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Autoimmunity in acute ischemic stroke and the role of bloodbrain barrier: the dark side or the light one?

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Frontiers of Medicine 2019年第4期13卷 420-426页

作者： Nikolay V. Tsygan Alexandr P. Trashkov Igor V. Litvinenko Viktoriya A. Yakovleva Alexandr V. Ryabtsev Andrey G. Vasiliev Leonid P. churilov Department of Molecular and Radiation Biophysics B.P. Konstantinov Petersburg Nuclear Physics Institute Gatchina Leningrad Region 188300 Russian Federation Department of Nervous Diseases S.M. Kirov Military Medical Academy Saint Petersburg 194044 Russian Federation Department of Experimental Pharmacology I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry Saint Petersburg 194223 Russian Federation Department of Pathological Physiology with the Course of Immunopathology Saint Petersburg State Pediatric Medical University Saint Petersburg Russian Federation Department of Pathology Laboratory of the Mosaic of Autoimmunity Saint Petersburg State University Saint Petersburg 199034 Russian Federation

This article presents a synopsis of the current data on the mechanisms of blood-brain barrier (BBB) alteration and autoimmune response in acute ischemic stroke. Most researchers confirm the relationship between the severity of immunobiochemical changes and clinical outcome of acute ischemic stroke. Ischemic stroke is accompanied by aseptic inflammation, which alters the brain tissue and exposes the co-stimulatory molecules of the immune system and the neuronal antigens. To date, BBB is not considered the border between the immune system and central nervous system, and the local immune subsystems are found within and behind the BBB. BBB disruption contributes to the leakage of brain autoantigens and induction of secondary autoimmune response to neuronal antigens and long-term inflammation. Glymphatic system function is altered and jeopardized both in hemorrhagic and ischemic stroke types. The receptors of innate immunity (toll-like receptor-2 and toll-like receptor-4) are also involved in acute ischemia-reperfusion injury. Immune response is related to the key processes of blood clotting and fibrinolysis. At the same time, the stroke-induced immune activation may promote reparation phenomena in the brain. Subsequent research on the reduction of the acute ischemic brain injury through the target regulation of the immune response is promising.

关键词： stroke blood-brain barrier autoimmunity innate immunity inflammation cell death

Pathophysiology transforms into systemic pathobiology being an introductive course of translational medicine

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中国病理生理杂志 2013年第10期29卷 1877-1877页

作者： Leonid P.churilov Department of Pathology School of MedicineSt. Petersburg State University

Pathophysiology,as a science and curriculum discipline,stands in front of the biggest challenge of its *** extended far beyond the limits of its historical name and embedded aspects of pathochemistry,immunopathology,pathobiophysics and pathoinformatics,intermingling with translational *** and learning of pathophysiology should be modernized in accordance with the needs of nowadays,under the bias of its integrative role for medicine,analogous to that of systems biology among non-medical life *** pathophysiology grew into clinics(via laboratory and functional diagnostic tests,which are controlled clinical experiments).Thus,physicians of functional diagnosis,clinical immunology and biochemistry services,are in fact close to *** diagnostician has to compose a conceptual model of disease in order to explain and combine data for comprehension of a ***,such modeling is inherent to pathophysiology;hence competence of diagnostician is based on *** approach to patient,disease and education is traditional for Russian *** our department,classical lab experiments are joint to early start of Clinical Pathology(5th term),combined to case history analysis and lectures co-delivered by pathophysiologist and clinician with patient *** our teaching posters,pathophysiological,pathomorphological,clinical and historical data are *** net of digital television microscopes gives instant video archive of experimental results added to student's protocols of lab ***,we collected considerable experience in interdisciplinary project-oriented learning and interpret the role of modern pathophysiology as bridging scientific and clinical modes of reasoning and establishing common thesaurus for multiplying branches of medicine.

关键词：病理生理学系统生物学学科课程医学转化全身性实验室实验诊断测试

Pathophysiology transforms to pathobiology:new technologies and interdisciplinary project-oriented learning

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中国病理生理杂志 2009年第11期25卷 2248-2248页

作者： Leonid P. churilov Yury I. Stroev Vladimir J. Utekhin Department ofPathology School ofMedicine State University off.113 bld821st line V.O. St.Petersburg199106 Russia

Integrative role of pathophysiology in medicine is analogous to that of systemic biology among non-medical life sciences. Pathology rooted in morphology,because autopsy and microscopy in early 19th century revealed some loci and elements of disease. However,this was not enough for comprehension of systemic disorders and relations between elements. This promoted the involvement of physiology and birth of pathophysiology. For a long time the methodological options for bedside studies were scarce,so generations of physicians percepted pathophysiology as a science of lab and vivarium only,unlike pathomorphology,had integrated in clinics earlier. This lead to fornication between two sister branches of pathology and teaching of pathology and clinical subjects separated. Methodological progress of 20th century created basis for less or non-invasive patient studies. Current advances of pathochemistry,medical genetics,immunopathology,bioinformatics-give the chance to pathophysiology and pathomorphology spread far beyond the constraint of their historical names and intermingle. Current Pathophysiology grew into clinics (via laboratory and functional diagnosis,which contains clinical experimenting). This promotes re-integration of pathology sister branches,not via absorption,but through mutual shift to clinical correlations. Holistic approach to patient,disease and education is traditional for Russian medicine. In our pathophysiology teaching,classical lab experiments are joint to early start of clinical pathology (6th term),case history analysis,lectures co-delivered by pathologist and clinician with demonstration of patients. Pathomorphologist and clinician are included in state board for pathophysiology exam. In teaching posters pathophysiological,clinical and pathomorphological data are fused. Local net of digital television microscopes gives instant video archive of experimental results added to student's protocols of lab studies. Teaching posters and course papers are co

关键词：病理生理学病原生物学跨学科学习导向项目技术病理生理作用

Cuprum and Cobalt Nano-Particles Influence on Bull-Calves＇ Growth and Development

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材料科学与工程（中英文B版） 2013年第6期3卷 379-385页

作者： Gennady Ivanovich churilov Svetlana Dmitrievna Polishchuk Anna Anatolievna Nazarova State Medical University Ryazan 390026 Russia State Agrotechnological University Ryazan 390044 Russia

They have conducted the research to identify the possibility of increasing the abiotic polymerization intensity and efficiency both in the organism and in animals" muscular tissue. These tasks can be partially solved in a case of biogenous nano-metals usage such as cuprum and cobalt when adding them to the fodder. To estimate the meat productivity indexes they have formed black and white bull-calves groups. The nano-crystal cobalt ration additive for experimental bull-calves has led to live weight increase in 2 months per 6%, in 4 months per 4.8%, in 8 months per 11.7% and in 12 months per 19% in comparison with the controlled group. Amino-transferases content depending on the nano-metal has increased by the end of the experiment from 2.4% to 8.8% on retention of de Rittis index within the physiological norm. Essential amino acids content in blood has increased per 8%-13%. One can also see mineral substances increase in animals" muscular tissue. Estimation of meat chemical content and some quantitative indexes of meat productivity prove the conclusion about the positive influence of cuprum and cobalt nano-powders fodder additives.

关键词：钴纳米粒子必需氨基酸含量犊牛饲料添加剂肌肉组织生物聚合纳米金属产肉性能

Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase Ⅱ randomised placebo-controlled double-blind multicentre trial

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Stroke & Vascular Neurology 2022年第2期7卷 158-165页

作者： Nawaf Yassi Henry Zhao Leonid churilov Bruce C V Campbell Teddy Wu Henry Ma Andrew Cheung Timothy Kleinig Helen Brown Philip Choi Jiann-Shing Jeng Annemarei Ranta Hao-Kuang Wang Geoffrey C Cloud Rohan Grimley Darshan Shah Neil Spratt Der-Yang Cho Karim Mahawish Lauren Sanders John Worthington Ben Clissold Atte Meretoja Vignan Yogendrakumar Mai Duy Ton Duc Phuc Dang Nguyen Thai My Phuong Huy-Thang Nguyen Chung Y Hsu Gagan Sharma Peter J Mitchell Bernard Yan Mark W Parsons Christopher Levi Geoffrey A Donnan Stephen M Davis Department of Medicine and Neurology Melbourne Brain Centre at The Royal Melbourne HospitalThe University of MelbourneParkvilleVictoriaAustralia Population Health and Immunity Division Walter and Eliza Hall Institute of Medical ResearchParkvilleVictoriaAustralia Ambulance Victoria MelbourneVictoriaAustralia Melbourne Medical School The University of MelbourneMelbourneVictoriaAustralia Stroke Division The Florey Institute of Neuroscience and Mental HealthParkvilleVictoriaAustralia Department of Neurology Christchurch HospitalChristchurchNew Zealand Department of Neurology Monash Medical CentreMonash UniversityClaytonVictoriaAustralia Department of Interventional Neuroradiology Liverpool HospitalLiverpoolNew South WalesAustralia Department of Neurology Royal Adelaide HospitalAdelaideSouth AustraliaAustralia Department of Neurology Princess Alexandra HospitalWoolloongabbaQueenslandAustralia Department of Neurology Box Hill HospitalEastern HealthBox HillVictoriaAustralia Stroke Centre and Department of Neurology National Taiwan University HospitalTaipeiTaiwan Department of Medicine Dunedin School of MedicineUniversity of OtagoWellingtonNew Zealand Department of Neurosurgery E-Da HospitalYanchaoKaohsiungTaiwan Department of Neurology Alfred HospitalMelbourneVictoriaAustralia Department of Clinical Neuroscience Monash University Central Clinical SchoolMelbourneVictoriaAustralia Department of Medicine Sunshine Coast University HospitalNambourQueenslandAustralia Department of Neurology Gold Coast University HospitalSouthportQueenslandAustralia Department of Neurology John Hunter HospitalThe University of NewcastleNewcastleNew South WalesAustralia Department of Neurosurgery China Medical University HospitalTaichungTaiwan Department of Internal Medicine Palmerston North HospitalPalmerston NorthNew Zealand Department of Neurology St Vincent's HospitalFitzroyVictoriaAustralia Department of Neurology Royal Prince Alfred HospitalCamperdownNew South WalesAustra

Rationale Haematoma growth is common early after intracerebral haemorrhage(ICH),and is a key determinant of *** acid,a widely available antifibrinolytic agent with an excellent safety profile,may reduce haematoma *** and design Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units(STOP-MSU)is a phase Ⅱ double-blind,randomised,placebo-controlled,multicentre,international investigator-led clinical trial,conducted within the estimand statistical *** In patients with spontaneous ICH,treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with *** size estimates A sample size of 180 patients(90 in each arm)would be required to detect an absolute difference in the primary outcome of 20%(placebo 39%vs treatment 19%)under a two-tailed significance level of *** adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 *** Participants will receive 1 g intravenous tranexamic acid over 10 min,followed by 1 g intravenous tranexamic acid over 8 hours;or matching *** efficacy measure The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours,defined as either≥33%relative increase or≥6 mL absolute increase in haematoma volume between baseline and follow-up CT *** We describe the rationale and protocol of STOP-MSU,a phase Ⅱ trial of tranexamic acid in patients with ICH within 2 hours from onset,based in participating mobile stroke units and emergency departments.

关键词： placebo centre absolute