Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

Stroke is a critical health issue in China, and carotid artery stenosis and plaque play key roles in its prevalence. Despite the acknowledged significance of this condition, detailed information regarding the prevalence of carotid artery stenosis and plaque across the Chinese population has been scarce. This study analyzed data from the China Stroke High-risk Population Screening and Intervention Program for 2020-2021, focusing on 194 878 Chinese adults aged 40 years and above. It assessed the prevalence of carotid artery stenosis and plaque and identified their associated risk factors. Results revealed a standardized prevalence of 0.40% for carotid artery stenosis and 36.27% for carotid plaque. Notably, the highest rates of stenosis were observed in north and south China at 0.61%, while southwestern China exhibited the highest plaque prevalence at 43.17%. Key risk factors included older age, male gender, hypertension, diabetes, stroke, smoking, and atrial fibrillation. This study highlights significant geographical and demographic disparities in the prevalence of these conditions, underlining the urgent need for targeted interventions and policy reforms. These measures are essential for reducing the incidence of stroke and improving patient outcomes, addressing this significant health challenge in China.
Humans ; China/epidemiology* ; Male ; Female ; Prevalence ; Middle Aged ; Carotid Stenosis/epidemiology* ; Risk Factors ; Aged ; Adult ; Plaque, Atherosclerotic/epidemiology* ; Stroke/epidemiology* ; Aged, 80 and over

Objective To analyze the risk factors and build a clinical prediction model for hemodynamic depression (HD) after carotid artery stenting (CAS). Methods A total of 116 patients who received CAS in the Department of Vascular Surgery,Drum Tower Clinical College of Nanjing Medical University and the Department of Vascular Surgery,the Affiliated Suqian First People's Hospital of Nanjing Medical University from January 1,2016 to January 1,2022 were included in this study.The patients were assigned into a HD group and a non-HD group.The clinical baseline data and vascular disease characteristics of each group were collected,and multivariate Logistic regression was employed to identify the independent predictors of HD after CAS and build a clinical prediction model.The receiver operating characteristic (ROC) curve was drawn,and the area under the ROC curve (AUC) was calculated to evaluate the predictive performance of the model. Results The HD group had lower proportions of diabetes (P=0.014) and smoking (P=0.037) and higher proportions of hypertension (P=0.031),bilateral CAS (P=0.018),calcified plaque (P=0.001),eccentric plaque (P=0.003),and the distance<1 cm from the minimum lumen level to the carotid bifurcation (P=0.009) than the non-HD group.The age,sex,coronary heart disease,symptomatic carotid artery stenosis,degree of stenosis,and length of lesions had no statistically significant differences between the HD group and the non-HD group (all P>0.05).Based on the above predictive factors,a clinical prediction model was established,which showed the AUC of 0.807 and the 95% CI of 0.730-0.885 (P<0.001).The model demonstrated the sensitivity of 62.7% and the specificity of 87.7% when the best cut-off value of the model score reached 12.5 points. Conclusions Diabetes,smoking,calcified plaque,eccentric plaque,and the distance<1 cm from the minimum lumen level to the carotid bifurcation are independent predictors of HD after CAS.The clinical prediction model built based on the above factors has good performance in predicting the occurrence of HD after CAS.
Humans ; Carotid Stenosis ; Depression ; Models, Statistical ; Prognosis ; Stents ; Hemodynamics ; Plaque, Amyloid

BACKGROUND: There is still uncertainty regarding whether diabetes mellitus (DM) can adversely affect patients undergoing carotid endarterectomy (CEA) for carotid stenosis. The aim of the study was to assess the adverse impact of DM on patients with carotid stenosis treated by CEA. METHODS: Eligible studies published between 1 January 2000 and 30 March 2023 were selected from the PubMed, EMBASE, Web of Science, CENTRAL, and ClinicalTrials databases. The short-term and long-term outcomes of major adverse events (MAEs), death, stroke, the composite outcomes of death/stroke, and myocardial infarction (MI) were collected to calculate the pooled effect sizes (ESs), 95% confidence intervals (CIs), and prevalence of adverse outcomes. Subgroup analysis by asymptomatic/symptomatic carotid stenosis and insulin/noninsulin-dependent DM was performed. RESULTS: A total of 19 studies (n = 122,003) were included. Regarding the short-term outcomes, DM was associated with increased risks of MAEs (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 5.1%), death/stroke (ES = 1.61, 95% CI: [1.13-2.28], prevalence = 2.3%), stroke (ES = 1.55, 95% CI: [1.16-1.55], prevalence = 3.5%), death (ES = 1.70, 95% CI: [1.25-2.31], prevalence =1.2%), and MI (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 1.4%). DM was associated with increased risks of long-term MAEs (ES = 1.24, 95% CI: [1.04-1.49], prevalence = 12.2%). In the subgroup analysis, DM was associated with an increased risk of short-term MAEs, death/stroke, stroke, and MI in asymptomatic patients undergoing CEA and with only short-term MAEs in the symptomatic patients. Both insulin- and noninsulin-dependent DM patients had an increased risk of short-term and long-term MAEs, and insulin-dependent DM was also associated with the short-term risk of death/stroke, death, and MI. CONCLUSIONS In patients with carotid stenosis treated by CEA, DM is associated with short-term and long-term MAEs. DM may have a greater impact on adverse outcomes in asymptomatic patients after CEA. Insulin-dependent DM may have a more significant impact on post-CEA adverse outcomes than noninsulin-dependent DM. Whether DM management could reduce the risk of adverse outcomes after CEA requires further investigation.
Humans ; Endarterectomy, Carotid/adverse effects* ; Carotid Stenosis/surgery* ; Risk Factors ; Treatment Outcome ; Time Factors ; Stents/adverse effects* ; Diabetes Mellitus, Type 2/complications* ; Diabetes Mellitus, Type 1 ; Stroke/complications* ; Insulin/therapeutic use* ; Myocardial Infarction/complications* ; Risk Assessment

OBJECTIVE: To observe the clinical therapeutic effect of Tongdu Tiaoshen acupuncture combined with carotid endarterectomy (CEA) and simple CEA on carotid artery stenosis (CAS). METHODS: A total of 60 patients with CAS were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 3 cases dropped off). Both groups were treated with eversion CEA (eCEA). The conventional treatment of internal medicine and antiplatelet drugs i.e. aspirin enteric-coated tablet and clopidogrel hydrogen sulfate tablet were given in the control group for 4 weeks. On the basis of the treatment in the control group, Tongdu Tiaoshen acupuncture was applied at Baihui (GV 20), Fengfu (GV 16), Yamen (GV 15), cervical Jiaji (EX-B 2), Dazhui (GV 14), etc. in the observation group, once a day, 1-day rest was taken after 6-day treatment, 2 weeks were as one course and totally 2 courses were required. The carotid intima-media thickness (IMT) before and after treatment was detected by ultrasonic diagnostic apparatus, the TCM symptom score was compared before and after treatment and in the follow-up of 6 months after treatment, the clinical efficacy was evaluated in the two groups. The occurrence of endpoints within 1 year was recorded. RESULTS: After treatment, the carotid IMT and TCM symptom scores were decreased compared before treatment in the both groups (P<0.05), and the changes in the observation group were greater than the control group (P<0.05). In the follow-up, the TCM symptom scores were decreased compared before treatment in the both groups (P<0.05). The total effective rate was 96.4% (27/28) in the observation group, which was superior to 88.9% (24/27) in the control group (P<0.05). There were 1 case of stoke in the observation group and 2 cases of stroke in the control group within 1-year follow-up, and there was no significant difference in the number of endpoints between the two groups within 1 year (P>0.05). CONCLUSION Tongdu Tiaoshen acupuncture combined with CEA can effectively reduce the IMT in patients with CAS, improve the TCM symptom score, the efficacy is superior to simple CEA treatment.
Acupuncture Points ; Acupuncture Therapy ; Carotid Intima-Media Thickness ; Carotid Stenosis/therapy* ; Endarterectomy, Carotid ; Humans ; Treatment Outcome

The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.
Animals ; Brain Ischemia ; Carotid Stenosis/drug therapy* ; Cognitive Dysfunction/etiology* ; Digoxin ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; White Matter

Objective: To investigate the correlation between cerebral small vessel disease (CSVD) and carotid low-density plaque on multi-slice spiral CT angiography (MSCTA) in patient with carotid stenosis. Methods: The clinical data of 221 patients with carotid stenosis who admitted to Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, from January 2016 to January 2021 were retrospectively analyzed. There were 195 males and 26 females, with the age of (70.0±8.4) years (range: 48 to 88 years). According to MRI, the patients were divided into carotid stenosis combined with CSVD group (the CSVD group) and carotid stenosis without CSVD group (the non-CSVD group). Lowest density in the carotid atherosclerotic plaque area (CAPALD) was analyzed by MSCTA. The t-test, Mann-Whitney U test and Chi-square test were used for comparison between the two groups. Univariate and multivariate Logistic regression analysis were performed on CAPALD and other clinical indicators with CSVD. Receiver operating characteristic (ROC) curves of CAPALD and CAPALD combined with the demographics (sex, age and body mass index) were plotted for predicting CSVD, and the area under the curve (AUC), sensitivity and specificity were calculated. Results: There were 169 patients in the CSVD group and 52 patients in the non-CSVD group. In the CSVD group, 88.8% (150/169) were males and 11.2% (19/169) were females, with the age of (70.5±8.2) years (range: 48 to 88 years). In the non-CSVD group, 86.5% (45/52) were males and 13.5% (7/52) were females, with the age of (68.4±9.1) years (range: 51 to 85 years). CAPALD and the score of Montreal cognitive assessment were lower in the CSVD group than those in the non-CSVD group (21.0 HU vs. 35.0 HU, Z=-3.760, P<0.01; 22.6±3.9 vs. 24.8±3.3, t=-2.064, P<0.05). Multivariate Logistic regression analysis showed that CAPALD was an independent factor for CSVD (OR=1.044, 95%CI:1.020 to 1.070, P<0.01). The AUC of the ROC curve for CAPALD predicting carotid stenosis with CSVD was 0.672 (P<0.01), with cut-off value of 34.5 HU, sensitivity of 82.8%, and specificity of 50.0%. The AUC of ROC curve for CAPALD combined with the demographics predicting CSVD was 0.733 (P<0.01), with sensitivity of 82.9% and specificity of 64.0%. Conclusions: The decreased CAPALD is a risk factor for CSVD in patients with carotid stenosis. The analysis of carotid plaque density by MSCTA may help to identify the patients at high risk of CSVD.
Aged ; Aged, 80 and over ; Humans ; Middle Aged ; Carotid Stenosis ; Cerebral Small Vessel Diseases ; Retrospective Studies

OBJECTIVE: To analyze the feasibility of using vascular plaque quantification (VPQ) to evaluate carotid atherosclerotic plaques and to observe the effect of statins on carotid atherosclerotic plaques. METHODS: Patients with carotid plaques from January 2016 to September 2018 in Peking University First Hospital Neurology Department were recruited and underwent three-dimonsional ultrasound (3DUS). Their gray scale median (GSM) and other parameters of carotid plaques were measured with VPQ. The patients were divided into low GSM group (GSM < 40) and high GSM group (GSM≥40). The clinical characteristics and plaque characteristics of the patients in the two groups were compared to analyze the stability of plaques. According to whether taking statins or not, the patients were further divided into statin group and non-statin group, plaque GSM and other parameters of their carotid plaques were measured and the changes of carotid plaques at the end of 3 months and 2 years were observed. RESULTS: A total of 120 patients were enrolled, including 79 males and 41 females, with an average age of (65.39±9.11) years. The patients were divided into low GSM group (31 cases) (GSM < 40) and high GSM group (89 cases) (GSM≥40). The stenosis of the lumen in the low GSM group was more severe (the area stenosis rate was 41.32%±21.37% vs. 29.79%±17.16%, P < 0.05). The nor-malized wall index (NWI) of plaque in low GSM group was significantly higher than that in high GSM group (0.61 ±0.14 vs. 0.52±0.12, P < 0.01). A total of 77 patients, including 51 males and 26 females, aged (64.96±9.58) years, were enrolled to observe the statin effects on carotid plaque. They were divided into statin group (n=56) and non-statin group (n=21) according to whether taking statins or not. At the baseline and 3-month follow-up, there were no significant differences in carotid plaque volume, area, degree of luminal stenosis and GSM between the two groups (P>0.05). At the end of the 2-year follow-up, GSM increased in the statin group [median 10.00 (2.00, 28.00)] but decreased in the non-statin group [median －7.00 (－11.00, 5.50)], with a statistically significant difference between the two groups (P < 0.01). There was no significant increase in carotid plaque volume in the statin group, while there was a slight increase in the non-statin group, but there was no significant difference between the two groups [median increase in plaque volume was 0.00 (－30.00, 40.00) mm³ in the statin group and 30.00 (10.00, 70.00) mm³ in the non-statin group, P>0.05]. CONCLUSION The VPQ technology of 3DUS can be used to evaluate carotid atherosclerotic plaques. Patients with low GSM (GSM < 40) have more severe vascular stenosis and higher normalized wall index. VPQ technology can also be used to observe the effect of statins on carotid plaque, the GSM of plaques increase in patients who are taking moderate-intensity statin treatment for two years.
Aged ; Carotid Stenosis/diagnostic imaging* ; Constriction, Pathologic ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Male ; Middle Aged ; Plaque, Atherosclerotic/drug therapy* ; Technology ; Ultrasonography

Carotid Artery, Internal/surgery* ; Carotid Stenosis/surgery* ; Endarterectomy, Carotid ; Humans ; Treatment Outcome

To investigate cerebral autoregulation(CA)in patients with severe unilateral carotid artery stenosis by near infrared spectroscopy. Thirty patients who underwent general anesthesia in our hospital from January 2015 to February 2017 were enrolled in this study.The stenosis group included 15 patients with severe unilateral internal carotid artery stenosis,and the control group included 15 patients without carotid artery stenosis.Both groups were matched in sex and age.Cerebral tissue oxygenation index(TOI)and mean arterial pressure were recorded continuously under stable general anesthesia.The Pearson correlation coefficient()was calculated to judge the CA status. TOI was not significantly different between the stenosis side and the non-stenosis side in the stenosis group(66.52±6.50 65.23±4.50;=0.93, =0.368)or between the stenosis side in the stenosis group and the stenosis side in the control group(66.52±6.50 64.22±3.87;=1.18, =0.248).The values of stenosis side and non-stenosis side in the stenosis group were 0.36±0.12 and 0.17±0.11,respectively,and the values of the stenosis side in the stenosis group and the stenosis side of the control group were 0.36±0.12 and 0.13±0.08,respectively.In the stenosis group,5 patients had transient ischemic attack and 2 patients had a history of stroke within 3 months before operation.When an value of 0.342 was used as the judgment point of CA abnormality,the sensitivity and specificity were 0.625 and 0.909,respectively. Within the range of normal blood pressure fluctuation,cerebral blood flow is linked to blood pressure at the stenosis side in patients with severe unilateral carotid artery stenosis.
Blood Pressure ; Carotid Stenosis ; Cerebrovascular Circulation ; Homeostasis ; Humans ; Ischemic Attack, Transient