindrance effect play main roles in maintaining the dispersion of carbon black nanoparticles.

Two case reports of chorea-acanthocytosis and review of literature.

BACKGROUND: Chorea-acanthocytosis (ChAc), as the most common subtype of neuroacanthocytosis syndrome, is characterized by the presence of acanthocytes and neurological symptoms. It is thought to be caused by the VPS13A (vacuolar protein sorting-associated protein 13A) mutations. This article reports two confirmed cases of ChAc and summarizes some suggestive features, which provide direction for the diagnosis and treatment of acanthocytosis in the future. CASE PRESENTATION: Here, we present two cases of ChAc diagnosed based on typical clinical symptoms, neuroimaging features, genetic findings of VPS13A, and response to the symptomatic treatment. CONCLUSIONS: Chorea-acanthocytosis is a rare neurodegenerative disease with various early clinical manifestations. The final diagnosis of the ChAc can be established by either genetic analysis or protein expression by Western blotting. Supportive treatments and nursing are helpful to improve the quality of the patient's life. Nevertheless, it is imperative to investigate the impact of neuroimaging and neuropathological diagnosis in a larger group of ChAc in future studies.

ENT1 inhibition attenuates epileptic seizure severity via regulation of glutamatergic neurotransmission.

Type 1 equilibrative nucleoside transporter (ENT1) promotes glutamate release by inhibition of adenosine signaling. However, whether ENT1 plays a role in epileptic seizure that involves elevated glutamatergic neurotransmission is unknown. Here, we report that both seizure rats and patients show increased expression of ENT1. Intrahippocampal injection of a specific inhibitor of ENT1, nitrobenzylthioinosine (NBTI), attenuates seizure severity and prolongs onset latency. In order to examine whether NBTI would be effective as antiepileptic after peripheral application, we injected NBTI intraperitoneally, and the results were similar to those obtained after intrahippocampal injection. NBTI administration leads to suppressed neuronal firing in seizure rats. In addition, increased mEPSC in seizure are inhibited by NBTI. Finally, NBTI results in deactivation of phosphorylated cAMP-response element-binding protein in the seizure rats. These results indicate that ENT1 plays an important role in the development of seizure. Inhibition of ENT1 might provide a novel therapeutic approach toward the control of epileptic seizure.

5-HT6 Receptor Recruitment of mTOR Modulates Seizure Activity in Epilepsy.

Approximately 30% of epilepsy cases are refractory to current pharmacological treatments. Thus, novel therapeutic approaches that prevent or reverse the molecular and cellular mechanisms of epilepsy are required. 5-HT6 receptor (HTR6) blockade can modulate multiple neurotransmitter systems, and HTR6 may be a potential therapeutic treatment for neurological diseases, including epilepsy. Here, we investigated the role of HTR6 in epilepsy. We detected HTR6 expression both in human epileptic tissues and the pilocarpine rat model by western blotting. We observed behavioral changes after administration of pilocarpine in rats pretreated with a selective HTR6 antagonist, SB-399885, and recorded the electrophysiological index in the pilocarpine rat model pre- or posttreated with SB-399885 by electroencephalogram (EEG) and whole-cell clamp. We measured the activity of mammalian target of rapamycin (mTOR) in the pilocarpine rat model pretreated with the mTOR-specific inhibitor, rapamycin, and SB-399885 using western blotting. We found that HTR6 expression was upregulated in both human tissues and the pilocarpine rat model, and that SB-399885 could suppress epileptic seizures and mTOR activity in epileptic seizures. These results suggest that HTR6 plays an important role in modulating seizure activity and that the blockade of the HTR6/mTOR pathway could be a potential therapeutic target for epilepsy treatment.