Table of Content

20 October 2024, Volume 19 Issue 10

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Advances in Pharmacogenomics-Based Individualized Antithrombotic Therapy for Acute Ischemic Stroke

YANG Jiajie, ZHANG Liang, HUANG Li’an

2024, 19(10):  1111-1117.  DOI: 10.3969/j.issn.1673-5765.2024.10.001

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Antithrombotic therapy is a key measure for preventing acute ischemic stroke recurrence. With the advancement of multi-omics research and the identification of more genes affecting drug safety and efficacy, pharmacogenomics is gaining attention for its role in individualized therapy. This paper reviews the progress of research on pharmacogenomics in guiding antithrombotic therapy for patients with acute ischemic stroke, aiming to elucidate the potential of gene detection in optimizing drug selection and dosage adjustments. Studies have shown that the efficacy of drugs like clopidogrel is modulated by polymorphisms in the cytochrome P450 family 2 subfamily C member 19 (CYP2C19) gene. Patients carrying loss-of-function alleles such as CYP2C19*2 or CYP2C19*3 demonstrate diminished responses to standard antiplatelet therapy and cannot effectively reduce the risk of stroke recurrence. However, gene detection can significantly improve treatment outcomes by guiding drug selection. Additionally, for patients with cardioembolic stroke, warfarin or novel oral anticoagulants are commonly used as primary antithrombotic treatment options. The dosage effects of warfarin are closely related to the polymorphisms in genes such as cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1). Gene detection can help physicians individualize warfarin dosing, reducing the occurrence of bleeding or thrombotic events. In conclusion, the application of pharmacogenomics in antithrombotic therapy for acute ischemic stroke provides a new idea for individualized therapy, with the potential to further improve the safety and efficacy in the future.

Dual Antiplatelet Therapy in Patients with Special Ischemic Stroke

HUANG Li’an

2024, 19(10):  1118. 

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Study on the Clinical Efficacy of Antiplatelet Therapy Guided by CYP2C19 Gene Detection in Ischemic Stroke Patients of Different Ethnic Groups

XIE Yaoyi, HUANG Yanju, FAN Min, CEN Huatao, LI Yanli, LU Miaozhi, LU Boan, WEI Rangfang, WU Zhiwu

2024, 19(10):  1119-1124.  DOI: 10.3969/j.issn.1673-5765.2024.10.002

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Objective  To analyze the difference in response of antiplatelet therapy guided by cytochrome P450 family 2 subfamily C member 19 (CYP2C19) gene detection in ischemic stroke patients of different ethnic groups.
Methods  The prospective study consecutively included Han (the control group) and Zhuang (the experimental group) patients with non-cardiogenic mild ischemic stroke who were hospitalized for treatment at the Third People’s Hospital of Nanning from January to July 2023. All patients were administered antiplatelet therapy, with the choice of medication guided by CYP2C19 gene detection results. Fast metabolizers were given clopidogrel bisulfate, while intermediate or slow metabolizers were given enteric-coated aspirin or ticagrelor. A follow-up period of 90 days was established to record the mRS scores, activity of daily living scale (ADL) scores, NIHSS scores, and the cumulative recurrence rates of ischemic stroke at 90 days.
Results  A total of 1036 patients with ischemic stroke were included, with 743 in the control group. The results of the CYP2C19 gene detection showed that there were 299 (40.24%) fast metabolizers, 
345 (46.43%) intermediate metabolizers, and 99 (13.32%) slow metabolizers of clopidogrel. In the experimental group, there were 293 patients, with 107 (36.52%) fast metabolizers, 161 (54.95%) intermediate metabolizers, and 25 (8.53%) slow metabolizers of clopidogrel. The differences in the proportion of different CYP2C19 genotypes between the two groups were not statistically significant. After a 90 days follow-up, there was no significant difference in mRS scores, ADL scores, and NIHSS scores between the two groups. The cumulative recurrence rates of ischemic stroke at 90 days for the control group and the experimental group were 5.52% (41/743) and 5.12% (15/293), respectively, with no statistically significant difference.
Conclusions  Antiplatelet therapy guided by CYP2C19 gene detection has similar effects in preventing the recurrence of ischemic stroke in Han and Zhuang patients.




A Case Report of Dual Antiplatelet Therapy for Acute Basilar Artery Occlusion Based on Rapid CYP2C19 Gene Detection

HOU Yuting, LI Tong

2024, 19(10):  1125-1130.  DOI: 10.3969/j.issn.1673-5765.2024.10.003

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This article described a case of a patient with antiplatelet therapy after interventional therapy for posterior circulation ischemia based on gene detection. The patient was an elderly female with acute ischemic stroke caused by middle segment occlusion of the basilar artery. She was admitted within 3 hours of onset and received intravenous thrombolysis followed by bridging interventional therapy. After treatment, the patient recovered well (NIHSS score decreased from 11 points at admission to 2 points at discharge). In order to individualize the selection of the patient’s antiplatelet therapy regimen, cytochrome P450 family 2 subfamily C member 19 (CYP2C19) gene detection was performed after interventional therapy, which showed an intermediate metabolism type, indicating that the patient may have clopidogrel resistance. Therefore, the dual antiplatelet therapy regimen of ticagrelor combined with aspirin was selected for 3 months for antiplatelet therapy, and then the medication was adjusted according to the patient’s follow-up. At two months of follow-up after discharge, the prognosis was good and there were no bleeding manifestations.



A Case Report of Dual Antiplatelet Therapy for Severe Stenosis of the Internal Carotid Artery Based on Rapid CYP2C19 Gene Detection

ZHANG Taihui, REN Hong

2024, 19(10):  1131-1134.  DOI: 10.3969/j.issn.1673-5765.2024.10.004

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This paper reported the clinical diagnosis and treatment process of an elderly female patient with in-hospital stroke. The patient suddenly developed acute ischemic stroke 2 days after an anorectal surgery and was diagnosed with severe stenosis at the origin of the right internal carotid artery by imaging examination. After one month of treatment with secondary prevention drugs for stroke, selective endovascular treatment was performed. The rapid detection of cytochrome P450 family 2 subfamily C member 19 (CYP2C19) gene before the operation showed that it was an intermediate metabolic type, suggesting that the effect of clopidogrel may be poor. Based on this result, the antiplatelet therapy regimen was adjusted and ticagrelor combined with aspirin was selected as a replacement therapy. After treatment, the patient’s condition was stable and the prognosis was good. This report suggests that rapid detection of the CYP2C19 gene can also be used to guide the selection of antiplatelet therapy strategies and improve outcomes in non-mild stroke patients.



Analysis of Influencing Factors of Cognitive Impairment in Patients with Cerebral Small Vessel Disease and Construction and Validation of a Nomogram Model

DAI Jie, ZHANG Suxiang, ZHAO Shasha, ZHANG Xiaofeng

2024, 19(10):  1136-1142.  DOI: 10.3969/j.issn.1673-5765.2024.10.005

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Objective  To analyze the factors influencing cognitive impairment in patients with cerebral small vessel disease.
Methods  Patients with cerebral small vessel disease admitted to Cangzhou Central Hospital from January 2020 to May 2022 were retrospectively selected (systematic sampling) as the modeling group, and divided into the non-cognitive impairment group and the cognitive impairment group according to the occurrence of cognitive impairment. Multivariate logistic regression model was used to analyze the influencing factors of cognitive impairment in patients with cerebral small vessel disease. A nomogram model was constructed in R3.6.3 to predict cognitive impairment in cerebral small vessel disease. In addition, patients with cerebral small vessel disease admitted from May 2022 to May 2023 were collected as the validation group. The radio of the modeling group to the validation group is 7∶3. This validation group was used for external validation of the constructed model. The ROC curve was developed to evaluate the discrimination of the nomogram model in assessing cognitive impairment in cerebral small vessel disease.  
Results  A total of 247 patients were included in this study, including 173 in the modeling group and 74 in the validation group. In the modeling group, 61 cases (35.26%) had cognitive impairment, while in the validation group, 24 cases (32.43%) had cognitive impairment. Multivariate analysis showed that high levels of CRP (OR 1.527, 95%CI 1.271-1.834, P＜0.001), hypertension (OR 2.106, 95%CI 1.044-4.248, P=0.037), carotid atherosclerosis (OR 3.917, 95%CI 1.416-10.833, P=0.009), hyperhomocysteinemia (OR 3.220, 95%CI 1.261-8.226, P=0.015), and the degree of white matter lesion (OR 2.862, 95%CI 1.496-5.475, P=0.001) were the risk factors for cognitive impairment in patients with cerebral small vessel disease. The AUC of ROC was 0.834 (95%CI 0.791-0.902, P<0.001), indicating that the discrimination of the nomogram model was good. The calibration curve slope was approximately 1 (χ²=4.388, P=0.820), indicating that the fitting degree of the nomogram model was good. External validation results showed that the AUC of ROC was 0.845 (95%CI 0.802-0.911, P<0.001), the slope of calibration curve was close to 1, and the fitting degree was good (χ²=6.042, P=0.302).
Conclusions  CRP, hypertension, carotid atherosclerosis, hyperhomocysteinemia, and the degree of white matter lesion may all lead to cognitive impairment in patients with cerebral small vessel disease. The nomogram model constructed with these indicators to predict the risk of cognitive impairment in patients with cerebral small vessel disease has good discrimination and consistency.


Effects of Probucol Combined with Atorvastatin Calcium in the Treatment of Acute Cerebral Infarction

HUANG Yanling, YANG Liu, YUAN Dezhi, WANG Xuefei, WANG Hui, MENG Tao

2024, 19(10):  1143-1147.  DOI: 10.3969/j.issn.1673-5765.2024.10.006

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Objective  To evaluate the effects of probucol combined with atorvastatin calcium in the treatment of acute cerebral infarction (ACI), with the aim of providing a therapeutic reference for ACI. 
Methods  Data of ACI patients hospitalized within 24 h of symptom onset at Chongqing Emergency Medical Center from January 2018 to September 2023 were retrospectively collected. Patients included in the study met specific criteria, which included receiving lipid-regulating therapy with atorvastatin calcium (20 mg, qn) monotherapy or combined with probucol (0.5 mg, bid) for a treatment duration exceeding 3 months. Patients were divided into the combined treatment group and the control group according to whether probucol was combined or not. The study compared differences in neurological function (measured by the NIHSS), neurological outcome (measured by the mRS), life ability [measured by the Barthel index], and lipid levels (including TC, TG, HDL-C and LDL-C) between the two groups. 
Results  A total of 102 patients were enrolled in the study, including 56 in the combined treatment group and 46 in the control group. There was no statistically significant difference in baseline data between the two groups. The NIHSS scores and lipid levels in both groups at 14 days post-treatment, as well as the lipid levels after 3 months of treatment, showed significant improvement compared to baseline controls (P<0.001). After 14 days of treatment, the NIHSS score (P=0.031), TC (P=0.005) and LDL-C (P=0.044) levels of the combined treatment group were lower than those of the control group, while the Barthel index score (P=0.004) was higher than that of the control group. The difference was statistically significant. After 3 months of treatment, the mRS score (P<0.001), TC (P<0.001), TG (P=0.002) and LDL-C (P<0.001) levels of the combined treatment group were lower than those of the control group, while the Barthel index score (P<0.001) was higher than that of the control group. The difference was statistically significant. The recurrence rate of cerebral infarction during the 3 months follow-up period was 0 in the combined treatment group and 2.17% in the control group. The difference was not statistically significant (P= 0.268).
Conclusions  The combination of probucol and atorvastatin calcium in treating patients in the acute phase of ACI demonstrated superior clinical efficacy compared to atorvastatin calcium alone. This combination effectively reduced lipid levels and improved neurological function and ability to live.


Effects of Different Oxygen Supply Methods during Hyperbaric Oxygen Therapy on the Transcutaneous Oximetry of Post-Surgery Stroke Patients

REN Ziqi, WANG Qinfang, LIU Yaling, WANG Cong, YU Qiuhong

2024, 19(10):  1148-1154.  DOI: 10.3969/j.issn.1673-5765.2024.10.007

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Objective  To evaluate the changes in transcutaneous oximetry (TcPO₂) within 30 days of stroke onset in post-surgery patients under hyperbaric oxygen therapy with different oxygen supply methods.
Methods  Post-surgery stroke patients who received treatment in the hyperbaric oxygen department within 30 days of onset from January 1, 2023 to June 20, 2024 were included in this retrospective analysis. According to the airway condition, normal airway patients were supplied with a mask and reservoir bag (the mask group) and artificial airway patients with ventilator weaning were supplied with a head hood (the head hood group). The TcPO₂ was monitored in real time during hyperbaric oxygen therapy and compared the changes of TcPO₂ between the two oxygen supply methods. 
Results  A total of 26 patients were included in this study, including 13 patients in the mask group and 13 patients in the head hood group. In the mask group, TcPO₂ was (55.92±9.58) mmHg (1 mmHg=0.133 kPa) before compression, and the mean and maximum TcPO₂ during oxygen inhalation stage were (679.30±186.80) mmHg and (881.40±208.20) mmHg, respectively. After decompression, TcPO₂ was (83.71±21.54) mmHg. In the head hood group, TcPO₂ was (62.92±14.84) mmHg before compression, the mean and maximum TcPO₂ during oxygen inhalation stage were (369.50±163.00) mmHg and (487.90±212.10) mmHg, respectively. After decompression, TcPO₂ was (84.25±19.95) mmHg. The mean and maximum of TcPO₂ during oxygen inhalation stage in the mask group were higher than those in the head hood group, and the differences were statistically significant (P<0.01). The TcPO₂ of the mask group and the head hood group began to increase after oxygen inhalation for 10 minutes. In the mask group, TcPO₂ reached the saturation at 30 minutes, while in the hood group, TcPO₂ increased dynamically with the extension of oxygen inhalation time until the end of oxygen inhalation.
Conclusions  During hyperbaric oxygen therapy, both mask oxygen supply and head hood oxygen supply increased the TcPO₂ level of post-surgery stroke patients, and the oxygen inhalation effect of mask should be better than that of head hood.




Study on the Value of YKL-40 and Caspase-1 Levels and ASPECTS in Predicting the Prognosis of Patients with Anterior Circulation Massive Cerebral Infarction after Interventional Thrombectomy

WANG Jiwei, LI Hui, LIU Jianfeng, XU Lifeng, BI Hongling, XIE Xiongwei, TIAN Yangyang

2024, 19(10):  1155-1161.  DOI: 10.3969/j.issn.1673-5765.2024.10.008

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Objective  To investigate the effects of chitinase protein-40 (YKL-40) and cysteine proteolytic enzyme-1 (Caspase-1) levels and ASPECTS on the prognosis of patients with anterior circulation massive cerebral infarction (MCI) after interventional thrombectomy.
Methods  Data of 180 patients with anterior circulation MCI who received interventional thrombectomy in The First Hospital of Hebei Medical University from June 2020 to February 2023 were retrospectively analyzed. The patients were divided into the death group (41 cases) and the survival group (139 cases) according to the prognosis 3 months after interventional thrombectomy. Baseline data and YKL-40 and Caspase-1 levels before interventional thrombectomy were compared between the two groups. Cox regression analysis was used to explore the prognostic factors of interventional thrombectomy for MCI. ROC curve analysis was used to assess the efficacy of YKL-40 and Caspase-1 levels and ASPECTS in predicting the prognosis of patients with MCI after interventional thrombectomy. 
Results  The age and infarct area of the death group were higher than those of the survival group, while the ASPECTS were lower (all P＜0.001). Serum YKL-40 level [(141.37±12.40) μg/L vs. (115.05±11.40) μg/L] and Caspase-1 level [(13.05±1.15) ng/L vs. (8.61±0.64) ng/L] in the death group were higher than those in the survival group (all P＜0.001). Cox regression analysis showed that large infarct area (HR 1.011, 95%CI 1.001-1.022), high YKL-40 level (HR 1.033, 95%CI 1.001-1.066), and high Caspase-1 level (HR 1.576, 95%CI 1.264-1.966) were independent risk factors for death after interventional thrombectomy of anterior circulation MCI, while the high ASPECTS (HR 0.887, 95%CI 0.794-0.991) was the protective factor for death after interventional thrombectomy of anterior circulation MCI. ROC curve analysis results showed that the combined prediction of serum YKL-40 and Caspase-1 levels and ASPECTS yielded a better predictive accuracy (AUC 
0.940, 95%CI 0.890-0.990) than any of these three indexes alone in predicting death after interventional thrombectomy of anterior circulation MCI [the AUC was 0.869 (95%CI 0.806-0.933), 0.897 (95%CI 0.828-0.966), and 0.724 (95%CI 0.642-0.806), respectively].
Conclusions  YKL-40 and Caspase-1 levels and ASPECTS were closely related to the prognosis of patients with anterior circulation MCI after interventional thrombectomy. Consequently, these indexes could be used as prognostic indicators.


Relationship between Serum MicroRNA-874-3p, MicroRNA-181a-5p, Wnt/β-catenin Signaling Pathway and Neurological Function Prognosis in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis

CHEN Xubin, XIAO Weiting, YUE Xifeng, HE Nengqing, ZENG Xiaohui

2024, 19(10):  1162-1169.  DOI: 10.3969/j.issn.1673-5765.2024.10.009

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Objective  To investigate the relationship between serum microRNA-874-3p (miR-874-3p), 
microRNA-181a-5p (miR-181a-5p), Wnt/β-catenin signaling pathway and neurological function prognosis in patients with acute ischemic stroke (AIS). 
Methods  AIS patients who received intravenous thrombolytic therapy in Shenzhen Longhua District Central Hospital from March 2021 to December 2022 were prospectively included into the AIS group, and healthy subjects during the same period were selected into the control group. The relative expression levels of serum miR-874-3p, miR-181a-5p and peripheral blood mononuclear cell (PBMC) determination of Wnt/β-catenin were detected and compared between the two groups. Pearson correlation was used to analyze the correlation between the expression of miR-874-3p and miR-181a-5p in serum and the Wnt/β-catenin signaling pathway in AIS patients. All AIS patients were followed up for 3 months after discharge. Patients who completed follow-up were divided into the good neurological function prognosis group and the poor neurological function prognosis group based on the mRS score. The relative expression levels of miR-874-3p and miR-181a-5p were compared between the two groups. Multivariate logistic regression equation was used to analyze the factors affecting the prognosis of neurological function in AIS patients. 
Results  In this study, 185 patients were included in the AIS group, with an average age of (62.8±7.3) years. The control group included 65 healthy subjects with an average age of (63.4±6.9) years. Compared with the control group, the relative expression levels of miR-874-3p in serum (1.02±0.21 vs. 1.46±0.23, P<0.001) and Wnt mRNA (2.41±0.64 vs. 4.59±1.13, P<0.001), β-catenin mRNA in PBMC (1.19±0.18 vs. 2.34±0.73, P<0.001) in the AIS group were lower than those in the control group. The relative expression level of miR-181a-5p (1.95±0.32 vs. 1.27±0.27, P<0.001) was higher than that of the control group. Pearson correlation analysis showed that the expression of serum miR-874-3p was positively correlated with the expression of Wnt mRNA (r=0.562, P<0.001) and β-catenin mRNA (r=0.611, P<0.001) in PBMC, while the expression of miR-181a-5p was negatively correlated with the expression of Wnt mRNA (r=-0.586, P<0.001) and β-catenin mRNA (r=-0.595, P<0.001) in PBMC in AIS patients. In the AIS group, there were 104 patients with good neurological function prognosis and 81 patients with poor neurological function prognosis. The rate of poor neurological function prognosis was 43.78%. The relative expression level of miR-874-3p in serum in the poor neurological function prognosis group was significantly lower than that in the good neurological function prognosis group (0.79±0.20 vs. 1.20±0.22, P<0.001). The relative expression level of miR-181a-5p was significantly higher than that of the good neurological function prognosis group (2.26±0.31 vs. 1.71±0.24, P<0.001). In the poor neurological function prognosis group, age [(65.48±7.45) years vs. (62.29±7.21) years, P=0.004], time from onset to admission[(4.36±1.03) h vs. (3.79±1.15) h, P=0.001], the NIHSS score [(6.81±2.45) points vs. (4.67±1.76) points, P<0.001] and serum Hcy levels [(13.34±4.12) μmol/L vs. (11.75±3.46) μmol/L, P=0.005] were significantly higher than those in the good neurological  function prognosis group. Multivariate logistic regression results showed that older age (OR 1.056, 95%CI 1.005-1.108, P=0.029), extend time from onset to admission (OR 1.125, 95%CI 1.008-1.256, P=0.035), high NIHSS score (OR 1.220, 95%CI 1.093-1.362, P<0.001), low expression of miR-874-3p (OR 0.632, 95%CI 0.498-0.803, P<0.001), and high expression of miR-181a-5p (OR 1.506, 95%CI 1.209-1.875, P<0.001) were risk factors for poor prognosis of AIS neurological function. 
Conclusions  The expression of serum miR-874-3p decreased and miR-181a-5p increased in AIS patients, both of which were related to the Wnt/β-catenin signaling pathway. The levels of serum miR-874-3p and miR-181a-5p were influencing factors for the prognosis of neurological function in patients.


Study on the Brain Protection of Granulocyte Colony-Stimulating Factor in Stroke after Alcohol Use Disorder

HAO Dandan, WANG Danyang, LI Li

2024, 19(10):  1170-1179.  DOI: 10.3969/j.issn.1673-5765.2024.10.010

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Objective  To examine the effects of granulocyte colony-stimulating factor (G-CSF) treatment on the expression of transforming growth factor-α (TGF-α) in microglia and its neuroprotective effects in stroke after alcohol use disorder (AUD) in rats. 
Methods  Male Sprague-Dawley rats were used to establish an AUD model using the double bottle method. Based on the AUD model, the focal cerebral ischemia model of middle cerebral artery occlusion (MCAO) was established using the thread embolism method. TGF-α small interfering RNA (siRNA) or negative control siRNA was injected into the lateral ventricle 
24 h before MCAO. G-CSF was injected intraperitoneally l h after ischemia-reperfusion injury. Rats were randomly divided into the AUD group (18 rats), the AUD+MCAO group (18 rats), the AUD+MCAO+G-CSF group (18 rats), the AUD+MCAO+G-CSF+TGF-α siRNA group (18 rats), and the AUD+MCAO+G-CSF+control siRNA group (6 rats). Alcohol intake, changes in alcohol preference, and neurological function scores of the rats were recorded. The volume of cerebral infarction 24 h after MCAO was measured by 2,3,5-triphenyltetrazolium chloride staining. The number of positive cells of transmembrane protein 119 (TMEM119), a specific marker of microglia in the cerebral cortex of the ischemic side, and the G-CSF receptor (G-CSFR), and the protein expression of TGF-α were observed by immunofluorescence staining. The expression levels of TMEM119 and TGF-α protein in brain tissue of the ischemic side were detected by Western blot.
Results  Alcohol intake and alcohol preference of rats gradually increased with the increase of drinking time. G-CSFR was significantly expressed in microglia. Compared with the AUD group, the fluorescence intensity of TMEM119 protein and TGF-α protein in the AUD+MCAO group was significantly enhanced, and the number of positive cells increased. Compared with the AUD+MCAO group, the volume of infarction in the AUD+MCAO+G-CSF group was significantly reduced, and the symptoms of neurological impairment improved. The fluorescence intensity of TMEM119 protein was significantly weakened, and the number of positive cells decreased. The fluorescence intensity of TGF-α protein was significantly enhanced, and the number of positive cells increased. Volume of cerebral infarction increased and neurological deficits aggravated in the rats after lateral ventricle injection of TGF-α siRNA. 
Conclusions  G-CSF plays an important brain protective effect in stroke after AUD by increasing the expression of TGF-α in microglia.




Effects of Penehyclidine Hydrochloride on the Blood-Brain Barrier and ROCK2, CLDN5, and AQP-4 Expression of Brain Tissue in Rats with Intracerebral Hemorrhage

LI Dayu, GUO Shaolei, ZHANG Bo, HUANG Zhipeng, YE Weiwei, YAO Liang

2024, 19(10):  1180-1187.  DOI: 10.3969/j.issn.1673-5765.2024.10.011

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Objective  To explore the effects of penehyclidine hydrochloride (PHC) on the blood-brain barrier (BBB) and the expression of Rho associated coiled-coil containing protein kinase 2 (ROCK2), claudin 5 (CLDN5), and aquaporin-4 (AQP-4) in rats with intracerebral hemorrhage (ICH). 
Methods  A total of 100 SD rats were divided into 20 rats/group as the sham group, the ICH group, the PHC-L group (1 mg/kg PHC), the PHC-M group (2 mg/kg PHC), and the PHC-H group (4 mg/kg PHC). The rat model of ICH was established by autologous blood (50 μL) injection method (except for the sham group). After successful modeling, the rats in the PHC-L, PHC-M, and PHC-H groups were intraperitoneally injected with the corresponding doses of PHC. The sham group and the ICH group were injected with an equal amount of 0.9% sodium chloride solution for 7 consecutive days, once a day. The Longa scoring method was used to score the neurological impairment in rats. A transmission electron microscope was used to observe the ultrastructure of BBB. The Evans blue (EB) method was used to evaluate the permeability of BBB and the water content in rat brain tissue was detected. Immunohistochemical staining and western blot were used to detect the expressions of ROCK2, CLDN5, and AQP-4 in brain tissue. 
Results  Compared with the sham group, the neurological impairment score [0 score vs. (2.45±0.48) score], EB content [(9.75±1.01) μg/g vs. (32.07±3.22) μg/g], brain tissue water content [(77.21±0.33) % vs. (80.96±0.45) %], ROCK2 integrated optical density (IOD) [(1.02±0.14)×103 vs.(11.05±0.71)×103] and relative expression (0.39±0.03 vs. 1.43±0.24), AQP-4 IOD [(1.67±0.18)×103 vs. (10.85±0.58)×103] and relative expression (0.60±0.07 vs. 1.69±0.21) increased significantly in the ICH group, while the CLDN5 IOD [(10.83±0.64)×103 vs. (3.02±0.33)×103] and relative expression (1.53±0.20 vs. 0.42±0.06) decreased significantly. Compared with the ICH group, the PHC-L, PHC-M, and PHC-H groups reversed the trend of changes in the aforementioned indicators to varying degrees according to different doses of PHC.  
Conclusions  PHC can ameliorate structural damage to the BBB in ICH rats, potentially through up-regulating the level of CLDN5 and inhibiting the expression of ROCK2 and AQP-4.


Consensus of Experts on the Application of Cardiac Magnetic Resonance in Patients with Ischemic Stroke

Medical Imaging Society of Chinese Stroke Association, Society of Magnetic Resonance, Chinese Research Hospital Association, Yunnan Stroke Association

2024, 19(10):  1188-1196.  DOI: 10.3969/j.issn.1673-5765.2024.10.012

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Stroke is the leading cause of death and disability in Chinese residents, with ischemic stroke (IS) accounting for approximately 70% of stroke patients. In IS, cardioembolic stroke and embolic stroke of undetermined source account for 20%-30% and 30%-40%, respectively. Cardiac magnetic resonance (CMR) examination is an important adjunctive diagnostic tool, facilitating the identification of IS etiology while also revealing the novel pathogenesis. This article discussed the necessity of CMR examination in IS patients, the value of CMR examination techniques, and the indications for its application in IS patients. It also recommended the procedure of CMR examination for IS patients to provide better help for the diagnosis, treatment, and secondary prevention of IS.



Sleep Disorders and Stroke Rehabilitation: Exploration of Treatment Strategies from the Neuroplasticity Perspective

WU Xiaoli, LIU Lixu

2024, 19(10):  1197-1204.  DOI: 10.3969/j.issn.1673-5765.2024.10.013

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Stroke, as a neurological disease characterized by high disability and mortality rates, poses a significant threat to the long-term quality of life for patients. Effective neurofunctional rehabilitation measures can substantially mitigate the long-term disabilities induced by stroke. Motor relearning, a crucial mechanism in post-stroke rehabilitation, is heavily reliant on good sleep quality. However, stroke patients often suffer from sleep disorders, which have a non-negligible negative impact on rehabilitation outcomes. This paper delved into the bidirectional relationship and pathophysiological mechanisms between sleep disorders and stroke rehabilitation. It also reviewed the application and prospect of emerging technologies such as non-invasive/invasive brain stimulation, virtual reality therapy, wearable sleep tracking devices, and gene therapy in stroke patients with sleep disorders, aiming to provide new perspectives and effective methods for optimizing stroke rehabilitation strategies, so as to enhance the rehabilitation effects and quality of life for stroke patients.

Research Progress on the Correlation between Neuroinflammation and Brain Iron Metabolism after Intracerebral Hemorrhage

JU Jiajun, WANG Xinxin, HANG Lihua

2024, 19(10):  1205-1214.  DOI: 10.3969/j.issn.1673-5765.2024.10.014

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Intracerebral hemorrhage refers to bleeding caused by non-traumatic rupturing of blood vessels within the brain, which is a serious neurological disorder. Its main pathophysiological characteristics include massive bleeding and neuron death, which impair the neuroimmune system and severely affect the patient’s prognosis. Iron ion homeostasis is crucial for maintaining normal neurological function. However, following intracerebral hemorrhage, disrupted iron metabolism leads to iron accumulation in the brain. Excessive iron participates in neuroinflammatory responses by activating inflammatory signaling pathways and regulating the function of inflammatory cells, while neuroinflammatory cells also participate in regulating the transportation and storage of iron ions. The interaction between the two exacerbates neurol damage. This article reviews the progress of research on the correlation between neuroinflammation and brain iron metabolism after intracerebral hemorrhage, aiming to provide a reference for the clinical treatment of intracerebral hemorrhage.



Progress in the study of Dopamine Receptor Agonists for Brain Protection after Ischemic Brain Injury

ZHANG Linyao, LIU Lixu

2024, 19(10):  1215-1220.  DOI: 10.3969/j.issn.1673-5765.2024.10.015

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Ischemic brain injury comprises 87% of all brain injuries and typically results in severe functional impairments. Dopamine, the most abundant catecholamine neurotransmitter in the brain, is intimately linked with autonomous movement, emotion, sleep, cognition, and other critical functions. Following ischemic brain injury, patients have severe dysfunction of dopamine in the brain. Studies have demonstrated that dopamine receptor agonists, such as ropinirole, pramipexole, and piribedil, can mitigate brain injury through both receptor-dependent and non-receptor-dependent pathways. These agonists have significant improvements in functions including learning, memory, behavior, and consciousness. This article reviews the potential mechanisms of various dopamine receptor agonists in brain protection after ischemic brain injury.

Construction Specification of Directed Acyclic Graphs: An Introduction to the ESC-DAGs Method and Case Interpretation in Cerebrovascular Disease Research

HAO Yunyi, XIA Xue, XU Qin, ZHAO Xingquan, WANG Anxin

2024, 19(10):  1221-1229.  DOI: 10.3969/j.issn.1673-5765.2024.10.016

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Directed acyclic graph (DAG) is a visualization tool to construct causal hypotheses in causal inference, which can be used to control confounding bias in observational studies by screening the minimal adjustment subsets that need to be adjusted through the backdoor criterion. However, existing studies lack standardization in drawing DAGs and the quality of DAGs used in the literature varies, which causes application dilemmas. The emergence of the ESC-DAGs method provides a standardized process for constructing DAGs. Based on the basic idea of systematic review, ESC-DAGs extensively searches relevant literature and divides the construction process into three phases: mapping, translation, and integration. Firstly, a saturated DAG is constructed based on each retrieved study. The directed edges are screened in the graph according to the Hill criterion and the potential outcome framework, and finally, all the retained directed edges are integrated into one DAG. The ESC-DAGs method makes full use of the literature information and the expertise of researchers. It provides a reasonable and feasible criterion for applying DAGs, which has important guiding significance. This article presents the content of the ESC-DAGs method and elucidates the specific process of constructing a DAG using an example from a clinical study on stroke.

Exploration of Refined Teaching Management in Cerebrovascular Surgery of the Grade A Tertiary Hospitals

LIU Yijie

2024, 19(10):  1230-1232.  DOI: 10.3969/j.issn.1673-5765.2024.10.017

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With the intensification of population aging in China, the incidence of cerebrovascular diseases is increasing year by year, and the demand for cerebrovascular surgery professionals is also getting higher. Cerebrovascular surgery has the characteristics of many difficult and complex cases, which brings challenges to talent training. The goal of cerebrovascular surgery education is to cultivate high-quality applied medical talents. This article aims to achieve refined teaching management by applying the plan, do, check, action (PDCA) cycle, combined with innovative teaching resources and new teaching models, to adapt to the demand for high-quality training of cerebrovascular surgery professionals in the new era.

Application of the “Organ System-Based, Disease-Centric” Multidisciplinary Integrated Teaching Model in the Teaching of Cerebrovascular Diseases for Five-Year Clinical Medicine Undergraduate Students

CHE Fengli, TONG Yanna, HAN Zhenzhen, DUAN Honglian, GENG Xiaokun, ZHAO Xingquan

2024, 19(10):  1233-1238.  DOI: 10.3969/j.issn.1673-5765.2024.10.018

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Objective  To explore the application effect of the “organ system-based, disease-centric” multidisciplinary integrated teaching model in the teaching of cerebrovascular diseases for five-year clinical medicine undergraduate students.
Methods  Two classes of five-year clinical medicine undergraduate students of grade 2019 studying in Beijing Luhe Hospital, Capital Medical University from March to May 2023 were selected as the research objects. They were randomly divided into the experimental and control groups according to different teaching models. Both groups studied the chapter on cerebrovascular diseases. The control group was taught using the traditional teaching model, while the experimental group was taught using the “organ system-based, disease-centric” multidisciplinary integrated teaching model. The assessment indicators of teaching effect included students’ test scores, students’ evaluation of the classroom teaching quality, and the evaluation on the improvement of their ability. The teaching effect was evaluated after the completion of the teaching period.
Results  The theoretical assessment scores [(43.90±2.36) scores vs. (41.83±3.36) scores, P=0.008], practical assessment scores [(43.67±2.16) scores vs. (41.70±3.01) scores, P=0.005], and overall scores [(87.57±3.30) scores vs. (83.53±5.43) scores, P=0.001] of the experimental group were all higher than those of the control group. Additionally, the evaluation scores of the experimental group on the classroom teaching quality (including quality requirements and overall scores) and various dimensions of the improvement of their ability (such as classroom participation, cultivation of learning interest, expansion of clinical thinking, improvement of self-learning ability, and improvement of communication and teamwork skills) were higher than those of the control group. The differences were statistically significant (all P<0.05). 
Conclusions  The application of the “organ system-based, disease-centric” multidisciplinary integrated teaching model in the teaching of cerebrovascular diseases for five-year clinical medicine undergraduate students can improve their theoretical knowledge and clinical practice skills.