Table of Content

20 June 2025, Volume 20 Issue 6

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Multi-omics Research in Cerebrovascular Disease

ZHANG Jie, LI Hao, CHENG Si

2025, 20(6):  657-662.  DOI: 10.3969/j.issn.1673-5765.2025.06.001

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Currently, cerebrovascular disease still faces challenges in elucidating mechanisms, constructing specialized cohorts, and developing new drugs. The advancement of multi-omics has provided a driving force for understanding the complex pathophysiological regulatory mechanisms, optimizing disease classification and diagnosis, enhancing prognosis prediction capabilities, and advancing the new drug development process. China has established the STROMICS database, a multi-omics and multimodal database of cerebrovascular disease at the ten-thousand-person level. China will further develop a more comprehensive multi-omics cohort for cerebrovascular disease and advance multi-omics research through interdisciplinary approaches such as Mendelian randomization. This will provide methods to deepen the understanding of the regulatory mechanisms underlying cerebrovascular disease and to facilitate new drug development.

Multi-omics Research and Novel Drug Development for Cerebrovascular Diseases

CHENG Si

2025, 20(6):  663-663. 

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Development and Extended Applications of Standardized Processes for Genome-Wide Association Studies

XU Zhe, SHI Yanfeng, ZHANG Jie, JIANG Minghui, LIU Yang, LI Hao, LIAO Xiaoling, CHENG Si

2025, 20(6):  664-674.  DOI: 10.3969/j.issn.1673-5765.2025.06.002

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Objective  To develop standardized workflow for GWAS and multi-omics analysis frameworks, providing an efficient analytical pipeline for pharmaceutical reverse engineering of cerebrovascular diseases using multi-omics cohorts.
Methods  A modular analysis system was constructed based on international GWAS quality control standards and multi-omics integration strategies. Pre-GWAS data quality control module: this module performed stringent quality control on sample and variant call rates, population genetic structure and stratification, and kinship. In the population composed of qualified samples, genetic variants with a minor allele frequency＞0.5% were retained for GWAS. Association analysis module: using software such as PLINK, SAIGE, and Regenie, GWAS was performed utilizing generalized linear models and generalized linear mixed models. The quality of GWAS was evaluated by the genome inflation coefficient and quantile-quantile plots. The module was tested using whole-genome sequencing and clinical data from the China national stroke registry Ⅲ. Multi-omics analysis module: this module integrated polygenic risk score, cross-cohort meta-analysis, Mendelian randomization, and colocalization analysis procedures, providing support for molecular mechanism interpretation and target screening using GWAS results.
Results  The pre-GWAS data quality control module established in this study conducts pre-GWAS quality control and assessment from the aspects of genetic data quality and population genetics. After quality control, 9632 and 7265 samples were included in the GWAS of baseline TG levels and 3-month post-stroke mortality phenotypes, respectively. The GWAS results showed that the trends of Manhattan plots obtained from different software were similar. However, compared to PLINK and Regenie, SAIGE software offered more appropriate correction and relatively robust statistical testing, especially when case-control samples were biased. In the multi-omics analysis module, standardized analysis processes including polygenic risk score, meta-analysis, Mendelian randomization, and colocalization analysis were developed to enable in-depth exploration of GWAS results.
Conclusions  The GWAS standardization processes established in this study are characterized by modularity and high scalability, enabling comprehensive analysis of complex phenotypes and multi-omics data. These processes provide a methodological foundation for exploration of pharmaceutical reverse engineering based on genetic association.




Causal Relationship between Lipid Metabolome and Stroke: A Systematic Mendelian Randomization Study

JIANG Minghui, XU Zhe, SHI Yanfeng, ZHANG Jie, LI Hao, CHENG Si

2025, 20(6):  675-685.  DOI: 10.3969/j.issn.1673-5765.2025.06.003

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Objective  Abnormal lipid metabolism is closely associated with the occurrence and development of stroke. This study aims to explore the causal associations between lipid metabolome and stroke as well as its subtypes, and to analyze the impact of lipoprotein components on stroke.
Methods  Based on the GWAS of 213 lipid metabolites, as well as any stroke (AS), any ischemic stroke (AIS), and its three subtypes—large artery stroke (LAS), cardioembolic stroke (CES), and small vessel stroke (SVS), univariate Mendelian randomization (MR) methods were used to screen the lipid metabolites that have potential causal relationships with stroke. On this basis, multivariate MR methods were employed to integrate the genetic correlations among lipid metabolites, further identifying those with independent causal effects. 
Results  In the univariate MR analysis, 16, 58, and 58 lipid metabolites were identified as having potential causal associations with AS, AIS, and LAS, respectively, while only one lipid metabolite was found to be associated with each of CES and SVS. There were widespread genetic correlations among these lipid metabolites. Through further screening by multivariate MR analysis, 11, 4, and 39 lipid metabolites with high-confidence associations with AS, AIS, and LAS were identified, respectively. Among them, small-low density lipoprotein (S-LDL), medium-low density lipoprotein (M-LDL), and the ratio of phospholipids to total lipids in small-high density lipoproteins had potential protective effects on stroke and its subtypes; while lipid components such as cholesterol and cholesterol esters in S-LDL and M-LDL were significantly associated with an increased risk of LAS.
Conclusions  Lipid metabolites exert the most significant effect on LAS, and the proportion of cholesterol and phospholipids in lipoprotein particles plays differentiated roles in the occurrence and development of stroke.




Research on Drug Repositioning across Different Ethnic Groups and Stroke Subtypes Driven by Stroke-Associated Genes

ZHANG Jie, GOU Lan, LI Lanxin, XU Zhe, SHI Yanfeng, JIANG Minghui, LI Hao, CHENG Si

2025, 20(6):  686-698.  DOI: 10.3969/j.issn.1673-5765.2025.06.004

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Objective  Given the challenges of drug transformation for stroke-associated genes and the genetic heterogeneity across different ethnic groups and stroke subtypes, this study aims to perform drug repositioning analysis targeting these genes based on improved functional annotation of stroke-associated genes, to identify potential cross-indication drug candidates for stroke treatment.
Methods  This paper systematically searched the GWAS Catalog database to identify stroke-associated single nucleotide variants (SNVs) along with their corresponding literature. The search time range was set from the establishment of the database to April 27, 2025. Concurrently, PubMed was searched for stroke-associated cohort studies, case-control studies, and meta-analyses published between March 1, 2018 and April 27, 2025. Additional stroke-associated SNVs were extracted from these publications. After merging and filtering these records, the final set of included SNVs and literature was obtained. Based on the mapping relationships between SNVs and genes, the set of stroke-associated genes was subsequently defined. Drug repositioning analysis targeting these genes was performed using the GREP software (version 1.0.0).
Results  A total of 1661 stroke-associated SNVs were retrieved from the GWAS Catalog database across 49 publications, while 77 publications were identified from PubMed. After screening, ‌835 stroke-associated SNVs‌ spanning ‌338 genes‌ were ultimately included from ‌38 publications‌, with pooled samples totaling ‌11 714 626 subjects‌. The drug repositioning analysis revealed that the most significantly enriched drug classes for stroke-associated genes were as follows. For Africans, East Asians, Europeans, and cross-ethnic groups, the most significantly enriched drug classes were anti-neoplastic agents (OR 25.75, P=1.51×10^-2), other respiratory system products (OR 84.08, P=1.71×10^-2), other hematological agents (OR 36.15, P=2.70×10^-4), and other alimentary tract and metabolism products (OR 12.67, P=3.09×10^-3), respectively. In contrast, no significantly enriched drug classes were identified for stroke-associated genes in Hispanics and South Asians. For ischemic stroke, cardioembolic stroke, and small vessel stroke, the most significantly enriched drug classes were other hematological agents (OR 31.31, P=4.00×10^-4), other hematological agents (OR 41.10, P=3.12×10^-2), and ectoparasiticides (OR 50.35, P=2.68×10^-2), respectively. No significantly enriched drug classes were identified for any stroke or large artery stroke-associated genes. Additionally, it was found that stroke-associated genes were also enriched in drug classes such as drugs for constipation, antithrombotic agents, β-blockers, and gynecological anti-infectives and antiseptics.
Conclusions  The enriched drug classes for genes associated with different ethnic groups and stroke subtypes demonstrate marked variability. Specifically, significant enrichment is identified in several drug classes that are not conventionally implicated in stroke therapy, including anti-neoplastic agents, other respiratory system products, other alimentary tract and metabolism products, gynecological anti-infectives and antiseptics, and ectoparasiticides.




Drug-Target Mendelian Randomization Based on Multi-omics Data and Its Application in the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases

FAN Zhe, JIANG Minghui, CHENG Si, LIU Siyang

2025, 20(6):  699-709.  DOI: 10.3969/j.issn.1673-5765.2025.06.005

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Cardiovascular and cerebrovascular diseases are leading causes of death and disability worldwide, necessitating sustained drug development efforts to alleviate the substantial burden on society and healthcare systems. Drug‑target Mendelian randomization (MR) employs cis protein quantitative trait loci as instrumental variables to investigate causal relationships between protein targets and disease outcomes in observational studies, thereby providing robust preclinical evidence for drug development. In the field of cardiovascular and cerebrovascular diseases, this approach has been widely applied for target screening, adverse reaction assessment, and drug repurposing. This article systematically elaborates the analytical framework of drug‑target MR (including instrumental variable selection, effect estimation, sensitivity analysis, adverse reactions, and mediation analysis), summarizes the research progress of drug targets such as lipid‑lowering and anti‑inflammatory in the treatment of cardiovascular and cerebrovascular diseases and discusses its limitations and future directions in specialized disease cohort studies. These insights aim to inform the discovery of novel drug targets for cardiovascular and cerebrovascular diseases.

Applications and Challenges of Integrating Artificial Intelligence with Clinical and Multi-omics Data in Stroke Prevention, Treatment, and Pharmaceutical Research and Development

GOU Lan, JIANG Minghui, JIANG Yong, LIAO Xiaoling, LI Hao, ZHANG Jie, CHENG Si

2025, 20(6):  710-717.  DOI: 10.3969/j.issn.1673-5765.2025.06.006

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Stroke is the leading global cause of death and disability. The research paradigm that integrates artificial intelligence (AI) with clinical and multi-omics data provides novel solutions for the precision prevention and treatment of stroke. By integrating and analyzing clinical and multi-omics data, AI technology enhances the identification of high-risk populations, optimizes early diagnosis and risk assessment, enables precise subtyping of stroke, facilitates the screening of potential drug targets, and constructs prognostic prediction models. However, critical challenges, such as insufficient multi-omics resources, difficulties in multi modal data integration, and limited interpretability of algorithms, remain major bottlenecks in clinical translation. This article reviews the advances and challenges in AI-driven integration of clinical and multi-omics data in stroke prevention and treatment as well as pharmaceutical research and development.



The Relationship between Carotid Pulse Wave Velocity, Serum Lp-PLA2, NRG-1, and Acute Ischemic Stroke with Hypertension

WANG Yun, MI Yaru, DENG Heping, ZHANG Bo

2025, 20(6):  718-727.  DOI: 10.3969/j.issn.1673-5765.2025.06.007

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Objective  To investigate the relationship between carotid pulse wave velocity (PWV), serum lipoprotein-associated phospholipase (Lp-PL) A2, and neuregulin-1 (NRG-1) with large artery atherosclerosis (LAA)-type acute ischemic stroke (AIS) with hypertension.
Methods  AIS patients with hypertension admitted to the Hebei Medical University Third Hospital from August 2022 to August 2024 were prospectively and consecutively included as the study group, and patients with hypertension alone were selected as the control group. The baseline data of patients in the study group and the control group were compared. The logistic regression model was used for multivariate analysis of hypertension combined with AIS. In the study group, patients were divided into mild (NIHSS score<5), moderate (5≤NIHSS score≤15), and severe (NIHSS score>15) groups based on neurological deficits, as classified by NIHSS score. The baseline data of patients in the three groups were then compared. The Pearson correlation coefficient was used to analyze the correlation between pulse wave velocity at the beginning of systole (PWV-BS), pulse wave velocity at the end of systole (PWV-ES), Lp-PLA2, NRG-1, and NIHSS score. The logistic regression model was used for multivariate analysis of the severity of neurological deficit in AIS patients with hypertension. 
Results  A total of 172 AIS patients with hypertension were included in the study group and 103 patients with hypertension alone were included in the control group. The multivariate analysis of logistic regression model showed that the levels of Lp-PLA2 (OR 1.031, 95%CI 1.017-1.045, P＜0.001), PWV-BS (OR 1.947, 95%CI 1.232-3.079, P=0.004), and PWV-ES (OR 2.218, 95%CI 1.567-3.138, P＜0.001) in the study group were higher than those in the control group, while the level of NRG-1 (OR 0.994, 95%CI 0.990-0.997, P＜0.001) was lower than that in the control group. Among the 172 AIS patients with hypertension in the study group, there were 68 patients in the mild group, 81 patients in the moderate group, and 23 patients in the severe group. Pearson correlation analysis showed that PWV-BS (r=0.631, P＜0.001), PWV-ES (r=0.599, P＜0.001), and Lp-PLA2 (r=0.489, P＜0.001) were positively correlated with NIHSS score, while NRG-1 was negatively correlated with NIHSS score (r=-0.485, P＜0.001). Multivariate analysis of the logistic regression model showed that the duration of hypertension in the moderate and severe groups (OR 40.469, 95%CI 2.915-561.898, P=0.006; OR 160.155, 95%CI 10.357-2476.616, P＜0.001), Lp-PLA2 (OR 1.154, 95%CI 1.039-1.282, P=0.007; OR 1.191, 95%CI 1.069-1.328, P=0.002), PWV-BS (OR 23.275, 95%CI 1.135-477.237, P=0.041; OR 79.267, 95%CI 3.158-1989.561, P=0.008), and PWV-ES (OR 99.259, 95%CI 3.367-2926.000, P=0.008; OR 203.017, 95%CI 6.212-6634.497, P=0.003) were higher than those in the mild group, while the level of NRG-1 (OR 0.980, 95%CI 0.964-0.996, P=0.014; OR 0.975, 95%CI 0.957-0.993, P=0.007) was lower than that in the mild group.  
Conclusions  PWV-BS, PWV-ES, and Lp-PLA2 levels were significantly higher and NRG-1 level was significantly lower in AIS patients with hypertension. The duration of hypertension, and the levels of Lp-PLA2, PWV-BS, PWV-ES and NRG-1 were related to the severity of neurological deficits in AIS patients with hypertension.


The Relationship between Ultrasonographic Features of Carotid Web and Ischemic Stroke

GUO Li, SONG Xintong, ZHANG Guanyi, ZHANG Qian, JU Yi, ZHAO Xingquan

2025, 20(6):  728-733.  DOI: 10.3969/j.issn.1673-5765.2025.06.008

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Objective  To evaluate the structural features of the carotid web by vascular ultrasound and explore the relationship with ischemic stroke.
Methods  This retrospective study consecutively enrolled patients with CTA-confirmed carotid web and unilateral carotid territory ischemic stroke at Beijing Tiantan Hospital, Capital Medical University from January 2021 to June 2024. Patients were divided into the ipsilateral stroke group and the contralateral stroke group based on the presence of ipsilateral ischemic stroke. Vascular ultrasound was used to measure carotid web length, thickness, and angulation relative to the vessel wall. Additional parameters, including laterality, location, attachment site, mobility with blood flow, orientation relative to flow direction, and presence of thrombosis around the carotid web were documented. Structural differences in carotid webs were compared between the two groups. 
Results  This study enrolled 102 carotid web patients, with 70 in the ipsilateral stroke group and 32 in the contralateral stroke group. The incidence of limb weakness and motor impairment was significantly higher in the ipsilateral stroke group (54.3% vs. 34.4%, P=0.047), whereas headache was more frequently observed in the contralateral stroke group (15.6% vs. 0, P=0.003). Ultrasonographic findings demonstrated a significantly higher prevalence of thrombosis around the carotid web in the ipsilateral stroke group compared to the contralateral group (84.3% vs. 50.0%, P<0.001). However, there were no significant differences in the laterality, location, attachment site, length, thickness, angulation relative to the vessel wall, mobility with blood flow, and orientation relative to the flow direction of the carotid web between the two groups (all P>0.05).
Conclusions  This study demonstrated that thrombosis around the carotid web may be associated with ipsilateral ischemic stroke.


Analysis and Prediction of the Trend in Disease Burden of Ischemic Stroke among Chinese Young Adults

WANG Xiaojun, YANG Keke, WU Jianheng, LIN Duo, LI Chenwei, PENG Huiyuan

2025, 20(6):  734-745.  DOI: 10.3969/j.issn.1673-5765.2025.06.009

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Objective  To analyze the changes in the disease burden of ischemic stroke among Chinese young adults aged 20-49 years from 1990 to 2021, and to predict the incidence of ischemic stroke from 2022 to 2035. 
Methods  Based on the data from the global burden of disease 2021 database on ischemic stroke among Chinese young adults, the disease prevalence was quantified using age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR). The burden of the disease was quantified using disability-adjusted life years (DALYs) and age-standardized DALYs rate (ASDR). This paper analyzed the trends in DALYs associated with risk factors of ischemic stroke among Chinese young adults. The Segmented segmentation model was used to calculate the annual percentage change, and the fitted regression model was used to calculate the estimated annual percentage change (EAPC) to assess the disease trend, while also predicting the incidence rate and number of cases of ischemic stroke among young adults from 2022 to 2035. 
Results  The ASIR of ischemic stroke among Chinese young adults has increased from 18.28 (95%UI 10.85-28.23)/100 000 in 1990 to 24.93 (95%UI 16.09-36.88)/100 000 in 2021, with an EAPC of 0.82% (95%CI 0.71%-0.92%). The ASMR has decreased from 2.63 (95%UI 2.13-3.25)/100 000 in 1990 to 1.88 (95%UI 1.49-2.33)/100 000 in 2021, with an EAPC of -1.09% (95%CI -1.25% - -0.93%). The ASDR has decreased from 182.87 (95%UI 150.95-221.94)/100 000 in 1990 to 150.68 (95%UI 122.19-180.70)/100 000 in 2021, with an EAPC of -0.64% (95%CI -0.74%--0.54%). The prediction models indicate that by 2035, the ASIR of ischemic stroke among Chinese young adults will rise to 25.40 (95%CI 22.41-28.40)/100 000, affecting an estimated 132 303 (95%CI 116 701-147 906) cases. Among the risk factors, metabolic factors have the greatest impact on DALYs in the young stroke patients, followed by behavioral factors.
Conclusions  From 1990 to 2021, the ASIR of ischemic stroke among Chinese young adults showed an upward trend, while the ASDR and ASMR showed a downward trend. By 2035, the disease burden of ischemic stroke among Chinese young adults will still be significant, emphasizing the importance of focusing on the prevention and control of metabolic factors in the future.




Observation on Clinical Characteristics, Treatment, and Outcomes in Pregnant Patients with Acute or Previous Hemorrhage from Cerebral Arteriovenous Malformations

LIU Tong, YIN Zihan, ZHANG Zhongji, ZHANG Yan, LIU Xingju

2025, 20(6):  746-752.  DOI: 10.3969/j.issn.1673-5765.2025.06.010

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Objective  To investigate the clinical characteristics, intervention timing, intervention methods, and maternal-neonatal outcomes in pregnant patients with acute or previous hemorrhage from cerebral arteriovenous malformation (AVM).
Methods  This study retrospectively included pregnant patients with acute AVM hemorrhage treated at Beijing Tiantan Hospital, Capital Medical University from January 2010 to December 2021. Additionally, pregnant patients without hemorrhage during the current pregnancy but with a history of AVM hemorrhage and residual malformations after interventional treatment were included for comparison. Collected information included age, pregnancy/delivery details (obstetric history, gestational weeks at symptom onset/delivery, delivery mode, underlying diseases, and pregnancy complications), admission symptoms, AVM-related characteristics (Spetzler-Martin grade, location, bleeding site), treatment details (pre-pregnancy, during pregnancy, and puerperium), and maternal-neonatal outcomes (maternal outcomes assessed using the mRS score, neonatal outcomes assessed using the Apgar score).
Results  A total of 18 patients were enrolled, including 12 pregnant patients with acute AVM hemorrhage and 6 pregnant patients with previous AVM hemorrhage. The age range of the 18 patients was 23-34 years, with a median age of 29.0 (27.5-31.0) years. The median gestational weeks at symptom onset and delivery were 22.0 (16.5-30.0) weeks and 32.0 (28.0-36.0) weeks, respectively. The Spetzler-Martin grading showed that grades IV-V accounted for the highest proportion (44.4%, 8/18), supratentorial malformations accounted for 83.3% (15/18). Among the 12 pregnant patients with acute AVM hemorrhage, 83.3% (10/12) experienced hemorrhage during the mid-to-late trimester of pregnancy (gestational weeks≥13 weeks). For patients receiving emergency AVM surgical treatment, the maternal favorable outcome rate was 75.0% (6/8), and the neonatal favorable outcome rate was 75.0% (6/8). For patients receiving conservative management, the maternal favorable outcome rate was 75.0% (3/4), and the neonatal favorable outcome rate was 50.0% (2/4). For patients delivered via cesarean section, the maternal favorable outcome rate was 88.9% (8/9), and the neonatal favorable outcome rate was 88.9% (8/9). For patients undergoing artificial abortion, the maternal favorable outcome rate was 33.3% (1/3). For pregnant patients with previous AVM hemorrhage receiving conservative management, the maternal favorable outcome rate was 83.3% (5/6), and the neonatal favorable outcome rate was 83.3% (5/6). Cesarean section was performed in 5 cases (maternal favorable outcome in 3 cases, neonatal favorable outcome in 4 cases), artificial abortion was performed in 1 case (maternal favorable outcome, neonatal death).
Conclusions  Acute hemorrhage in pregnant patients with cerebral AVMs predominantly occurs in the mid-to-late trimester. Proactive neurosurgical intervention after multidisciplinary evaluation is recommended. For pregnant patients with previous AVM hemorrhage, conservative management of AVM with multidisciplinary perinatal assessment is feasible, and cesarean section is recommended as the delivery mode.


Meta-Analysis of the Efficacy and Safety of Butylphthalide Sequential Treatment in Acute Ischemic Stroke

HU Yanqin, WANG Shuo, ZHAO Taoli, GUO Dongxing, LI Shen, JIN Zhenbo

2025, 20(6):  753-761.  DOI: 10.3969/j.issn.1673-5765.2025.06.011

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Objective   To systematically evaluate the efficacy and safety of butylphthalide sequential treatment in acute ischemic stroke.
Methods  This study searched English databases such as PubMed, Embase, and Cochrane Library, as well as Chinese databases such as Wanfang, CNKI, and VIP. RCTs of butylphthalide sequential treatment in acute ischemic stroke were included, with the search period covering the period from the inception of the databases to June 30, 2024. The Cochrane RevMan bias risk assessment tool was used to evaluate the quality of the included RCTs. Baseline information, treatment details, and efficacy indicators [rate of good prognosis (mRS score 0-2) at 90 days, post-treatment neurological status (assessed by NIHSS score), post-treatment functional status (assessed by mRS score), and post-treatment activity of daily living (ADL) score], and safety indicators (adverse events and serious adverse events) were extracted. Meta-analysis was conducted using RevMan 5.3 software to calculate the OR values and their 95%CI for categorical variables, and the standardized mean difference (SMD) values and their 95%CI for continuous data. 
Results  This study included a total of 8 RCTs, with 3 reported in English and 5 in Chinese. It involved 1911 patients, including 932 in the control group and 979 in the experimental group. Meta-analysis showed that compared to conventional treatment, butylphthalide sequential treatment improved the 90-day good prognosis rate in acute ischemic stroke patients (OR 1.41, 95%CI 1.11-1.77, P=0.004), reduced the post-treatment mRS score (SMD -0.85, 95%CI -1.09--0.60, P<0.001) and NIHSS score (SMD -0.95, 95%CI -1.13--0.77, P<0.001), and increased the post-treatment ADL score (SMD 1.26, 95%CI 1.05-1.46, P<0.001). There was no statistically significant difference between the two groups in the incidence of adverse events (OR 0.97, 95%CI 0.76-1.24, P=0.80) or serious adverse events (OR 0.83, 95%CI 0.59-1.16, P=0.27).
Conclusions  Sequential treatment with butylphthalide can improve the prognosis, neurological function, and ADL of patients with acute ischemic stroke without increasing the incidence of adverse events.


Comparison of the Efficacy between Tirofiban Combined with Argatroban and Tirofiban in the Treatment of Acute Branch Atheromatous Disease

LUO Rong, SHI Haicun

2025, 20(6):  762-768.  DOI: 10.3969/j.issn.1673-5765.2025.06.012

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Objective  To explore the effect of tirofiban combined with argatroban in the treatment of acute branch atheromatous disease (BAD). 
Methods  Patients with mild BAD treated at the Yancheng Third People’s Hospital from January 2022 to May 2024 were retrospectively included. According to the treatment plan, patients were divided into the tirofiban combined with argatroban group (dual-pump group) and the tirofiban group. Early neurological deterioration (END) was defined as an increase in NIHSS score of≥2 points or an increase in motor function score of≥1 point within 7 days of onset. A good prognosis was defined as a mRS score of＜2 at 3 months after onset. 
Results  A total of 83 patients with mild BAD were included, with 31 patients in the dual-pump group and 52 patients in the tirofiban group. The baseline clinical data between the two groups showed no statistically significant difference. The proportion of END occurrence in the dual-pump group was statistically lower than that in the tirofiban group [6.5% (2/31) vs. 26.9% (14/52), P=0.046]. The proportion of good prognosis patients in the dual-pump group was statistically higher than that in the tirofiban group [96.8% (30/31) vs. 76.9% (40/52), P=0.036]. In the dual-pump group, one patient developed oral mucosal bleeding, while no intracranial hemorrhage events occurred in all patients. Multivariate logistic regression showed that tirofiban combined with argatroban was the treatment of BAD independent influencing factors for non-END and good prognosis (P<0.05).
Conclusions  The combination of tirofiban and argatroban in treating mild BAD patients can reduce the incidence of END, increase the proportion of patients with good prognosis at 3 months after onset, and does not increase the risk of intracranial hemorrhage.


A Case of Isolated Symptomatic Basilar Artery Stenosis with Imaging Reversal

LU Qingli, SUN Chao, SONG Chensheng, LIU Guozheng, LIU Pei, LIU Yan, CHANG Qiaoqiao, LIN Xuemei, WU Songdi

2025, 20(6):  769-774.  DOI: 10.3969/j.issn.1673-5765.2025.06.013

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There is limited research on isolated symptomatic basilar artery stenosis (ISBAS), and the treatment strategies remain unclear. This article reported the process of diagnosis and treatment of an ISBAS patient whose imaging findings ultimately reversed after six months of aggressive medical therapy. The patient presented with mild neurological deficits at the onset of the disease, but the condition rapidly deteriorated after admission. Vascular examination revealed subtotal occlusion of the basilar artery. The patient refused endovascular treatment and was given dual antiplatelet therapy and high-intensity statin therapy for six months. Follow-up MRA examinations at 3 and 6 months showed progressive improvement in basilar artery stenosis, ultimately leading to its reversal.



Research Progress on Lipoprotein(a) and Ischemic Stroke

HE Xun, CHEN Xinyi, HU Jie, LI Jiaxuan, JIA Xinhui, WU Juncang

2025, 20(6):  775-780.  DOI: 10.3969/j.issn.1673-5765.2025.06.014

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Lipoprotein(a) [Lp(a)] is a highly heritable lipoprotein whose role in cardiovascular disease has been extensively studied. However, its association with ischemic stroke remains incompletely understood. This review summarizes the biological characteristics of Lp(a) and its variability across different ethnicities, geographic regions, age groups, and genders. It also explores the relationship between Lp(a) and genetic factors, highlighting its role in the onset and recurrence of ischemic stroke. Special emphasis is placed on the pathophysiological mechanisms of Lp(a) in atherosclerosis, inflammatory responses, and thrombogenesis. While conventional lipid-lowering therapies have shown limited efficacy in reducing Lp(a) levels, emerging strategies such as RNA-targeted therapies demonstrate promising potential in lowering Lp(a). These novel therapeutic strategies provide new targets and ideas for reducing stroke risk.

Neurological and Extra-Neurological Symptoms in Monogenic Cerebral Small Vessel Disease: Diagnostic Implications

JIANG Junjie, WANG Mengwen, WAN Yan, HU Bo

2025, 20(6):  781-789.  DOI: 10.3969/j.issn.1673-5765.2025.06.015

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Cerebral small vessel disease (CSVD) is a group of neurological diseases with complex etiologies, mainly manifesting as ischemic or hemorrhagic stroke, cognitive impairment, emotional and psychiatric abnormalities, and gait disorders. Neuroimaging features include recent subcortical infarcts, enlarged perivascular spaces, cerebral microbleeds, intracranial hemorrhage, brain atrophy, lacunes of presumed vascular origin, and white matter lesions. Monogenic CSVD represents a rare subtype, accounting for 1% to 5% of all cases, with dozens of pathogenic genes reported to date. In addition to the common clinical and imaging manifestations of CSVD, monogenic CSVD often has specific symptoms, particularly extra-neurological symptoms, which have a strong indicative role in diagnosis. Given the time-consuming and challenging situation of genetic testing for CSVD-related genes, a comprehensive understanding of the neurological and extra-neurological symptoms of monogenic CSVD can facilitate early diagnosis and treatment. This article aims to summarize the neurological symptoms, extra-neurological symptoms, neuroimaging features, and their value for clinical diagnosis in monogenic CSVD.



Advances in Adenosine-Induced Cardiac Arrest and Hypotension-Assisted Intracranial Aneurysm Clipping

LIU Changtong, TONG He, SONG Guohong

2025, 20(6):  790-796.  DOI: 10.3969/j.issn.1673-5765.2025.06.016

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Although interventional surgery is the preferred treatment for intracranial aneurysms, microsurgery remains indispensable for complex aneurysms. The key challenge in surgery is to achieve safe aneurysm clipping while maintaining patency of the parent artery and its branches. Adenosine-induced transient cardiac arrest and hypotension can rapidly reduce aneurysmal blood flow, optimize anatomical conditions, and enhance the safety and efficacy of clipping. Compared to traditional methods, adenosine administration is simpler, non-invasive, fast-acting, rapidly metabolized, and associated with fewer adverse reactions, showing potential application in intracranial aneurysm clipping. However, individualized dose regulation and potential cardiovascular risks require further investigation. This article reviews the mechanisms, advantages, disadvantages, indications, contraindications, administration methods, and safety of adenosine in intracranial aneurysm microsurgery, providing a more comprehensive reference for clinical application.