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Objective:To explore independent predictors for poor outcome at 3 months in elderly patients with acute cerebral infarction(ACI)treated with intravenous thrombolysis(IVT), and to develop a nomogram-based predictive model.Methods:This was a retrospective cohort study.Clinical, laboratory and imaging data of 346 elderly patients with ACI treated with IVT from January 2016 to April 2021 in our hospital were collected.Poor outcome was defined as a modified Rankin Scale(mRS)score >2 at 3 months after the stroke.Logistic regression analysis was used to screen for independent factors predicting poor outcome in elderly ACI patients treated with IVT, and a corresponding nomogram model was developed using the R software.The ROC curve, calibration plots and decision curve analysis were used to evaluate discrimination, calibration and clinical application value of the nomogram model.Results:Among 346 candidates, 109 developed a poor outcome, representing a rate of 31.5%.Logistic regression analysis showed that symptomatic hemorrhagic transformation( OR=15.647, 95% CI: 8.913-27.454), stroke severity(moderate stroke, OR=3.322, 95% CI: 1.414-7.811; moderate-severe stroke, OR=8.169, 95% CI: 4.102-16.258; severe stroke, OR=9.653, 95% CI: 5.440-17.121), stroke-associated pneumonia( OR=2.239, 95% CI: 1.134-4.420), and heart failure( OR=2.758, 95% CI: 1.424-5.336)were independent predictors for poor outcome at 3 months in elderly ACI patients treated with intravenous thrombolysis(all P<0.05). With the area under curve(AUC-ROC)value at 0.85(95% CI: 0.80-0.89), the nomogram model, which was composed of the above four predictors, demonstrated good discrimination.On the calibration plot, the mean absolute error was 0.020, indicating that the model had good calibration.Decision curve analysis revealed that the model had good clinical application value. Conclusions:The nomogram model composed of symptomatic hemorrhagic transformation, stroke severity, stroke-associated pneumonia and heart failure may predict poor outcome at 3 months in elderly ACI patients treated with IVT, with high prediction accuracy and high clinical application value.
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Objective:To explore the value of intravascular optical coherence tomography (OCT) in evaluating carotid atherosclerotic stenosis, and compare the morphological characteristics of symptomatic and asymptomatic carotid atherosclerotic plaques.Methods:Patients diagnosed as carotid atherosclerotic stenosis and performed OCT in the Department of Neurology, Jinling Hospital, Medical School of Nanjing University from January 2017 to November 2019 were enrolled retrospectively. Digital subtraction angiography (DSA) and OCT were used to determine the degree of stenosis of the diseased vessels, and the plaque characteristics observed by OCT were recorded. Symptomatic carotid atherosclerotic stenosis is defined as a history of transient ischemic attack, amaurosis fugax, or stroke related to the blood supply area of the diseased vessel within 6 months before the carotid artery examination. The baseline clinical and imaging data of the symptomatic group and the asymptomatic group were compared. Multivariate logistic regression analysis was used to determine the independent risk factors for symptomatic carotid atherosclerotic stenosis. Results:A total of 56 patients were enrolled. DSA and OCT had good consistency in carotid artery diameter measurement ( r=0.93, P<0.001). When the OCT technique was used to evaluate the plaque properties, the consistency of inter-observer ( κ=0.96, P<0.001) and intra-observer ( κ=0.96, P<0.001) was higher. The proportions of patients with type Ⅵ plaque (66.7% vs. 34.5%; P=0.016) and macrophage infiltration (51.9% vs. 24.1%; P=0.032) in the symptomatic group were significantly higher than those in the asymptomatic group, while the proportion of patients with fibrotic plaque was significantly lower than that in the asymptomatic group (40.7% vs. 69.0%; P=0.034). Multivariate logistic regression analysis suggested that type Ⅵ plaques (odds ratio 13.798, 95% confidence interval 1.38-137.675; P=0.025) and macrophage infiltration (odds ratio 5.856, 95% confidence interval 1.405-24.406; P=0.015) were the independent risk factors for symptomatic carotid atherosclerotic stenosis. Conclusions:OCT can be used to evaluate the degree of vascular stenosis and plaque characteristics in patients with carotid atherosclerotic stenosis. The detection rate of complex plaques in patients with symptomatic carotid atherosclerotic stenosis is significantly higher. Type Ⅵ plaque and macrophage infiltration are the independent risk factors for symptomatic carotid atherosclerotic stenosis.
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Objective To investigate the difference between histopathological changes of brain white matter in low-density lipoprotein receptor (LDLR) homozygous mutation rats with hypercholesterolemia and wild-type rats.Methods Thirty LDLR-/-rats and 28 wild-type rats were selected.Plasma cholesterol levels were measured by enzyme-linked immunosorbent assay at 15,18 and 26 weeks old respectively.The axonal structure of the corpus callosum area was observed by transmission electron microscopy.The myelin basic protein (MBP) of the corpus callosum area was quantitatively analyzed by Western blotting.In addition,at 26 weeks old,the myelin sheaths were stained by fast blue staining.The expression level of MBP in white matter was further detected by immunofluorescence staining,and the morphological changes of glial cells were observed.Results Compared with the wild-type rats,the plasma cholesterol concentration in LDLR-/-rats increased significantly,and it could be as high as 3.3 times at 26 weeks.The results of electron microscopy showed that the LDLR-/-rats had axonal injury at 15 weeks and aggravated gradually over time.At 26 weeks,Western blot analysis of the LDLR-/-rats showed that the MBP expression level of the corpus callosum area decreased significantly.Fast blue staining showed loosening of nerve fibers,diffuse vacuole formation,and myelinated nerve fiber loss in the corpus callosum area.In addition,it was also found that the number of oligodendrocytes in LDLR-/-rats was significantly reduced,and large numbers of astrocytes and microglia were activated.Conclusions LDLR-/-rats will have spontaneous hypercholesterolemia.Axonal injury,demyelination,decreased oligodendrocytes,as well as the abnormal activation of astrocytes and microglia are present in the early adult brain white matter area.
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White matter lesion is a major subtype of cerebral small vessel disease. Its pathophysiology and mechanism remain unclear. Because the risk factors often coexist in clinical research, it is difficult to judge the relationship between certain risk factors and white matter injury. Moreover, due to the differences in animal and human brain tissue structure, there is currently a lack of reproducible animal models of white matter lesions. Therefore, establishing a practical animal model and further exploring the pathogenesis and risk factors of white matter lesions from the basic research level is crucial for the preclinical study of the treatment of white matter damage. This article reviews the characteristics, optimization measures, and application prospects of the white matter lesion models.
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Objective To investigate the risk factors for early neurological deterioration (END) in patients with acute middle cerebral artery infarction.Methods From January 2009 to December 2012,81 patients with acute middle cerebral artery infarction completed cerebral angiography admitted to the Department of Neurology,Nanjing General Hospital of Nanjing Military Command were enrolled retrospectively.END was defined as that the National Institutes of Health Stroke Scale (NIHSS) score increased ≥2 or the motor score increased ≥ 1 with in 72 h after admission compared with the baseline score on admission.All the patients were divided into either an END group (26 cases) or a non-END group (55 cases) according to whether the occurrence of END.Univariate factor analysis was used to analyze the differences of the clinical data between the two groups.The grade standard of collateral circulation was assessment with the collateral circulation assessment system of the American Society of Interventional and Therapeutic Neuroradiology/Sociey of Interventional Radiology.Multivariable Logistic regression analysis was used to analyze the risk factors for END after acute middle cerebral artery infarction.Results Compared with the patients in the non-END group,the proportions of age 60 years (65.4％ [17/26] vs.36.4％ [20/55];x2 =5.992,P =0.014),high-sensitivity C-reactive protein level ≥4.0 mg/L (76.9％ [20/26] vs.45.5％ [25/55];x2 =7.080,P =0.008) and diabetes (38.5％ [10/26] vs.16.4％ [9/55],x2 =4.802,P =0.028) in the END group were increased significantly,while the collateral circulation grade was decreased significantly (Z =-3.253,P ＜ 0.01).Multivariable Logistic regression analysis showed that the age ≥60 years (OR,3.412,95 ％ CI 1.075-10.824;P =0.037),high-sensitivity C-reactive protein level ≥ 4.0 mg/L (OR,3.812,95％ CI 1.141-12.740;P =0.030),and collateral circulation grade (OR,2.165,95％ CI 1.241-5.514;P =0.009) were the independent risk factor for END in acute middle cerebral artery infarction.Conclusion The decreased collateral circulation level,age ≥ 60 years and high-sensitivity C-reactive protein≥4.0 mg/L were the independent risk factors for occurring END in acute middle cerebral artery infarction.
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Objective To investigate the protective role of human serum albumin in treatment of monocyte-inducible C-type lectin (Mincle)-associated neuroinflammation in subarachnoid hemorrhage (SAH) rats and its underlying mechanisms.Methods Vascular perforation model was used to induce SAH.Ninety-two male SD rats were randomly assigned to sham (n =23),vehicle (n =23),low-dose albumin (0.63 g/kg,n =23) and high-dose albumin (1.25 g/kg,n =23) groups.Saline and albumin were intravenously injected into rats two hours after surgery.Modified Garcia scale was employed to assess neurological functions.Iba-1 and myeloperoxidase (MPO) staining was used to examine the activation of microglial cells and infiltration of neutrophils.Real-time PCR was applied to determine the changes of IL-1β,inducible nitric oxide synthase,CD11b,monocyte chemoattractant protein-1,cytokine-induced neutrophil chemoattractant-1 and CXC motif chemokine ligand-2 mRNA levels.Co-immunoprecipitation was conducted to assess the binding ability of albumin with Mincle.Immunoblotting was carried out to evaluate protein levels of Minlce,Syk and p-Syk.SAH severity measurement was performed before conductions of all the experiments.Results SAH severity scores were 11.4 ± 1.6,12.8 ±2.5 and 11.2 ±3.2 in the vehicle,low-dose albumin and high-dose albumin groups,respectively,without statistically significant difference among groups (F =0.694,P =0.516).Neurological score was 7.5 ± 2.9 in the vehicle group,while the low-dose albumin (14.6 ± 2.2) and high-dose albumin groups (13.6 ± 2.7) exhibited better neurological perfomance (P ＜ 0.01).Immunostaining showed that albumin significantly inhibited the activation of microglia,and reduced the percentage of MPO positive cells from 20.7％ ± 1.9％ in the vehicle group to 12.1％ ±2.1％ in the low-dose albumin group and 9.8％ ±0.9％ in the high-dose albunin group (F =32.216,P =0.001).mRNA levels of pro-inflammatory cytokines and chemotactic factors were also suppressed by albumin (P ＜ 0.05).The results of co-immunoprecipitation displayed that albumin could directly bind Mincle and disrupt the association between Mincle and SAP130.Immunoblotting demonstrated that albumin depressed the protein levels of Mincle,Syk and p-Syk.Conclusion Human serum albumin can inhibit Mincle/Syk-induced neuroinflammation via directly binding Mincle receptor in SAH rats.