Journal of Investigative Medicine最新文献

{"title":"Peripheral blood <i>GATA2</i> expression impacts <i>RNF213</i> mutation penetrance and clinical severity in moyamoya disease.","authors":"Yohei Mineharu, Takahiko Kamata, Mei Tomoto, Noriaki Sato, Yoshinori Tamada, Takeshi Funaki, Yuki Oichi, Kouji H Harada, Akio Koizumi, Tetsuaki Kimura, Ituro Inoue, Yasushi Okuno, Susumu Miyamoto, Yoshiki Arakawa","doi":"10.1136/svn-2024-003970","DOIUrl":"https://doi.org/10.1136/svn-2024-003970","url":null,"abstract":"<p><strong>Background: </strong>The p.R4810K founder mutation in the <i>RNF213</i> gene confers susceptibility to moyamoya disease (MMD) and non-MMD intracranial artery disease. However, penetrance is incomplete, and the underlying molecular mechanism remains unknown.</p><p><strong>Methods and results: </strong>Transcriptome analysis of peripheral blood was conducted with nine MMD patients and five unaffected mutation carriers from four familial MMD pedigrees. Bayesian network analysis identified upregulated gene modules associated with lipid metabolism and leucocyte development (including <i>GATA2</i> and <i>SLC45A3</i>), and epidermal growth factor receptor (EGFR) signalling (<i>UBTD1</i>). It also identified downregulated gene modules related to mitochondrial ribosomal proteins (<i>RPS3A</i> and <i>RPL26</i>), and cytotoxic T cell immunity (<i>GZMA</i> and <i>TRGC1</i>). The <i>GATA2</i> network was replicated through weighted gene co-expression network analysis and further examined in a case-control study, comprising 43 MMD patients, 16 non-MMD patients, 19 unaffected carriers and 35 healthy controls. <i>GATA2</i> exhibited a significant linear correlation with <i>SLC45A3</i> and was significantly higher in MMD patients compared with age-matched and sex-matched unaffected carriers or wild-type controls. Among patients with the p.R4810K mutation, higher <i>GATA2</i> expression was associated with an earlier age of onset, bilateral involvement and symptomatic disease onset.</p><p><strong>Conclusions: </strong>Peripheral blood <i>GATA2</i> expression was associated with increased penetrance of the <i>RNF213</i> mutation and more severe clinical manifestations in MMD.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056365","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":"Efficacy of immediate anti-hypertensive treatment in patients with acute ischaemic stroke stratified by mean arterial pressure and pulse pressure: a secondary analysis of the China Antihypertensive Trial in Acute Ischemic Stroke trial.","authors":"Ming Wang, Shiguang Zhu, Jiayi Long, Mengyue Cao, Yanbo Peng, Jing Chen, Tan Xu, Jiang He, Yonghong Zhang, Chongke Zhong","doi":"10.1136/svn-2024-003896","DOIUrl":"https://doi.org/10.1136/svn-2024-003896","url":null,"abstract":"<p><strong>Background: </strong>Whether mean arterial pressure (MAP) and pulse pressure (PP), two indicators of cerebral perfusion, could guide the selection of anti-hypertensive strategies after acute ischaemic stroke remains uncertain. Our study was to explore the impact of early anti-hypertensive intervention on adverse clinical outcomes following ischaemic stroke stratified by the levels of MAP and PP based on the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS).</p><p><strong>Methods: </strong>The trial randomised 4071 acute ischaemic stroke patients with elevated systolic blood pressure (SBP) to receive anti-hypertensive treatment (targeting a 10%-25% reduction in SBP during the 24 hours postrandomisation, reaching a BP level <140/90 mm Hg in 7 days, further keeping these levels throughout hospitalisation) or discontinue anti-hypertensive treatment during hospitalisation. The primary outcome was death or major disability at 14 days or hospital discharge. Study outcomes were analysed by comparing the BP-lowering intervention group and control group, stratified by tertiles of MAP or PP levels.</p><p><strong>Results: </strong>No significant difference was observed in the primary outcome between the intervention and control groups across all MAP (p=0.69 for homogeneity) and PP (p=0.78 for homogeneity) categories. The corresponding odds ratios (95% CIs) were 1.08 (0.85-1.36), 0.92 (0.74-1.15) and 1.00 (0.81-1.25) for participants with low, intermediate, and high MAP and were 0.99 (0.79-1.25), 1.06 (0.84-1.34) and 0.95 (0.77-1.18) for participants in PP subgroups, respectively. Furthermore, early anti-hypertensive intervention was not associated with secondary outcomes (including neurological deterioration, recurrent stroke, vascular events and all-cause mortality) by MAP and PP (all p>0.05).</p><p><strong>Conclusions: </strong>Early anti-hypertensive therapy neither decreased nor increased the odds of major disability, mortality, recurrent stroke or vascular events in patients with acute ischaemic stroke regardless of different MAP and PP levels.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov identifier: NCT01840072.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021521","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 socioeconomic deprivation on mechanical thrombectomy outcomes after acute ischaemic stroke: findings from a London-based multicentre study.","authors":"Lucio D'Anna, Soma Banerjee, Viva Levee, Katherine Chulack, Fahad Sheikh, Feras Fayez, Tsering Dolkar, Nina Mansoor, Matthew Fallon, Adelaida Gartner, Robert Simister, Liqun Zhang","doi":"10.1136/svn-2024-003915","DOIUrl":"https://doi.org/10.1136/svn-2024-003915","url":null,"abstract":"<p><strong>Background: </strong>Mechanical thrombectomy (MT) improves outcomes in patients who had an acute ischaemic stroke due to large vessel occlusion (LVO). However, socioeconomic status (SES) can influence recovery and prognosis. This study investigated the effect of SES, assessed via the Index of Multiple Deprivation (IMD), on MT outcomes in a multicentre London cohort.</p><p><strong>Methods: </strong>This retrospective study included patients with anterior circulation LVO treated with MT between 2021 and 2023 at three London hospitals. Patients were grouped into IMD_1-5 (more deprived) and IMD_6-10 (less deprived). Inverse probability weighting balanced baseline characteristics. Primary outcomes were 90-day functional independence (modified Rankin Scale (mRS) 0-2) and 90-day mRS shift. Secondary outcomes included recanalisation, early neurological changes, 90-day mortality, symptomatic intracerebral haemorrhage (sICH) and haemorrhagic transformation (HT). Subgroup analyses explored interactions between IMD and demographic or clinical factors. LASSO (Least Absolute Shrinkage and Selection Operator) regression identified predictors of functional independence, while receiver operating characteristic analysis evaluated IMD's predictive value.</p><p><strong>Results: </strong>Among 1219 patients with acute LVO ischemic stroke treated with MT, 533 (43.7%) were in IMD_1-5 and 686 (56.3%) in IMD_6-10. IMD_1-5 patients had lower odds of functional independence at 90 days (RR 0.79, 95% CI 0.70 to 0.90) and worse mRS shift (OR 1.29, 95% CI 1.06 to 1.58). They also had higher risks of sICH (RR 2.07, 95% CI 1.54 to 2.67) and HT (Risk Ratio 1.47, 95% CI 1.21 to 1.80). Subgroup analysis highlighted IMD's predictive importance in Asian or mixed ethnicity groups. A model incorporating IMD, age, sex, hypertension and National Institutes of Health Stroke Scale (area under the curve 0.656) demonstrated predictive accuracy for 90-day functional independence.</p><p><strong>Conclusions: </strong>Lower SES correlates with worse outcomes and higher complications post-MT, even within a universal healthcare system. Addressing SES disparities could improve stroke care equity.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035245","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":"Intracerebral haemorrhage laterality and associations with mood and pain: a MISTIE III substudy.","authors":"Dawson C Cooper, Efrat Abramson, Wendy C Ziai, Matthew L Flaherty, Vishank A Shah, Radhika Avadhani, Noeleen Ostapkovich, Lourdes Carhuapoma, Issam Awad, Mario Zuccarello, Daniel Hanley, Lauren H Sansing","doi":"10.1136/svn-2024-003755","DOIUrl":"https://doi.org/10.1136/svn-2024-003755","url":null,"abstract":"<p><strong>Background: </strong>The prognostic significance of the affected hemisphere in haemorrhagic stroke remains uncertain. We aimed to determine the relationship between the affected hemisphere (right or left) and differences in non-motor outcomes, including mood and pain, in patients with acute, supratentorial intracerebral haemorrhage (ICH). These non-motor outcomes are often overlooked in studies following ICH but impact patient recovery and well-being.</p><p><strong>Methods: </strong>A secondary prespecified analysis of the Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation (MISTIE) III study-a randomised, international, multicentre, placebo-controlled trial of participants with spontaneous, non-traumatic, supratentorial ICH of 30 mL or more that evaluated minimally invasive surgery with thrombolysis compared with standard medical care. Outcomes included EQ-5D three-level version (EQ-5D-3L, composite and individual non-motor components) and modified Rankin scale (mRS) scores at days 30, 180 and 365 post-ICH.</p><p><strong>Results: </strong>A total of 493 participants were eligible for analysis at day 30 following ICH. In multivariable analyses, patients with right hemispheric ICH were more likely to report problems with pain and discomfort at days 30 (β=0.257 (95% CI 0.131, 0.383)), 180 (β=0.213 (95% CI 0.090, 0.336)) and 365 (β=0.209 (95% CI 0.090, 0.328)) post-ICH. Patients with right hemispheric ICH were also more likely to report problems with anxiety and depression at days 30 (β=0.160 (95% CI 0.030, 0.291)) and 180 (β=0.171 (95% CI 0.049, 0.293)) following ICH. There were no differences in mRS scores between patients with left or right-sided haemorrhages.</p><p><strong>Conclusions: </strong>Right hemispheric lesions were associated with increased reports of mood-related symptoms (depression, anxiety) and pain in patients with acute ICH over time.</p><p><strong>Trial registration number: </strong>NCT01827046.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035768","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":"Effect of intravenous alteplase before endovascular therapy for atherothrombotic stroke-related large vessel occlusion: subanalysis of the RESCUE AT-LVO registry.","authors":"Hirotaka Hayashi, Satoshi Namitome, Seigo Shindo, Shinichi Yoshimura, Manabu Shirakawa, Mikiya Beppu, Nobuyuki Sakai, Hiroshi Yamagami, Kazutaka Uchida, Kazunori Toyoda, Yuji Matsumaru, Yasushi Matsumoto, Kenichi Todo, Mikito Hayakawa, Shinzo Ota, Masafumi Morimoto, Masataka Takeuchi, Hirotoshi Imamura, Hiroyuki Ikeda, Kanta Tanaka, Hideyuki Ishihara, Hiroto Kakita, Takanori Sano, Hayato Araki, Tatsufumi Nomura, Fumihiro Sakakibara, Mitsuharu Ueda, Makoto Nakajima","doi":"10.1136/svn-2024-003983","DOIUrl":"https://doi.org/10.1136/svn-2024-003983","url":null,"abstract":"<p><strong>Background: </strong>Whether intravenous thrombolysis (IVT) should be administered prior to endovascular therapy (EVT) in patients with atherothrombotic stroke-related large vessel occlusion (AT-LVO) remains unclear. This study aimed to assess the efficacy and safety of IVT administered before EVT in this patient population.</p><p><strong>Methods: </strong>We analysed the data from a multicentre registry of patients who underwent EVT for AT-LVO. Patients were categorised based on presumed mechanism of occlusion: in situ occlusion (intracranial group) or embolism from cervical artery occlusion/stenosis (tandem group). We compared the efficacy and safety of IVT before EVT in patients who received IVT (IVT stratum) and those who did not (non-IVT stratum). The primary outcome was a modified Rankin Scale score of 0-2 at 90 days.</p><p><strong>Results: </strong>Among the 336 patients in the intracranial group, 99 patients underwent IVT. The rate of favourable functional outcomes did not differ between IVT and non-IVT strata (51.1% vs 47.6%; adjusted ORs (aORs) (95% CI), 1.18 (0.66 to 2.09)); whereas any intracranial haemorrhage (ICH) (10.1% vs 3.8%; aOR, 2.98 (1.01 to 9.26)) and mortality at 90 days (6.4% vs 1.3%; aOR, 4.66 (1.02 to 26.73)) were significantly higher in the IVT stratum. Among the 233 patients in the tandem group, 88 patients underwent IVT, with no significant differences in efficacy or safety outcomes between the strata.</p><p><strong>Conclusion: </strong>In patients with AT-LVO, IVT before EVT did not improve outcomes and was associated with increased risk of ICH and mortality in those with in situ intracranial occlusion. IVT before EVT may not be recommended in patients with atherosclerotic intracranial occlusions.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039754","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":"Functional outcomes of minimally invasive surgery treatment for patients with small supratentorial spontaneous intracerebral haematoma less than 30 mL: a propensity score matching study.","authors":"Hanyu Sun, Xinqun Luo, Zhang Guo, Lingyun Zhuo, Dekui Cheng, Zhuyu Gao, Qiu He, Zheng Yan, Dezhi Kang, Wenhua Fang, Fuxin Lin","doi":"10.1136/svn-2024-003893","DOIUrl":"https://doi.org/10.1136/svn-2024-003893","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the efficacy of frameless robot-assisted stereotactic aspiration coupled with catheter thrombolysis (SA-CT) in treating supratentorial spontaneous intracerebral haemorrhage (sICH) with small haematoma volumes (<30 mL).</p><p><strong>Methods: </strong>We analysed the clinical and long-term outcome data for patients who had haematoma volumes <30 mL and underwent SA-CT between August 2019 and June 2023. Then, we matched the patients receiving conservative treatment during the same period from a multicentre intracerebral haemorrhage database using propensity score matching. The outcomes included the restoration of independent standing ability and mortality within 1 year after onset.</p><p><strong>Results: </strong>340 patients were included in the final analysis. A greater proportion of patients in the surgery group regained the ability to stand independently within 1 year (89.1% vs 78.1%, p=0.049). The Kaplan-Meier curve showed that the cumulative standing rate in the surgery group was higher than that in the conservative group (90.4% vs 82.0%, p=0.007) within 1 year, and the median time to regain standing was shorter in the surgery group (30 days vs 34 days). The mortality rates were lower in the surgery group (p<0.05). Multivariate Cox regression analysis revealed that frameless robot-guided SA-CT (adjusted HR 1.80; 95% CI 1.37 to 2.38; p<0.001), age, haematoma volume, the severe Glasgow Coma Scale scores and pneumonia were independent factors associated with standing recovery within 1 year after onset.</p><p><strong>Conclusions: </strong>Frameless robot-guided SA-CT for small supratentorial haematoma with contralateral hemiplegia seems safe and potentially facilitates the recovery of independent standing ability and reduces the mortality rates.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033077","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":"E<b>F</b>fects of Y-6 S<b>U</b>blingual Tablets for Pa<b>T</b>ients with Ac<b>U</b>te Ischemic St<b>R</b>ok<b>E</b> (FUTURE): a phase II, randomised, double-blind, double-dummy, placebo-controlled, parallel trial.","authors":"Yicong Wang, Baoshan Qiu, Ling Guan, Hui Qu, Yuesong Pan, Xiaochuan Huo, Liping Liu, Zhongrong Miao, Shuya Li, Zixiao Li, Xingquan Zhao, Yongjun Wang, Lei Wang, Xiaoling Liao, Yilong Wang","doi":"10.1136/svn-2024-003666","DOIUrl":"https://doi.org/10.1136/svn-2024-003666","url":null,"abstract":"<p><strong>Background: </strong>Acute ischaemic stroke, due to its high mortality and disability rates, imposes a significant economic and social burden worldwide. Typically, endovascular treatment within the therapeutic window is provided to salvage the ischaemic penumbra; however, even when recanalisation is successful during endovascular treatment, the clinical outcomes may still be disappointing. This highlights the necessity of further research, so as to discover better solutions to futile recanalisation and improve patient outcomes.</p><p><strong>Objective: </strong>To investigate the efficacy and safety of Y-6 sublingual tablets (cilostazol and dexborneol) compared with a placebo in the treatment of patients with acute ischaemic stroke caused by large vessel occlusion.</p><p><strong>Method: </strong>The efficacy and safety of Y-6 sublingual tablets in patients with acute ischaemic stroke are evaluated in a phase II, randomised, double-blind, double-dummy, placebo-controlled, parallel clinical trial. Eligible patients having provided informed consent are randomised into five groups for a 28-day treatment period. The primary outcome is the percentage of patients achieving the modified Rankin Scale score of 0-1 at 90 days.</p><p><strong>Discussion: </strong>The EFfects of Y-6 SUblingual Tablets for PaTients with AcUte Ischemic StRokE trial assesses whether Y-6 sublingual tablets are effective and safe in improving the clinical outcomes of patients with acute ischaemic stroke caused by large vessel occlusion.</p><p><strong>Trial registration number: </strong>NCT06138834.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020304","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":"Quantitative histopathological analysis of thrombi retrieved by mechanical thrombectomy and their association with stroke aetiology.","authors":"Zhiyi Jiang, Juan Huang, Shuntong Hu, Ruping Xiang, Longfeng Ran, Yiwei Chen, Dujie Xie, Panyao Long, Xiaobo Li, Yi Yuan","doi":"10.1136/svn-2024-003543","DOIUrl":"10.1136/svn-2024-003543","url":null,"abstract":"<p><strong>Background and purpose: </strong>Approximately 25% of acute large vessel occlusive (LVO) ischaemic strokes are of unknown thrombotic origin, and there is a need to establish the aetiology to guide subsequent preventative measures. The aim of this study was to quantify thrombus composition in patients with LVO and explore associations between thrombus composition and stroke aetiology.</p><p><strong>Methods: </strong>Thrombi were extracted from 132 patients with acute ischaemic stroke. Erythrocytes, leucocytes and F+P (fibrin+platelet) proportions were assessed in tissue sections stained with H&E, while CD3⁺ T cells and neutrophil extracellular traps (NETs) were quantified in immunohistochemistry-stained sections. Thrombus components, clinical parameters and interventional variables were compared between different stroke subtypes defined by Trial of ORG 10172 in Acute Stroke Treatment criteria.</p><p><strong>Results: </strong>F+P composition was significantly higher (p<0.001) and erythrocyte proportions were significantly lower (p<0.001) in cardioembolic thrombi than in large artery atherosclerosis thrombi. The composition of thrombi from undetermined aetiology strokes resembled that from cardioembolic strokes. CD3⁺ T cell and NET proportions were not significantly different between stroke subtypes. CD3⁺ density per unit area was associated with the occlusive site, being significantly higher in the anterior circulation than the posterior circulation (p=0.004). Cardioembolic strokes were more common in the anterior circulation than large artery atherosclerosis strokes (p=0.002). Recanalisation time was significantly longer for large artery atherosclerosis emboli than for cardioembolic emboli (p=0.032).</p><p><strong>Conclusion: </strong>There is significant heterogeneity in thrombus composition among different stroke subtypes. The quantitative assessment of thrombus composition may be a useful biomarker of stroke aetiology, and strokes of undetermined aetiology may be more likely to have a cardioembolic origin.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659526","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 regulation of Atf3 and Lonp1 as therapeutic targets in cerebral ischaemia-reperfusion injury.","authors":"Weijian Fan, Min Zhou, Lin Zhou, Jindong Tong, Jinyun Tan, Weihao Shi, Bo Yu","doi":"10.1136/svn-2024-003324","DOIUrl":"10.1136/svn-2024-003324","url":null,"abstract":"<p><strong>Background: </strong>Cerebral ischemia-reperfusion injury (CIRI) leads to cognitive dysfunction, neuronal death, and inflammation. Understanding the molecular mechanisms underlying CIRI is crucial for developing effective therapeutic strategies.</p><p><strong>Objective: </strong>This study aims to investigate the roles of activating transcription factor 3 (Atf3) and lon protease homolog 1 (Lonp1) in CIRI, particularly focusing on how Atf3 regulates Lonp1 expression and its effects on mitochondrial function.</p><p><strong>Methods: </strong>Single-cell transcriptomics and proteomic analyses were employed to explore Atf3's influence on Lonp1 and its subsequent impact on neuronal survival and apoptosis.</p><p><strong>Results: </strong>The findings indicate that Atf3 plays a crucial role in modulating Lonp1 expression, which in turn affects mitochondrial function, neuronal survival, and apoptotic pathways.</p><p><strong>Conclusion: </strong>This study provides new insights into the regulatory mechanisms of Atf3 and Lonp1 in CIRI, identifying potential therapeutic targets for managing ischemic brain injury and neurodegenerative diseases.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568649","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":"Young stroke in Bangladesh: addressing rare cases with diagnostic challenges and much-needed solutions.","authors":"Manisha Das, Md Jubayer Hossain","doi":"10.1136/svn-2025-004178","DOIUrl":"https://doi.org/10.1136/svn-2025-004178","url":null,"abstract":"<p><p>Stroke is a leading cause of mortality and morbidity in Bangladesh, and young adults are increasingly affected. Common risk factors include hypertension, diabetes, dyslipidaemia, obesity and smoking, whereas rare causes include haematologic disorders, premature atherosclerosis, vasculopathy and arteritis. Treatment barriers include inadequate infrastructure, a lack of trained staff and high intervention costs. Bangladesh faces a scarcity of neurologists and well-equipped hospitals, necessitating strategies to mitigate the burden of stroke among young people. This editorial summarises the current knowledge regarding the aetiology, pathophysiology and challenges in diagnosing and treating stroke in young people in Bangladesh, while addressing rare vasculopathy. Initiatives to support young stroke survivors and their families were also discussed. Prospective cohort studies, such as the Norwegian Stroke in the Young Study, provide insights into optimising prevention and early intervention by assessing family history and subclinical vascular diseases, which have also been highlighted. Recommendations include advanced neuroimaging for risk assessment, incorporating patient care and rehabilitation into medical education, conducting relevant research and promoting healthy lifestyles through campaigns and training of the healthcare staff.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803330","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}