Journal of Investigative Medicine最新文献

{"title":"Association between elevated adiponectin levels and 5-year risk of clinical outcomes in patients with ischaemic stroke.","authors":"Siding Chen, Fanzhen Lin, Jinfeng Yin, Xiaomeng Yang, Xia Meng, Yongjun Wang, Yong Jiang","doi":"10.1136/svn-2024-003517","DOIUrl":"https://doi.org/10.1136/svn-2024-003517","url":null,"abstract":"<p><strong>Background: </strong>The role of adiponectin (ADPN) in stroke remains debatable, despite its significant impact as a major adipocytokine on cardiovascular (CV) diseases. This study aimed to assess the association between ADPN and 5-year mortality, functional outcome and recurrence in Chinese individuals with first ischaemic stroke (IS).</p><p><strong>Methods: </strong>This prospective, multicentre study recruited IS patients from 201 hospitals in China between August 2015 and March 2018. Multivariable Cox regression evaluated ADPN's association with mortality/recurrence, while logistic regression analysed poor functional outcomes (modified Rankin Scale score 3-6 and 3-5).</p><p><strong>Results: </strong>Among 8086 patients (median age 62; 31.8% female), there were 710 deaths, 1134 recurrences and 1223 poor functional outcomes (modified Rankin Scale 3-6). Higher baseline ADPN levels were significantly associated with increased risk of 5-year non-CV mortality (adjusted HR _{Q4 vs Q1}=1.47 (95% CI 1.10 to 1.96), p=0.06) after adjustment for age, sex, body mass index and National Institutes of Health Stroke Scale. No independent associations were found between ADPN and CV mortality, stroke recurrence or poor functional outcome. Subgroup analysis revealed a significant association between ADPN and 5-year mortality from various causes among patients with cardioembolism (adjusted HR _{Q4 vs. Q1}=2.39 (95% CI 1.24 to 4.62), p=0.007) and large artery atherosclerosis (adjusted HR _{Q4 vs Q1}=2.16 (95% CI 1.34 to 3.47), p=0.004).</p><p><strong>Conclusions: </strong>Elevated baseline ADPN levels were independently associated with increased 5-year non-CV mortality in Chinese IS patients, especially among those with mild neurological impairment. These findings suggest ADPN may serve as a prognostic biomarker for systemic vulnerability after stroke.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of futile recanalisation in patients with large infarct: a post-hoc analysis of the ANGEL-ASPECT trial.","authors":"Tingyu Yi, Xiaochuan Huo, Xiaohui Lin, Mengxing Wang, Yan-Min Wu, Zhinan Pan, Xiufen Zheng, Ding-Lai Lin, Yuesong Pan, Zhongrong Miao, Wenhuo Chen","doi":"10.1136/svn-2024-003382","DOIUrl":"10.1136/svn-2024-003382","url":null,"abstract":"<p><strong>Background: </strong>Studies on futile recanalisation after endovascular therapy (EVT) for anterior circulation large vessel occlusion with large infarct were scarce. The present study aimed to explore the incidence and independent predictors of futile recanalisation in patients with large infarct.</p><p><strong>Methods: </strong>This is a post-hoc analysis of the ANGEL-Alberta Stroke Program Early CT (ASPECT) trial. A favourable outcome was defined as a 90-day modified Rankin Scale score of 0-3; successful reperfusion was defined as extended thrombolysis in cerebral infarction 2b, 2c and 3 on final angiogram; and futile recanalisation was defined as unfavourable outcome despite successful reperfusion. We performed multivariate analysis to identify the predictors of futile recanalisation after EVT in patients with large infarct.</p><p><strong>Results: </strong>A total of 183 patients were included: 91 (49.7%) patients had futile recanalisation and 92 (51.3%) had meaningful recanalisation. In multivariable logistic regression analysis, nonmodifiable factors included older age (age ≥68 years, OR=3.4, 95%CI 1.5 to 7.7, p= 0.003), female sex (OR=2.78, 95%CI 1.28 to 7.27, p=0.01), higher National Institutes of Health Stroke Scale score (NIHSS ≥16, OR=3.1, 95%CI 1.2 to 8.3, p=0.035), diabetes (OR=3.1, 95%CI 1.2 to 8.3, p=0.017) and symptomatic intracranial haemorrhage (sICH) (OR=9.1, 95%CI 1.0 to 80.7, p=0.049), and modifiable factors included larger final infarct volume (FIV ≥174.7, OR=6.2, 95%CI 2.5 to 15.7, p<0.001) and postoperative respiratory failure (OR=14.1, 95%CI 1.6 to 124.8, p=0.018), which were independent predictors of futile recanalisation.</p><p><strong>Conclusions: </strong>Futile recanalisation occurred in approximately half of patients who had an acute stroke with large infarct after EVT in the ANGEL-ASPECT trial. Nonmodifiable factors that included old age, high baseline NIHSS score, diabetes mellitus, sICH and large FIV, and modifiable factors that included respiratory failure were independent predictors of futile recanalisation after EVT for large ischaemic strokes. Stroke-related pneumonia control may improve prognosis.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous thrombolysis versus early antiplatelet therapy in acute ischaemic stroke with small artery occlusion.","authors":"Ke Zhang, Hongbing Liu, Ce Zong, Yapeng Li, Kai Liu, Yusheng Li, Jing Yang, Bo Song, Yuming Xu, Yuan Gao","doi":"10.1136/svn-2025-004309","DOIUrl":"https://doi.org/10.1136/svn-2025-004309","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of intravenous thrombolysis (IVT) versus early antiplatelet therapy (APT) in small artery occlusion (SAO) stroke remains debated.</p><p><strong>Methods: </strong>Ischaemic stroke (IS) patients with SAO who received IVT or early APT without IVT≤4.5 hours from stroke onset were screened from a prospective multicentre IS registry study from 1 January to 1 June 2021. The primary outcome was unfavourable functional outcome (FO) at 3 months. The secondary outcome was early neurological deterioration (END). The safety outcome was symptomatic intracerebral haemorrhage (sICH).</p><p><strong>Results: </strong>There were 1125 SAO patients with 394 receiving IVT. 411 patients (36.5%) exhibited unfavourable FO, and sICH occurred in 3 cases (0.27%), all in IVT group, at the follow-up. END was observed in 213 patients (18.9%). After propensity score matching and multivariable adjustment, IVT significantly reduced the likelihood of unfavourable FO at 3 months (aOR 0.447, 95% CI 0.305 to 0.656), but no significant difference was found in END (aOR 0.867, 95% CI 0.569 to 1.321). Clustering analysis identified two distinct phenotypes: phenotype 0 (characterised by traditional cardiovascular risk factors) and phenotype 1 (marked by prominent inflammatory markers). A significant treatment-by-phenotype interaction was observed (p=0.002), with a comparable magnitude of benefit in phenotype 0 (aOR 0.405, 95% CI 0.244 to 0.673) compared with phenotype 1 (aOR 0.414, 95% CI 0.218 to 0.783).</p><p><strong>Conclusion: </strong>IVT significantly reduced the likelihood of unfavourable FO at 3 months in SAO patients but did not significantly reduce END. Patients with traditional risk factors may benefit more from IVT than those with elevated inflammatory markers.</p><p><strong>Trial registration number: </strong>ChiCTR2100045258.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardising the diagnosis and imaging of intracranial atherosclerotic stenosis in Asia: a call for regional consensus.","authors":"Jose C Navarro, Bonifacio C Pedregosa, Maria Socorro F Sarfati, Maria Teresa A Cañete, Johnny K Lokin, Marc C Molina, Allan A Belen, Robert N Gan","doi":"10.1136/svn-2025-004683","DOIUrl":"https://doi.org/10.1136/svn-2025-004683","url":null,"abstract":"","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macular choriocapillaris perfusion area: a potential biomarker of mild cognitive impairment in patients with cerebral small vessel disease.","authors":"Weitao Yu, Zeqi Shen, Weifen Zhang, Mengmeng Yue, Shouxuan Gao, Jiawei Ye, Wanmao Ni, Panpan Shen, Lujie Han, Shunyuan Guo, Jie Zheng, Liang Yu, Faliang Gao, Yu Geng, Chaoyang Hong, Sheng Zhang","doi":"10.1136/svn-2025-004139","DOIUrl":"https://doi.org/10.1136/svn-2025-004139","url":null,"abstract":"<p><strong>Aim: </strong>To develop and validate retinal vascular biomarkers for detecting mild cognitive impairment (MCI) in cerebral small vessel disease (CSVD) using swept-source optical coherence tomography angiography (SS-OCTA).</p><p><strong>Methods: </strong>Participants with MCI and normal cognition were prospectively enrolled from two ongoing cohorts (Dream-10 and FRESH-CSVD; NCT06164262 and NCT06431711). All participants underwent SS-OCTA and structural MRI (S-MRI). Individuals with Alzheimer's disease were excluded based on plasma biomarkers. Participants were split into development (January-August 2024) and temporal validation (September 2024-January 2025) cohorts. Feature selection was conducted using least absolute shrinkage and selection operator regression, followed by receiver operating characteristic analyses.</p><p><strong>Results: </strong>A total of 209 participants were included, with 48.8% (102/209) diagnosed with MCI. In the development cohort (n=136), the 3-6 mm macular choriocapillaris perfusion area (CCPA) of the left eye (oculus sinister, OS) showed superior diagnostic accuracy for MCI (AUC=0.906), outperforming S-MRI markers (all p<i><</i>0.05). Temporal validation confirmed diagnostic accuracy (AUC 0.902; sensitivity 88.6%, specificity 81.3%) with minimal performance drift (ΔAUC 0.002). Adding S-MRI markers did not significantly enhance diagnostic performance (p>0.05). Both 0-3 and 3-6 mm OS macular CCPA were significantly associated with cognitive decline (Mini-Mental State Examination, Montreal Cognitive Assessment and Clinical Dementia Rating Sum of Boxes; all p<i><</i>0.01), and mediation analyses suggested partial effects through white matter hyperintensity volume and right choroid plexus volume ratio.</p><p><strong>Conclusion: </strong>SS-OCTA-derived macular CCPA, especially in the 3-6 mm OS region, may serve as a promising and non-invasive biomarker for CSVD-related MCI. Further multicentre studies are needed to establish its clinical applicability.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I dose-escalation study of tenecteplase, a third-generation fibrinolytic agent, combined with neuronavigation-assisted stereotactic minimally invasive puncture, in patients with acute spontaneous deep cerebral haemorrhage.","authors":"Zhiyou Wu, Mingze Wang, Xiudan Bai, Jinyi Tang, Yang Ni, Shaozhi Zhao, Pengqi Wang, Qiheng He, Ran Huo, Yuming Jiao, Duolao Wang, Yong Cao","doi":"10.1136/svn-2025-004389","DOIUrl":"https://doi.org/10.1136/svn-2025-004389","url":null,"abstract":"<p><strong>Introduction: </strong>Tenecteplase (TNK) offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase. Moreover, its high specificity for fibrin may contribute to a reduction in haemorrhage complications. However, the safety, tolerability and efficacy of TNK, combined with neuronavigation-assisted stereotactic minimally invasive puncture, in patients with acute spontaneous deep cerebral haemorrhage remain unknown.</p><p><strong>Methods: </strong>We conducted a prospective, open-label phase I trial in a 3+3 dose escalation design to evaluate the safety and tolerability, and maximum tolerated dose (MTD) of TNK in patients with acute spontaneous basal ganglia or thalamic haemorrhage, with haematoma volumes ranging from 20 to 50 mL, combined with neuronavigation-assisted stereotactic minimally invasive puncture surgery (MIPS). During the dose-escalation phases of the trial, patients received intra-haematoma injection of TNK via a haematoma evacuation catheter every 24 hours after surgery until three doses were administered or any termination criteria were met (residual haematoma ≤10 mL or rebleeding event), with doses ranging from 0.001 to 0.003 and 0.009 mg per mL of haematoma volume. The primary safety endpoint was drug-related rebleeding during the dose escalation phases, while the primary efficacy endpoint was the mean drug-related haematoma clearance per dose.</p><p><strong>Results: </strong>In total, 12 patients were recruited. No drug-related rebleeding events at any dose escalation phase occurred. By the 24 hours after the last dose, the residual haematoma volume for each patient across all groups was reduced to less than 10 mL. The 0.009 mg TNK dose group achieved the highest mean haematoma clearance of 17.49 mL per dosing. The MTD was 0.009 mg/mL of haematoma volume in the dose escalation phase.</p><p><strong>Discussion and conclusion: </strong>TNK is well tolerated with encouraging signs of dissolving blood clots. Further exploration of TNK combined with neuronavigation-assisted stereotactic MIPS in patients with acute spontaneous deep cerebral haemorrhage is warranted.</p><p><strong>Trial registration number: </strong>NCT06668441.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual versus mono antiplatelet therapy within 72 hours after onset for mild ischaemic stroke or transient ischaemic attack: meta-analysis of randomised controlled trials.","authors":"Yingying Yang, Jinghan Zhu, Ying Gao, Yuesong Pan, Yilong Wang","doi":"10.1136/svn-2025-004143","DOIUrl":"https://doi.org/10.1136/svn-2025-004143","url":null,"abstract":"<p><strong>Background: </strong>Although previous evidence generally agreed on the short-term dual antiplatelet therapy (DAPT) for mild stroke or transient ischaemic attack (TIA), there is no consensus on the optimal threshold for stroke severity and initiation timing of DAPT. We conducted an updated meta-analysis of randomised controlled trials to evaluate early DAPT versus single therapy in mild stroke or TIA.</p><p><strong>Methods: </strong>We systematically reviewed double-blind and randomised controlled trials up to October 2024 evaluating DAPT versus monotherapy for acute mild, non-cardioembolic ischaemic stroke (National Institute of Health Stroke Scale; NIHSS≤5) or TIA within 72 hours of ictus. Random effects models generated risk ratio (RR) with 95% CIs for outcomes including stroke, composite vascular events, ischaemic stroke, major bleeding, haemorrhagic stroke and all-cause mortality.</p><p><strong>Results: </strong>Pooled data from five trials (n=27 559) demonstrated that DAPT versus monotherapy lowered the risk of stroke recurrence (RR, 0.77; 95% CI 0.70 to 0.83), composite vascular events (RR, 0.75; 95% CI 0.68 to 0.83) and ischaemic stroke (RR, 0.74; 95% CI 0.68 to 0.81). However, DAPT increased the risk of major bleeding (RR, 2.19; 95% CI 1.38 to 3.49) and haemorrhagic stroke (RR, 2.08; 95% CI 1.13 to 3.82), with no significant increase in the risk of all-cause mortality (RR, 1.28; 95% CI 0.95 to 1.71).</p><p><strong>Conclusions: </strong>For acute mild stroke (NIHSS ≤5) or patients with TIA within 72 hours of ictus, early DAPT initiation demonstrates net clinical benefit through reducing ischaemic events, despite an increase in bleeding complications, without affecting mortality.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of brain structural damage related to cerebral small vessel disease in general population with intracranial artery stenosis.","authors":"Zi-Ang Pan, Zi-Yue Liu, Xing-Qi Pan, Fei-Fei Zhai, Ding-Ding Zhang, Ming Yao, Li-Xin Zhou, Jun Ni, Zheng-Yu Jin, Shu-Yang Zhang, Li-Ying Cui, Fei Han, Yi-Cheng Zhu","doi":"10.1136/svn-2025-004471","DOIUrl":"https://doi.org/10.1136/svn-2025-004471","url":null,"abstract":"<p><strong>Background and aims: </strong>Covert MRI markers of cerebral small vessel disease (CSVD) can coexist with large artery atherosclerosis. We aimed to explore whether the spatial distributions of these markers were diverse in people with or without intracranial artery stenosis (ICAS).</p><p><strong>Methods: </strong>This cross-sectional analysis included 1206 stroke-free participants (aged 55.69±9.27, 62.94% female) with brain MRI and MR angiography from community-based Shunyi cohort. We analysed the relationships between ICAS and CSVD markers. We also compared the probability maps of lacunes, cerebral microbleeds (CMB), white matter hyperintensities (WMH) and cortex morphology at a voxel/vertex-wise level in groups with and without ICAS.</p><p><strong>Results: </strong>ICAS increased the risk of lacunes by 2.99-fold (95% CI 1.99 to 4.50, p<0.001), lacunes ≥3 by 5.32 times (95% CI 2.76 to 10.28, p<0.001), correlated with WMH volume (β=0.332, SE=0.059, p<0.001), WMH Fazekas scores ≥5 (OR 4.50, 95% CI 2.44 to 8.29, p<0.001) and brain parenchymal fraction (β=-0.012, SE=0.002, p<0.001), but not with CMB. ICAS is associated with lacunes in the corresponding blood supply area. Lacunes that coexist with ICAS were prone in basal ganglia, while the lacunes without ICAS appeared in centrum semiovale more often. WMH with ICAS was prone to present in deep white matter involving the bilateral pyramidal tracts and superior thalamic radiation. People with ICAS were susceptible to worse cortical atrophy of right superior frontal and left rostral anterior cingulate. No obvious distributional differences were found for CMB between the two groups.</p><p><strong>Conclusions: </strong>Since ICAS may be involved in the upstream pathogenesis of lacunes, white matter lesions and cortical atrophy, the impact of ICAS should not be ignored when evaluating MRI markers of CSVD.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BEST-BAO: a multicentre, prospective, randomised controlled trial of endovascular treatment with or without intravenous thrombolysis in acute ischaemic stroke due to basilar artery occlusion - study protocol and rationale.","authors":"Yang Xiang, Shu Yang, Lei Guo, Chongya Dong, Charles B L M Majoie, Adnan H Siddiqui, J Mocco, Fabiano Cavalcante, Bing-Hu Li, Jian-Hong Wang, Bin Huang, Duo-Zi Wang, Neng-Wei Yu, Wouter J Schonewille, Aquilla S Turk, Fu-Qiang Guo","doi":"10.1136/svn-2025-004144","DOIUrl":"https://doi.org/10.1136/svn-2025-004144","url":null,"abstract":"<p><strong>Background: </strong>Endovascular treatment (EVT) is safe and effective in treating acute ischaemic stroke due to basilar artery occlusion (AIS-BAO); nonetheless, the impact of intravenous thrombolysis (IVT) on its efficacy remains unclear.</p><p><strong>Objective: </strong>To compare the effectiveness and safety of EVT with or without prior IVT in treating AIS-BAO patients within 4.5 hours after stroke onset.</p><p><strong>Methods and design: </strong>A multicentre, prospective, randomised, open-label controlled clinical trial with blinded assessment of endpoints. 340 patients will be consecutively randomised to receive IVT plus EVT or direct EVT in a ratio of 1:1 from about 100 hospitals in China. An interim analysis is planned when one-third (114) of the patients have completed the primary endpoint follow-ups. It anticipates that IVT plus EVT demonstrates superiority over direct EVT. If the superiority of IVT plus EVT over direct EVT is less than expected, the sample size may be expanded by up to 20% of the original size. If the efficacy of the two groups is similar, it will shift to a non-inferiority hypothesis, aiming to evaluate whether direct EVT is non-inferior to IVT plus EVT.</p><p><strong>Outcome: </strong>The primary endpoint is the proportion of independent neurological function defined as a modified Rankin Scale score of 0 to 2 at 90±14 days after stroke onset.</p><p><strong>Discussion: </strong>This trial is expected to provide novel evidence of the superiority or non-inferiority between EVT with or without IVT in the treatment of patients with AIS-BAO.</p><p><strong>Trial registration: </strong>NCT05631847 at ClinicalTrials.gov and ChiCTR2300070584 at Chictr.org.cn.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain-targeted extracellular vesicles for anti-cuproptosis therapy in subarachnoid haemorrhage.","authors":"Pengcheng Xu, Jian Fang, Feiyun Qin, Dayong Xia, Jinlong Yuan, Bin Sheng, Niansheng Lai","doi":"10.1136/svn-2025-004248","DOIUrl":"https://doi.org/10.1136/svn-2025-004248","url":null,"abstract":"<p><strong>Background: </strong>Subarachnoid haemorrhage (SAH) is primarily caused by ruptured aneurysms with high mortality worldwide. Cuproptosis is a copper-induced cell death that regulates lipoylated tricarboxylic acid cycle proteins. The link between cuproptosis and SAH is unclear. To inhibit cuproptosis for SAH treatment, we designed brain-targeted delivery of siRNA to inhibit cuproptosis.</p><p><strong>Methods: </strong>Transcriptome data of SAH related to cuprotosis were extracted from the Gene Expression Omnibus and defined using quantitative reverse transcription-PCR. We injected RVG-RBCEVs/siRNA (rabies virus glycoprotein-red blood cell extracellular vesicles/siRNA) peripherally to deliver LIAS (lipoyl synthase) siRNA to the brain tissues of SAH mice. The influences of RVG-RBCEVs/siRNA on copper levels, enrichment of cuproptosis functional proteins, glutathione and malondialdehyde content, mitochondrial respiration and membrane potential, transmission electron microscope, a neurological score, brain water content, blood-brain barrier injury and Fluoro-Jade C staining were examined.</p><p><strong>Results: </strong>Our findings revealed that three cuproptosis-related genes (CRGs) were differentially expressed. The RVG peptides were conjugated to the red blood cell extracellular vesicle surface by bio-orthogonal click chemistry reactions, and then the loading of siRNA was conducted. RVG-RBCEVs/siRNA was selectively taken up by neurons but not glial cells; it facilitated the downregulation of LIAS of CRGs, reduced the accumulation of reactive oxygen species, inhibited neuronal cuprotosis and exerted neuroprotective effects in vivo.</p><p><strong>Conclusions: </strong>These findings suggest that cuprotosis is critical for inducing neural injury after SAH. Neuron-targeted RVG-RBCEVs/siRNA treatment attenuated oxidative stress by inhibiting cuproptosis via suppressed LIAS expression. This innovative approach alleviates neurobehavioural impairments and represents a neuroprotective strategy following SAH.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}