Objective:To investigate clinical significance and related factors of magnetic resonance hyperintense vessel sign (HVS).Methods:The clinical data and related imaging parameters of 109 patients with acute anterior circulation occlusion cerebral infarction, who admitted to Northern Theater Command General Hospital of People′s Liberation Army from April 2017 to August 2019, were analyzed retrospectively. Brain magnetic resonance imaging (MRI) examinations including fluid attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI) and three dimensional time of flight magnetic resonance angiography (3D TOF MRA) sequences within 24 hours of onset were performed. According to the distribution range of HVS in FLAIR sequence, the patients were divided into four grades (0, 1, 2 and 3), grades 0 and 1 belonging to HVS low grade group, and grades 2 and 3 HVS high grade group. Univariate and multivariate analyses were made to explore related factors of HVS. Fifty-two patients who completed baseline CT within six hours of onset before MRI examination were performed CT-Alberta Stroke Program Early CT Score (CT-ASPECTS) and DWI-Alberta Stroke Program Early CT Score (DWI-ASPECTS).The difference between CT-ASPECTS and DWI-ASPECTS was calculated. When the difference of ASPECTS ≤1, they were categorized as ASPECTS unchanged group (AN group); when the difference of ASPECTS>1, they were categorized as ASPECTS changed group (AY group). These two groups were compared to explore whether there was any difference in HVS grade, and Spearman correlation analysis was performed to investigate the relationship between HVS grade and the difference of ASPECTS.Results:The difference of hyperlipidemia, TOAST classification (large artery atherosclerosis (LAA), other etiology (SOE) or undetermined etiology (SUE)) and Willis circle classification (types Ⅰ, Ⅱ, Ⅲ and Ⅳ) between HVS groups were remarkable (58.6% (34/58) vs 37.3% (19/51), χ2=4.959, P=0.026; 23/5/23 vs 43/1/14, P=0.004; 3/14/12/22 vs 7/29/14/8, χ2=13.124, P=0.004). Other clinical factors and the locations of vessel occlusion did not show significant difference ( P>0.05). Multivariate Logistic regression analysis indicated that LAA in TOAST classification (LAA vs SOE or SUE, OR=3.054, 95% CI1.257-7.422, P=0.014), Willis circle type Ⅰ (type Ⅰ vs type Ⅳ, OR=5.494, 95% CI1.074-28.091, P=0.041), and type Ⅱ (type Ⅱ vs type Ⅳ, OR=5.571, 95% CI1.895-16.372, P=0.002) were independent related factors to stimulate wide distribution of HVS. The grades of HVS were significantly different between the AN group and the AY group (1/15 vs18/18, χ2=9.114, P=0.002). Spearman correlation analysis showed that HVS grade was negatively correlated with the difference of ASPECTS ( r=-0.573, P<0.001). Conclusions:Both TOAST and Willis circle classifications are crucial factors affecting HVS distribution. HVS distribution range reflects the status of collateral compensatory. Recognizing HVS may help to evaluate the progress of early cerebral infarction volume.

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC₅₀ = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.