Journal of Investigative Medicine最新文献

{"title":"Antiplatelet therapy versus intravenous thrombolysis for mild acute ischaemic stroke: a living systematic review and meta-analysis.","authors":"Mingzhen Qin, Tingting Liu, Xinyi Shi, Luda Feng, Tingting Li, Zixin Cheng, Sisong Cheng, Congren Zhou, Mingrun Zou, Qi Jia, Chi Zhang, Ying Gao","doi":"10.1136/svn-2024-003097","DOIUrl":"10.1136/svn-2024-003097","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have shown contradictory results between early application of antiplatelet therapy and intravenous thrombolysis (IVT) for mild acute ischaemic stroke (AIS), with National Institutes of Health Stroke Scale score 0-5.</p><p><strong>Objective: </strong>To compare the benefits and risks of antiplatelet therapy and IVT in patients with mild AIS.</p><p><strong>Methods: </strong>A systematic search of MEDLINE, Embase and Cochrane Library was conducted from database inception until July 2023, without language restriction. Randomised clinical trials (RCTs) or observational studies were selected. The primary outcomes were 90-day functional outcomes, measured by the modified Rankin Scale (mRS) score. The protocol has been registered before data collection.</p><p><strong>Results: </strong>Two RCTs and four observational studies with relatively low risk of bias that enrolled 3975 patients were analysed (2454 in antiplatelet therapy and 1521 in IVT therapy). There were no significant differences between antiplatelet therapy and IVT in 90-day functional outcomes (mRS 0-1, OR 1.08 (95% CI 0.73 to 1.58); mRS 0-2, OR, 1.04 (95% CI 0.63 to 1.73)), death (OR, 0.64 (95% CI 0.19 to 2.13)) and stroke recurrence (OR, 0.71 (95% CI 0.28 to 1.79)). Antiplatelet therapy was associated with a reduced risk of symptomatic intracranial haemorrhage (sICH) compared with IVT (OR, 0.20 (95% CI 0.06 to 0.69)).</p><p><strong>Conclusions: </strong>Among patients with mild AIS, compared with IVT, early application of antiplatelet therapy was not significantly associated with improved functional outcomes, reduced death or stroke recurrence, but was significantly associated with a reduced risk of sICH.</p><p><strong>Prospero registration number: </strong>CRD42023447862.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972127","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":"Determinants of prehospital and in-hospital delay in patients with symptomatic carotid stenosis and their influence on the outcome after elective carotid endarterectomy.","authors":"Felix Kirchhoff, Christoph Knappich, Michael Kallmayer, Bianca Bohmann, Vanessa Lohe, Pavlos Tsantilas, Shamsun Naher, Hans-Henning Eckstein, Andreas Kühnl","doi":"10.1136/svn-2024-003098","DOIUrl":"10.1136/svn-2024-003098","url":null,"abstract":"<p><strong>Background: </strong>This study analyses the determinants of prehospital (index event to admission) and in-hospital delay (admission to carotid endarterectomy (CEA)). In addition, the analysis addresses the association between prehospital or in-hospital delay and outcomes after CEA for symptomatic patients in German hospitals.</p><p><strong>Materials and methods: </strong>This retrospective analysis is based on the nationwide German statutory quality assurance database. 55 437 patients were included in the analysis. Prehospital delay was grouped as follows: 180-15, 14-8, 7-3, 2-0 days or 'in-hospital index event'. In-hospital delay was divided into: 0-1, 2-3 and >3 days. The primary outcome event (POE) was in-hospital stroke or death. Univariate and multivariable regression analyses were performed for statistical analysis. The slope of the linear regression line is given as the β-value, and the rate parameter of the logistic regression is given as the adjusted OR (aOR).</p><p><strong>Results: </strong>Prehospital delay was 0-2 days in 34.9%, 3-14 days in 29.5% and >14 days in 18.6%. Higher age (β=-1.08, p<0.001) and a more severe index event (transitory ischaemic attack: β=-4.41, p<0.001; stroke: β=-6.05, p<0.001, Ref: amaurosis fugax) were determinants of shorter prehospital delay. Higher age (β=0.28, p<0.001) and female sex (β=0.09, p=0.014) were associated with a longer in-hospital delay. Index event after admission (aOR 1.23, 95% CI: 1.04 to 1.47) and an intermediate in-hospital delay of 2-3 days (aOR 1.15, 95% CI: 1.00 to 1.33) were associated with an increased POE risk.</p><p><strong>Conclusions: </strong>This study revealed that older age, higher American Society of Anesthesiology (ASA) stage, increasing severity of symptoms and ipsilateral moderate stenosis were associated with shorter prehospital delay. Non-specific symptoms were associated with a longer prehospital delay. Regarding in-hospital delay, older age, higher ASA stage, contralateral occlusion, preprocedural examination by a neurologist and admission on Fridays or Saturdays were associated with lagged treatment. A very short (<2 days) prehospital and intermediate in-hospital delay (2-3 days) were associated with increased risk of perioperative stroke or death.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538820","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":"Impact of premorbid hypertension and renin-angiotensin-aldosterone system inhibitors on the severity of aneurysmal subarachnoid haemorrhage: a multicentre study.","authors":"Ping Zhong, Zhiwen Lu, Zhangyu Li, Tianxiao Li, Qing Lan, Jianmin Liu, Sifang Chen, Zhanxiang Wang, Qinghai Huang","doi":"10.1136/svn-2023-003052","DOIUrl":"10.1136/svn-2023-003052","url":null,"abstract":"<p><strong>Background: </strong>Hypertension is widely acknowledged as a significant contributory factor to the heightened risk of intracranial aneurysm rupture. Nevertheless, the impact of hypertension management on the outcomes subsequent to aneurysmal subarachnoid haemorrhage (aSAH), particularly concerning the severity of aSAH, remains an underexplored area.</p><p><strong>Methods: </strong>We conducted a retrospective analysis using data from a prospectively multicentre cohort of 4545 patients with aSAH in China. Premorbid hypertension status and the utilisation of antihypertensive medications prior to admission were set as key exposure factors. The primary outcomes encompassed unfavourable clinical grading scales observed on admission. Employing multivariable logistic regression, we explored the association between premorbid hypertension status, preadmission use of renin-angiotensin-aldosterone system (RAAS) inhibitors and unfavourable clinical grading scales.</p><p><strong>Results: </strong>In comparison to patients with normal blood pressure, only uncontrolled hypertension demonstrated a significant and independent association with an elevated risk of poor outcomes on the Hunt-Hess scale (OR=1.799, 95% CI 1.413 to 2.291, p<0.001) and the World Federation of Neurological Surgeons (WFNS) scale (OR=1.721, 95% CI 1.425 to 2.079, p<0.001). Furthermore, the antecedent use of RAAS inhibitors before admission was markedly and independently linked to a diminished risk of adverse outcomes on the Hunt-Hess scale (OR=0.653, 95% CI 0.430 to 0.992, p=0.046) and the WFNS scale (OR=0.656, 95% CI 0.469 to 0.918, p=0.014).</p><p><strong>Conclusions: </strong>Uncontrolled hypertension markedly elevates the risk of adverse clinical outcomes following an aSAH. Conversely, the preadmission utilisation of RAAS inhibitors demonstrates a noteworthy association with a favourable clinical outcome after aSAH.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421502","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":"Association of <i>APOE</i> genotype with CT markers of cerebral amyloid angiopathy in spontaneous intracerebral haemorrhage.","authors":"Qiong Yang, Xiangzhu Zeng, Lu Tang, Xiaolu Liu, Kailin Xia, Feng Gao, Xu Huang, Nan Li, Dongsheng Fan","doi":"10.1136/svn-2024-003477","DOIUrl":"10.1136/svn-2024-003477","url":null,"abstract":"<p><strong>Background and objective: </strong>We investigated the association of <i>APOE</i> alleles with CT-based cerebral amyloid angiopathy (CAA) markers including subarachnoid extension (SAE) and finger-like projection (FLP).</p><p><strong>Methods: </strong>We included patients with acute primary supratentorial intracerebral haemorrhage (ICH) from a multicentre cohort in China. First, the association of <i>APOE</i> with ICH location (lobar vs non-lobar) was evaluated. Next, the relationships of <i>APOE</i> with SAE, FLP, and the coexistence of the two (SAE+FLP) were evaluated.</p><p><strong>Results: </strong>533 patients with supratentorial ICH were enrolled. Among them were 138 patients with lobar ICH and 395 with non-lobar ICH. Compared with the non-lobar group, <i>APOE</i> ε4 (OR 1.894, 95% CI 1.138 to 3.154, p=0.014) and ε2/ε4 (OR 6.098, 95% CI 1.414 to 26.293, p=0.015) were associated with lobar ICH. With regard to CAA markers, <i>APOE</i> ε2 was associated with SAE (OR 2.109, 95% CI 1.167 to 3.810, p=0.013), ε4 was associated with FLP and SAE+FLP (OR 3.026, 95% CI 1.353 to 6.767, p=0.007; OR 3.514, 95% CI 1.485 to 8.316, p=0.004, respectively) and ε2/ε4 was associated with all three factors (SAH: OR 7.599, 95% CI 1.764 to 32.734, p=0.006; FLP: OR 20.333, 95% CI 3.278 to 126.137, p=0.001; SAE+FLP: OR 30.568, 95% CI 4.460 to 209.503, p<0.001) after adjusting for age, and remained significant after adjusting for age and ICH volume.</p><p><strong>Conclusion: </strong>In patients with spontaneous supratentorial ICH, <i>APOE</i> ε2 and ε4 alleles were associated with SAE and FLP, respectively, suggesting <i>APOE</i> allele-specific effects on CT markers of CAA and their potential mechanisms.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796573","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":"Healthy lifestyles are associated with alleviating the single-nucleotide polymorphism-based genetic risks of ischaemic stroke, intracerebral haemorrhage and myocardial infarction.","authors":"Jingru Wang, Zhenqiu Liu, Chengxin Hu, Renjia Zhao, Dongliang Zhu, Yijing Xie, Pengyan Zhang, Mei Cui, Kelin Xu, Genming Zhao, Li Jin, Xingdong Chen, Chen Suo, Yanfeng Jiang","doi":"10.1136/svn-2024-003257","DOIUrl":"10.1136/svn-2024-003257","url":null,"abstract":"<p><strong>Background: </strong>Both genetic and lifestyle factors contribute to myocardial infarction (MI) and stroke, including ischaemic stroke (IS) and intracerebral haemorrhage (ICH). We explored how and the extent to which a healthy lifestyle, by considering a comprehensive list, could counteract the genetic risk of those diseases, respectively.</p><p><strong>Methods: </strong>315 044 participants free of stroke and MI at baseline were identified from the UK Biobank. Genetic risk scores (GRS) for those diseases were constructed separately and categorised as low, intermediate and high by tertile. Lifestyle risk scores (LRS) were constructed separately using smoking, alcohol intake, physical activity, dietary patterns and sleep patterns. Similarly, participants were categorised into low, intermediate and high LRS. The data were analysed using Cox proportional hazard models.</p><p><strong>Results: </strong>Over a median follow-up of 12.8 years, 4642, 1046 and 9485 participants developed IS, ICH and MI, respectively. Compared with participants with low levels of GRS and LRS, the HRs of those with high levels of GRS and LRS were 3.45 (95% CI 2.71 to 4.41), 2.32 (95% CI 1.40 to 3.85) and 4.89 (95% CI 4.16 to 5.75) for IS, ICH and MI, respectively. Moreover, among participants with high GRS, the standardised 14-year rates of IS events were 4.40% (95% CI 3.45% to 5.36%) among those with high LRS. In contrast, it is only 1.78% (95% CI 1.63% to 1.94%) among those with low LRS. Similarly for MI, the high LRS group had standardised rates of 8.60% (95% CI 7.38% to 9.81%), compared with 3.34% (95% CI 3.12% to 3.56%) in low LRS. Among the high genetic risk group of ICH, the rate is reduced by about half compared low LRS to high LRS, although the rate was low for both (0.36% (95% CI 0.31% to 0.42%) and 0.71% (95% CI 0.36% to 1.05%), respectively).</p><p><strong>Conclusion: </strong>Healthy lifestyles were substantially associated with a reduction in the risk of IS, ICH and MI and attenuated the genetic risk of IS, ICH and MI by at least half, respectively.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460176","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":"Obesity and brain volumes: mediation by cardiometabolic and inflammatory measures.","authors":"Qi Zhou, Wanlin Zhu, Xueli Cai, Jing Jing, Mengxing Wang, Suying Wang, Aoming Jin, Xia Meng, Tiemin Wei, Yongjun Wang, Yuesong Pan","doi":"10.1136/svn-2023-003045","DOIUrl":"10.1136/svn-2023-003045","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the relationship between overall obesity, central obesity and brain volumes, as well as to determine the extent to which cardiometabolic and inflammatory measures act as mediators in the association between body mass index (BMI), waist-hip ratio (WHR) and brain volumes.</p><p><strong>Methods: </strong>In the context of counterfactual framework, mediation analysis was used to explore the potential mediation in which cardiometabolic and inflammatory measures may mediate the relationship between BMI, WHR, and brain volumes.</p><p><strong>Results: </strong>Among 2413 community-dwelling participants, those with high BMI or WHR levels experienced an approximately brain ageing of 4 years. Especially, individuals with high WHR or BMI under the age of 65 exhibited white matter hyperintensity volume (WMHV) differences equivalent to around 5 years of ageing. Conversely, in the high-level WHR population over the age of 65, premature brain ageing in gray matter volume (GMV) exceeded 4.5 years. For GMV, more than 45% of the observed effect of WHR was mediated by glycaemic metabolism indicators. This proportion increases to 78.70% when blood pressure, triglyceride, leucocyte count, and neutrophil count are jointly considered with glycaemic metabolism indicators. Regarding WHR and BMI's association with WMHV, cardiometabolic and inflammatory indicators, along with high-density lipoprotein cholesterol, mediated 35.50% and 20.20% of the respective effects.</p><p><strong>Conclusions: </strong>Overall obesity and central obesity were associated with lower GMV and higher WMHV, a process that is partially mediated by the presence of cardiometabolic and inflammatory measures.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005608","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":"DRug-coated Balloon for Endovascular treatment of sYmptOmatic intracraNial stenotic Disease (DR. BEYOND): the protocol of a multicentre randomised trial.","authors":"Dapeng Mo, Xu Tong, Xiaoqing Li, Chuan Qin, Yuesong Pan, Sheng Guan, Zhongrong Miao","doi":"10.1136/svn-2024-003259","DOIUrl":"10.1136/svn-2024-003259","url":null,"abstract":"<p><strong>Background: </strong>Although endovascular stenting is considered an effective and safe therapeutic option for symptomatic intracranial atherosclerotic disease (sICAD), an elevated rate of restenosis remains an important issue for the conventional bare-metal stent (BMS). Recent evidence from observational studies suggests that applying drug-coated balloons (DCB) in sICAD may decrease restenosis occurrence. Additional large randomised studies are warranted to provide firmer evidence and to determine which patients would benefit most from DCB.</p><p><strong>Aim: </strong>To design a randomised trial to examine DCB angioplasty (Taijieweiye intracranial paclitaxel-coated balloon catheter) versus BMS stenting (Wingspan intracranial stent system) in patients with sICAD.</p><p><strong>Design: </strong>This is a multicentre, prospective, randomised, open-label, blinded end-point study to assess whether DCB angioplasty reduces the risk of restenosis compared with BMS stenting in sICAD patients with high-grade stenosis (≥70%-99%). Our goal is to randomly assign 198 eligible individuals at a 1:1 ratio to undergo DCB angioplasty (intervention group) or BMS stenting (control group).</p><p><strong>Outcome: </strong>The primary efficacy outcome is restenosis at 6 months post treatment, that is, >50% stenosis in or within 5 mm of the treated segment and >20% absolute luminal loss. The primary safety outcome is stroke or death within 30 days post treatment.</p><p><strong>Discussion: </strong>The DRug-coated Balloon for Endovascular treatment of sYmptOmatic intracraNial stenotic Disease trial aims to produce strong evidence on the efficacy and safety of DCB angioplasty as a promising therapeutic option for sICAD cases with high-grade stenosis.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753123","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":"New rat model of spinal cord infarction with long-lasting functional disabilities generated by intraspinal injection of endothelin-1.","authors":"Masayuki Otani, Yoshihiro Kushida, Yasumasa Kuroda, Shohei Wakao, Yo Oguma, Keisuke Sasaki, Shintaro Katahira, Ryohei Terai, Rie Ryoke, Hiroi Nonaka, Ryuta Kawashima, Yoshikatsu Saiki, Mari Dezawa","doi":"10.1136/svn-2023-002962","DOIUrl":"10.1136/svn-2023-002962","url":null,"abstract":"<p><strong>Background: </strong>The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days.</p><p><strong>Objective: </strong>We aimed to establish a rat model characterised by long-term survival and enduring SC dysfunction by inducing selective ischaemic SC damage.</p><p><strong>Methods: </strong>In 8-week-old male Wistar rats, a convection-enhanced delivery technique was applied to selectively deliver endothelin-1 (ET-1) to the anterior horn of the SC at the Th13 level, leading to SC infarction. The Basso, Beattie and Bresnahan (BBB) locomotor score was assessed for 56 days. The SC was examined by a laser tissue blood flowmeter, MRI, immunohistochemistry, triphenyl tetrazolium chloride (TTC) staining, Western blots and TUNEL staining.</p><p><strong>Results: </strong>The puncture method was used to bilaterally inject 0.7 µL ET-1 (2.5 mg/mL) from the lateral SC into the anterior horns (40° angle, 1.5 mm depth) near the posterior root origin. Animals survived until day 56 and the BBB score was stably maintained (5.5±1.0 at day 14 and 6.2±1.0 at day 56). Rats with BBB scores ≤1 on day 1 showed stable scores of 5-6 after day 14 until day 56 while rats with BBB scores >1 on day 1 exhibited only minor dysfunction with BBB scores >12 after day 14. TTC staining, immunostaining and TUNEL staining revealed selective ischaemia and neuronal cell death in the anterior horn. T2-weighted MR images showed increasing signal intensity at the SC infarction site over time. Western blots revealed apoptosis and subsequent inflammation in SC tissue after ET-1 administration.</p><p><strong>Conclusions: </strong>Selective delivery of ET-1 into the SC allows for more precise localisation of the infarcted area at the targeted site and generates a rat SC infarction model with stable neurological dysfunction lasting 56 days.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437622","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":"PRCP is a promising drug target for intracranial aneurysm rupture supported via multi-omics analysis.","authors":"Jinghao Wu, Yunyun Mei, XinYu Li, Wen-Kai Yu, Zi Han Zhou, Yinghao Yang, Pengpeng Niu, Yunchao Wang, Chang-He Shi, Hanghang Zhu, Wenjun He, Yuan Gao, Yuming Xu, Yusheng Li","doi":"10.1136/svn-2023-003076","DOIUrl":"10.1136/svn-2023-003076","url":null,"abstract":"<p><strong>Background: </strong>Cerebral aneurysms are life-threatening cerebrovascular disorders. Currently, there are no effective treatments for preventing disease progression. Mendelian randomisation (MR) is widely used to repurify licensed drugs and identify new therapeutic targets. Therefore, this study aims to investigate effective drug targets for preventing the formation and rupture of cerebral aneurysms and analyse their potential mechanisms.</p><p><strong>Methods: </strong>We performed a comprehensive study integrating two-sample MR analysis, colocalisation analysis and summary data-based Mendelian randomisation (SMR) to assess the causal effects of blood and brain druggable cis-expression quantitative trait loci (cis-eQTLs) on intracranial aneurysm (IA), unruptured intracranial aneurysm (UIA) and subarachnoid haemorrhage of IA rupture (SAH). Druggable genes were obtained from the study by Chris Finan <i>et al</i>, cis-eQTLs from the eQTLGen and PsychENCODE consortia. Results were validated using proteomic and transcriptomic data. Single-gene functional analyses probed potential mechanisms, culminating in the construction of a drug-gene regulation network.</p><p><strong>Results: </strong>Through the MR analysis, we identified four potential drug targets in the blood, including prolylcarboxypeptidase (PRCP), proteasome 20S subunit alpha 4 (PSMA4), LTBP4 and GPR160 for SAH. Furthermore, two potential drug targets (PSMA4 and SLC22A4) were identified for IA and one potential drug target (KL) for UIA after accounting for multiple testing (P(inverse-variance weighted)<8.28e-6). Strong evidence of colocalisation and SMR analysis confirmed the relevance of PSMA4 and PRCP in outcomes. Elevated PRCP circulating proteins correlated with a lower SAH risk. PRCP gene expression was significantly downregulated in the disease cohort.</p><p><strong>Conclusions: </strong>This study supports that elevated PRCP gene expression in blood is causally associated with the decreased risk of IA rupture. Conversely, increased PSMA4 expression in the blood is causally related to an increased risk of IA rupture and formation.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056959","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":"Why non-human primates are needed in stroke preclinical research.","authors":"Xiya Long, Jinsheng Zeng","doi":"10.1136/svn-2024-003504","DOIUrl":"10.1136/svn-2024-003504","url":null,"abstract":"<p><p>Numerous seemingly promising cerebroprotectants previously validated in rodents almost all have failed in stroke clinical trials. The failure of clinical translation strikes an essential need to employ more ideal animal models in stroke research. Compared with the most commonly used rodent models of stroke, non-human primates (NHPs) are far more comparable to humans regarding brain anatomy, functionality and pathological features. The aim of this perspective was to summarise the advantages of NHPs stroke models over rodents, discuss the current limitations of NHPs models, and cast an outlook on the future development of NHPs in stroke preclinical research.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113762","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}