Objective:To investigate the mechanism of learning and memory impairment of apolipoprotein E -/- ( ApoE-/-) mice after transient global cerebral ischemia by diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). Methods:Ten-week-old C57BL/6(WT) mice and ApoE-/- mice were randomly divided into WT sham-operated group ( n=8), WT 7 d group ( n=12) and WT 30 d group ( n=12), and ApoE-/- sham-operated ( n=8), ApoE-/- 7 d group ( n=12) and ApoE-/- 30 d group ( n=12). The mice in the WT 7 d group, WT 30 d group, ApoE-/- 7 d group, and ApoE-/- 30 d group received bilateral common carotid artery ischemia-reperfusion injury, while mice in the WT sham-operated group and ApoE sham-operated group only stripped the blood vessels without ligation. On the 7 th and 30 th d of modeling, Morrris water maze test was employed to detect the learning and memory abilities of these mice; DTI was used to detect the fractional anisotropy (FA) values in the bilateral hippocampus of mice, and MRS was used to detect the contents of choline complex (Cho) and N-acetylaspartate (NAA) in the bilateral hippocampus of mice. Results:(1) On 2 nd, 3 rd, and 4 th d of water maze experiment, the escape latency of mice in ApoE-/- 7 d group was significantly prolonged as compared with that in the ApoE-/- sham-operated group and WT 7 d group ( P<0.05); since the 3 rd d of water maze experiment, the escape latency of mice in ApoE-/- 30 d group was significantly prolonged as compared with that in WT 30 d group ( P<0.05). The number of times crossing platform in ApoE-/- 7 d group was significantly smaller than that in WT 7 d group, and the residence time in the third quadrant was significantly shorter ( P<0.05); the number of times crossing platform in ApoE-/- 30 d group were significantly smaller as compared with that in the WT 30 d group, and the residence time in the third quadrant was significantly shortened ( P<0.05). (2) DTI results showed that there was no significant difference in bilateral hippocampal FA values between ApoE-/- 7 d group and WT 7 d group ( P>0.05); the bilateral hippocampal FA values of mice in the ApoE-/- 30 d group were statistically lower than those in WT 30 d group ( P<0.05). (3) MRS results showed that the relative contents of hippocampal Cho and NAA in the ApoE-/- 7 d group were significantly lower than those in the WT 7 d group, and the relative contents of hippocampal Cho and NAA in the ApoE-/- 30 d group were significantly lower than those in the WT 30 d group ( P<0.05). Conclusion:ApoE-/- mice have poor learning and memory abilities after transient global cerebral ischemic injury, whose mechanism is closely related to the damage of hippocampal white matter fibers and abnormal metabolism of nerve cells.

Objective:To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT.Methods:This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model.Results:A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) μg/L vs. 158 (68, 379) μg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group ( P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF ( OR=1.08, 95% CI 1.02-1.15, P=0.008), decreased LVESD ( OR=1.07, 95% CI 1.01-1.12, P=0.013), and increased D-dimer levels ( OR=5.40, 95% CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95% CI 0.710-0.876, P<0.001). Conclusion:Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.

ObjectiveTo investigate the effects of Congrong Zonggan capsules （CRZG） on cognitive impairment in the Alzheimer's disease （AD） model of mice and its related mechanisms. MethodsSPF grade 4-week-old 5×FAD mice were divided into a model group， low-dose CRZG （0.819 g·kg^-1） and high-dose CRZG （1.638 g·kg^-1） groups， and Donepezilepezil hydrochloride group （2 mg·kg^-1）， with eight mice in each group. Eight C57 mice with the same background were set as the normal group. After one week of adaptive feeding， mice were orally administered continuously for six months. On the 5th month of drug administration， Y maze， new object recognition， and Morris water maze tests were conducted separately. After administration， mouse brain tissue was taken， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in brain tissue were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the expression of small glial cell markers Iba1， astrocyte markers GFAP， and amyloid protein 1-42 （Aβ_1-42） in the hippocampus of the brain tissue. The hematoxylin-eosin （HE） staining was used to detect pathological changes in the hippocampus of brain tissue. Western blot was used to detect the expression of nuclear factor-κB （NF-κB） p65， NOD-like receptor protein 3 （NLRP3）， cleaved Caspase-1， apoptosis-associated speck-like protein containing a CARD （ASC）， and other proteins in the brain tissue. ResultsCompared with those in the normal group， the mice in the model group had obvious cognitive impairment. The spontaneous alternation rate of the Y maze was decreased， and the discrimination index of novel object recognition was decreased significantly （P<0.01）. The escape latency in the water maze was shortened significantly （P<0.01）. The contents of IL-6 and TNF-α in brain tissue were increased. The fluorescence levels of Iba1 and Aβ_1-42 in the hippocampus were significantly increased （P<0.01）. There was a significant increase in neuronal lesions， neuronal atrophy， loose arrangement of tissue structure， and abnormal erythrocyte aggregation in the hippocampus. The protein expressions of p-NF-κB p65/NF-κB p65， cleaved Caspase-1， ASC， IL-6， and IL-1β were significantly increased （P<0.05， P<0.01）. Compared with the model group， the spontaneous alternation rate and discrimination index of the high-dose CRZG group were increased significantly （P<0.01）， and the escape latency was shortened significantly （P<0.05， P<0.01）. The content of IL-6 decreased in the brain， and that of TNF-α dropped significantly （P<0.01）. The expression of Iba1 protein and Aβ_1-42 in the hippocampus decreased significantly （P<0.05， P<0.01）. The hippocampal neurons were densely arranged， and the pyramidal nuclei were clear and centered. The abnormal aggregation of red blood cells was alleviated. The value of p-NF-κB/NF-κB proteins and the expression of ASC， cleaved Caspase-1， IL-6， and IL-1β were significantly decreased （P<0.05， P<0.01）. ConclusionCRZG can effectively improve cognitive impairment in 5×FAD mice with Alzheimer's disease， and its mechanism may be related to the regulation of the NF-κB/NLRP3 pathway to reduce the abnormal activation of microglia and inhibit neuroinflammation.