Differential expression of Semaphorin-7A /CD163-positive macrophages in large artery and cardiogenic stroke.

BACKGROUND: Identification of the causes of stroke of undetermined etiology, specifically cardioembolism (CE) and non-CE causes, can inform treatment planning and prognosis prediction. The objective of this study was to analyze the disparities in thrombus composition, particularly Semaphorin-7A (Sema7A) and CD163, between patients diagnosed with large-artery atherosclerosis (LAA) and those with CE, and to investigate their potential association with prognosis. METHODS: Thrombi were collected from patients who underwent mechanical thrombectomy at two hospitals. The patients were categorized into two groups: LAA and CE. We compared the levels of Sema7A and CD163 between these groups and analyzed their relationships with stroke severity, hemorrhagic transformation and prognosis. RESULTS: The study involved a total of 67 patients. Sema7A expression was found to be significantly higher in the CE group compared to LAA (p < 0.001). Conversely, no statistically significant differences were observed for CD163 between the groups. The presence of Sema7A/CD163 did not show any associations with stroke severity or hemorrhagic transformation (all p > 0.05). However, both Sema7A (OR, 2.017; 95% CI, 1.301-3.518; p = 0.005) and CD163 (OR, 2.283; 95% CI, 1.252-5.724; p = 0.03) were associated with the poor prognosis for stroke, after adjusting for stroke severity. CONCLUSION: This study highlights that CE thrombi exhibited higher levels of Sema7A expression compared to LAA thrombi. Moreover, we found a positive correlation between Sema7A/CD163 levels and the poor prognosis of patients with acute ischemic stroke.

Effect of sacubitril/valsartan on brain natriuretic peptide level and prognosis of acute cerebral infarction.

BACKGROUND AND PURPOSE: Previous studies demonstrated that elevated brain natriuretic peptide (BNP) level is associated with adverse clinical outcomes of acute cerebral infarction (ACI). Researchers hypothesized that BNP might be a potential neuroprotective factor against cerebral ischemia because of the antagonistic effect of the natriuretic peptide system on the renin-angiotensin system and regulation of cardiovascular homeostasis. However, whether decreasing the BNP level can improve the prognosis of ACI has not been studied yet. The main effect of sacubitril/valsartan is to enhance the natriuretic peptide system. We investigated whether the intervention of plasma BNP levels with sacubitril/valsartan could improve the prognosis of patients with ACI. METHODS: In a randomized, controlled, parallel-group trial of patients with ACI within 48 hours of symptom onset and need for antihypertensive therapy, patients have randomized within 24 hours to sacubitril/valsartan 200mg once daily (the intervention group) or to conventional medical medication (the control group). The primary outcome was a change in plasma BNP levels before and after sacubitril/valsartan administration. The secondary outcomes included plasma levels of brain-derived neurotrophic factor (BDNF), Corin and neprilysin (NEP) before and after medication, the modified Rankin scale, and the National Institutes of Health Stroke Scale (at onset, at discharge, 30 days, and 90 days after discharge). RESULTS: We evaluated 80 eligible patients admitted to the Stroke Center of Lianyungang Second People's Hospital between 1st May, 2021 and 31st June, 2022. Except for 28 patients excluded before randomization and 14 patients who did not meet the criteria or dropped out or lost to follow-up during the trial, the remaining 38 patients (intervention group: 17, control group: 21) had well-balanced baseline features. In this trial, we found that plasma BNP levels (P = 0.003) decreased and NEP levels (P = 0.006) increased in enrolled patients after treatment with sacubitril/valsartan. There were no differences in plasma BDNF and Corin levels between the two groups. Furthermore, no difference in functional prognosis was observed between the two groups (all P values>0.05). CONCLUSIONS: Sacubitril/valsartan reduced endogenous plasma BNP levels in patients with ACI and did not affect their short-term prognosis.

Establishment of a dynamic nomogram including thyroid function for predicting the prognosis of acute ischemic stroke with standardized treatment.

Purpose: Many patients with acute ischemic stroke (AIS) cannot undergo thrombolysis or thrombectomy because they have missed the time window or do not meet the treatment criteria. In addition, there is a lack of an available tool to predict the prognosis of patients with standardized treatment. This study aimed to develop a dynamic nomogram to predict the 3-month poor outcomes in patients with AIS. Methods: This was a retrospective multicenter study. We collected the clinical data of patients with AIS who underwent standardized treatment at the First People's Hospital of Lianyungang from 1 October 2019 to 31 December 2021 and at the Second People's Hospital of Lianyungang from 1 January 2022 to 17 July 2022. Baseline demographic, clinical, and laboratory information of patients were recorded. The outcome was the 3-month modified Rankin Scale (mRS) score. The least absolute shrinkage and selection operator regression were used to select the optimal predictive factors. Multiple logistic regression was performed to establish the nomogram. A decision curve analysis (DCA) was applied to assess the clinical benefit of the nomogram. The calibration and discrimination properties of the nomogram were validated by calibration plots and the concordance index. Results: A total of 823 eligible patients were enrolled. The final model included gender (male; OR 0.555; 95% CI, 0.378-0.813), systolic blood pressure (SBP; OR 1.006; 95% CI, 0.996-1.016), free triiodothyronine (FT3; OR 0.841; 95% CI, 0.629-1.124), National Institutes of Health stroke scale (NIHSS; OR 18.074; 95% CI, 12.264-27.054), Trial of Org 10172 in Acute Stroke Treatment (TOAST; cardioembolic (OR 0.736; 95% CI, 0.396-1.36); and other subtypes (OR 0.398; 95% CI, 0.257-0.609). The nomogram showed good calibration and discrimination (C-index, 0.858; 95% CI, 0.830-0.886). DCA confirmed the clinical usefulness of the model. The dynamic nomogram can be obtained at the website: predict model (90-day prognosis of AIS patients). Conclusion: We established a dynamic nomogram based on gender, SBP, FT3, NIHSS, and TOAST, which calculated the probability of 90-day poor prognosis in AIS patients with standardized treatment.

Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease.

Background and purpose: The prevalence of cerebral small vessel disease (CSVD) is increasing due to the accelerating global aging process, resulting in a substantial burden on all countries, as cognitive dysfunction associated with CSVD is also on the rise. Clock genes have a significant impact on cognitive decline and dementia. Furthermore, the pattern of DNA methylation in clock genes is strongly associated with cognitive impairment. Thus, the aim of this study was to explore the connection between DNA promoter methylation of PER1 and CRY1 and cognitive dysfunction in patients with CSVD. Methods: We recruited patients with CSVD admitted to the Geriatrics Department of the Lianyungang Second People's Hospital between March 2021 and June 2022. Based on their Mini-Mental State Examination score, patients were categorized into two groups: 65 cases with cognitive dysfunction and 36 cases with normal cognitive function. Clinical data, 24-h ambulatory blood pressure monitoring parameters, and CSVD total load scores were collected. Moreover, we employed methylation-specific PCR to analyze the peripheral blood promoter methylation levels of clock genes PER1 and CRY1 in all CSVD patients who were enrolled. Finally, we used binary logistic regression models to assess the association between the promoter methylation of clock genes (PER1 and CRY1) and cognitive dysfunction in patients with CSVD. Results: (1) A total of 101 individuals with CSVD were included in this study. There were no statistical differences between the two groups in baseline clinical data except MMSE and AD8 scores. (2) After B/H correction, the promoter methylation rate of PER1 was higher in the cognitive dysfunction group than that in the normal group, and the difference was statistically significant (adjusted p < 0.001). (3) There was no significant correlation between the promoter methylation rates of PER1 and CRY1 in peripheral blood and circadian rhythm of blood pressure (p > 0.05). (4) Binary logistic regression models showed that the influence of promoter methylation of PER1 and CRY1 on cognitive dysfunction were statistically significant in Model 1 (p < 0.001; p = 0.025), and it still existed after adjusting for confounding factors in Model 2. Patients with the promoter methylation of PER1 gene (OR = 16.565, 95%CI, 4.057-67.628; p < 0.001) and the promoter methylation of CRY1 gene (OR = 6.017, 95%CI, 1.290-28.069; p = 0.022) were at greater risk of cognitive dysfunction compared with those with unmethylated promoters of corresponding genes in Model 2. Conclusion: The promoter methylation rate of PER1 gene was higher in the cognitive dysfunction group among CSVD patients. And the hypermethylation of the promoters of clock genes PER1 and CRY1 may be involved in affecting cognitive dysfunction in patients with CSVD.

Thyroid hormone levels paradox in acute ischemic stroke.

Objective: Accumulating evidence has suggested that thyroid hormone levels affect the prognosis of acute ischemic stroke (AIS), but the results have been inconsistent. Methods: Basic data, neural scale scores, thyroid hormone levels, and other laboratory examination data of AIS patients were collected. The patients were divided into excellent and poor prognosis group at discharge and 90 days after discharge. Logistic regression models were applied to evaluate the relationship between thyroid hormone levels and prognosis. A subgroup analysis was performed based on stroke severity. Results: A number of 441 AIS patients were included in this study. Those in the poor prognosis group were older, with higher blood sugar levels, higher free thyroxine (FT4) levels, and severe stroke (all p < 0.05) at baseline. Free thyroxine (FT4) showed a predictive value (all p < 0.05) for prognosis in the model adjusted for age, gender, systolic pressure, and glucose level. However, after adjustment for types and severity of stroke, FT4 showed insignificant associations. In the severe subgroup at discharge, the change in FT4 was statistically significant (p = 0.015), odds ratio (95% confidence interval) = 1.394 (1.068-1.820) but not in the other subgroups. Conclusions: High-normal FT4 serum levels in patients with severe stroke receiving conservative medical treatment at admission may indicate a worse short-term prognosis.

Absence of fluctuation and inverted circadian rhythm of blood pressure increase the risk of cognitive dysfunction in cerebral small vessel disease patients.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a common cause of stroke and senile vascular cognitive impairment, imposing a heavy burden on public health care systems worldwide. Hypertension and 24-hour blood pressure variability (BPV), known to be significant risk factors for cognitive dysfunction, have been found to be associated with cognitive function in CSVD patients in previous studies. However, as a derived part of BPV, there are few studies on the relationship between circadian rhythm of blood pressure and cognitive dysfunction in CSVD patients, and the relationship between them is still unclear. Thus, this study aimed to investigate whether the disturbance of circadian rhythm of blood pressure can affect the cognitive function of patients with CSVD. METHODS: A total of 383 CSVD patients hospitalized in the Geriatrics Department of the Lianyungang Second People's Hospital between May 2018 and June 2022 were enrolled in this study. The clinical information and parameters of 24-hour ambulatory blood pressure monitoring were compared between the cognitive dysfunction group (n = 224) and the normal group (n = 159). Finally, a binary logistic regression model was used to assess the relationship between circadian rhythm of blood pressure and cognitive dysfunction in patients with CSVD. RESULTS: (1) Patients in the cognitive dysfunction group were older, had lower blood pressure on admission, and had a greater number of previous cardiovascular and cerebrovascular diseases (P < 0.05). (2) More patients in the cognitive dysfunction group had circadian rhythm abnormalities in blood pressure, especially the non-dipper and reverse-dipper types (P < 0.001). (3) In the elderly, there was a statistical difference in the circadian rhythm of blood pressure between the cognitive dysfunction group and the normal group, but this phenomenon did not exist in the middle-aged. (4) Binary logistic regression analysis showed that after adjusting for confounding factors, the risk of cognitive dysfunction in CSVD patients with non-dipper type was 4.052 times higher than that of dipper type (95% CI, 1.782-9.211; P = 0.001), and reverse-dipper type was 8.002 times higher than those with dipper type (95% CI, 3.367-19.017; P<0.001). CONCLUSIONS: The disturbance of circadian rhythm of blood pressure may affect the cognitive function of patients with CSVD, and the risk of cognitive dysfunction in non-dipper and reverse-dipper types are higher.

Effects of blood glucose and glycosylated hemoglobin levels on intravenous thrombolysis in patients with acute cerebral infarction and type 2 diabetes mellitus.

OBJECTIVE: To investigate the effect of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbAlc.) levels on thrombolytic therapy in patients with acute cerebral infarction and type 2 diabetes mellitus. METHODS: A total of 135 patients with acute cerebral infarction were selected for this study. They were divided into study group (n=70, with acute cerebral infarction & type 2 diabetes mellitus) and control group (n=65, with acute cerebral infarction but no type 2 diabetes mellitus). All patients underwent thrombolysis treatment with Alteplase for injection. The patients were evaluated by the national institutes of health stroke scale (NIHSS) score, the modified Rankin scale (MRS) score and the Barthel index score, such indicators in patients as FPG, HbAlc, triglyceride (TG), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were determined, the fast blood sugar before thrombolysis and the treatment effect after 24h thrombolysis in the observation group were observed and meanwhile the mortality rate in patients after 5 months thrombolysis was analyzed. RESULTS: Compared with before thrombolysis, the indexes of the two groups were significantly improved after thrombolysis, and the improvements of FPG, HbAlc, TG and LDL-C in the control group were better than those in the study group (P<0.05). There was no significant difference between the two groups in the levels of TC and HDL-C after thrombolysis (P>0.05). The 24h MBG, SDBG and MAGE in the study group were higher than those in the control group (P<0.05). In the study group, when the blood glucose was less than 6.0mmol/L before thrombolysis, the lowest effective rate after 24h thrombolysis was 33.3%, and when the blood glucose was ranging from 7.0 to 9.0mmol/L, the highest effective rate after 24h thrombolysis was 73.9%, and with the gradual increase of blood glucose, the effective rate after 24h thrombolysis decreased gradually. Also the effective rate after 24h thrombolysis also decreased gradually with the increase of HbAlc value, it reached the highest value of 64.4% at HbAlc <6.0mmol/Lad the lowest value of 25% at HbAlc >7.0mmol/L. Compared with the control group, the MHSS score and MRS score were higher and the Barthel index after thrombolysis was lower in the study group with the difference being statistically significant (P<0.05). The five months mortality rate after thrombolytic therapy was 12.9% (9/70) in the study group and 10.8% (7/65) in the control group, with no significant difference between the two groups (P=0.316). The incidence of intracranial hemorrhage after thrombolytic therapy was higher in the study group than in the control group, but the difference was not statistically significant (P>0.05), however there was significant difference between the two groups in revascularization and prognosis (P<0.05). CONCLUSION: The level of HbAlc affected the curative efficacy, the higher the level, the poorer the efficacy and to control the blood glucose within a certain range before thrombolysis was beneficial to enhance the effect of static thrombolysis.