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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse school of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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A dry-electrode enabled ECG-on-Chip with arrhythmia-aware data transmission

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Science China(Information Sciences) 2025年

作者： Xinzi XU Yanxing SUO Yang ZHAO Peiyi ZHOU Xiao HAN Qiao CAI Min WANG Jiajun YUAN Liebin ZHAO Yongfu LI Guoxing WANG Yong LIAN Department of Micro-Nano Electronics and MoE Key Lab of Artificial Intelligence Shanghai Jiao Tong University Pediatric AI Clinical Application and Research Center Shanghai Engineering Research Center of Intelligence Pediatrics (SERCIP) Child Health Advocacy Institute Shanghai Children's Medical Center School of MedicineShanghai Jiao Tong University Shanghai Engineering Research Center of Intelligence pediatrics (SERCIP) Xin Hua Hospital Affiliate to Shanghai Jiao Tong University School of Medicine

Early detection and treatment of cardiovascular diseases (CVDs) can be significantly enhanced through the use of flexible wearable electrocardiogram (ECG) sensors, potentially reducing CVD-related mortality. This paper introduces an ECG-on-Chip (EoC) solution tailored for flexible ECG sensors, incorporating novel features to address common challenges in wearable ECG technology. The EoC integrates a chopper-stabilized capacitively-coupled instrumentation amplifier (CS-CCIA),ensuring a high common-mode rejection ratio (CMRR) and low noise performance. Performance is further boosted via a positive feedback loop (PFL) and a programmable gain amplifier (PGA) with shared on-chip calibration logic, which enhances input impedance and minimizes gain variability to ensure consistent algorithm performance. Additionally, a secondary chopping technique is employed to further reduce noise, achieving an input-referred noise level of 454 nVrms. The embedded algorithm within the EoC is designed to extract clinically meaningful features, facilitating robust real-time arrhythmia analysis. Fabricated using a 0.18μm CMOS process, the EoC consumes 14.9μW with a supply voltage of 1.2 V. The algorithm’s efficacy has been validated over 0.4 million heartbeats, demonstrating a sensitivity of over 99.7%for R-peak detection and 98.3%for arrhythmia analysis. To demonstrate practical application, the EoC has been integrated with a commercial Bluetooth low energy (BLE)transceiver, forming a wireless arrhythmia monitoring sensor equipped with dry electrodes. This system consumes 292.04μW in arrhythmia-aware transmission mode, supporting 13 days of operation with a 30 mAh thin-film battery.

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Pathways towards Precision Medicine in Cancer Management Using Genomic Information

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Journal of Genetics and Genomics 2015年第10期42卷 515-515,516页

作者： Jingwu Xie Department of pediatrics Wells Center for Pediatrics Research Indiana University School of Medicine

Cancer research over the last few decades indicates that cancer is a genetic disease. In fact, the discovery of the most advanced targeted therapy of cancer comes from cancer ge- netics/genomics studies. This year marks the 20th anniversary for the invention of imatinib mesylate, which targets primarily the BCR-ABL kinase in Philadelphia chromosome-positive chronic myelogenous leukemia （CML）. Philadelphia chro- mosome is the most significant chromosomal aberration in leukemia, and imayinib mesylate is regarded as the first small molecule targeting mutant kinases in cancer. In the last few years, additional therapeutic drugs have been developed to target mutant EGFR and ALK fusion proteins in lung adeno- carcinomas. Thus, understanding the genomic aberrations has huge impacts on clinical management of cancer.

关键词： In gene EGFR XPC lung

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Effects of environmental stressors on stem cells

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World Journal of Stem Cells 2019年第9期11卷 565-577页

作者： Jessica R Worley Graham C Parker Department of pediatrics Wayne State University School of Medicine

Environmental toxicants are ubiquitous,and many are known to cause harmful health ***,much of what we know or think we know concerning the targets and long-term effects of exposure to environmental stressors is sadly *** exposure may have health effects that are currently mischaracterized or at least mechanistically incompletely *** much of the recent excitement about stem cells(SCs)focuses on their potential as therapeutic agents,they also offer a valuable resource to give us insight into the mechanisms and risks of toxicant *** only as a response to the increasing ethical pressure to reduce animal testing,SC studies allow us valuable insight into the true effects of human exposure to environmental stressors under controlled *** present a review of the history of publications on the effects of environmental stressors on SCs,followed by a consolidation of the literature over the past five years on a subset of key environmental stressors of importance to human health and their effects on both embryonic and tissue *** review will make constructive suggestions as to areas of toxicant research where further studies are needed,as well as making indications of the potential utility for advancing knowledge and directing research on environmental toxicology.

关键词： Environmental substances Toxic Stem cells Endocrine disruptors Alcohols Tobacco smoking Metals Heavy Particulate matter Volatile organic compounds Ozone

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A time for cocktails and inclusion

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Neural Regeneration Research 2018年第6期13卷 987-988页

作者： Shenandoah Robinson Frances J.Northington Lauren L.Jantzie Division of Pediatric Neurosurgery Johns Hopkins University School of Medicine Division of Neonatology Department of Pediatrics Johns Hopkins University School of Medicine Departments of pediatrics and Neurosciences University of New Mexico School of Medicine

Perinatal brain injury（PBI）is one of the most important causes of lifelong deficits in cognition,behavior,social interaction and motor skills,as well as *** encompasses,but is not limited to,hypoxic-ischemic encepha... 详细信息

关键词： PBI www HIE EPO A time for cocktails and inclusion

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Saccharomyces boulardii as a single trigger of food protein-induced enterocolitis syndrome: Seven case reports

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World Journal of Clinical Cases 2025年第6期13卷 35-40页

作者： Jin-Bok Hwang Hyo-Jeong Jang Department of pediatrics Keimyung University School of MedicineDongsan Medical CenterDaegu 42601South Korea

BACKGROUND Food protein-induced enterocolitis syndrome(FPIES)is the most serious type of non-immunoglobulin E(IgE)-mediated food allergic reaction manifesting as sepsis-like symptom,which can lead to *** boulardii(***),a probiotic prescribed frequently in clinical settings,has been reported to trigger FPIES in an infant with soy-triggered *** this report,we describe a new clinical FPIES in which *** was the sole triggering factor of acute FPIES adverse reaction in seven healthy *** SUMMARY Seven FPIES cases triggered by only *** were gathered from 2011 to the *** of the patients had previously experienced any allergic reaction to cow’s milk,soy,or complementary *** age of the patients was 4-10-months old,and the symptoms of FPIES developed after ingestion of ***,which is mostly prescribed for the treatment of gastroenteritis or antibiotic-associated *** patients experienced severe repetitive vomiting 1-3 hours after *** *** lethargy,marked pallor,and cyanosis were also *** IgE-mediated hypersensitivity developed in any *** was followed by initial intense vomiting in approximately 5-10 hours after *** ingestion,and only one case showed bloody,purulent,and foul-smelling *** patients stabilized quickly,mostly within 6 *** got all improved within 24 hours after discontinuation of *** *** can be the sole trigger of acute FPIES and be prescribed cautiously even in healthy children without FPIES.

关键词： Food protein-induced enterocolitis syndrome Food hypersensitivity Saccharomyces boulardii Probiotics Child Case report

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Yin-Yang and Zheng:Exported from Chinese Medicine

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Chinese Journal of Integrative Medicine 2014年第4期20卷 250-255页

作者：张红激王展翔 Department of Otolaryngology Indiana University School of Medicine Department of pediatrics Indiana University School of Medicine

Chinese medicine （CM） basic theory differs substantially from modernmedicine in methodology. CM views the healthy human body as an entity in yin-yang equilibrium. CM practitioners typically diagnose patients with ＂Zheng （CMsyndrome）＂-yin-yang status of specific organs, and the ultimate goal of treatment inCM is to restore the yin-yang balance. This concept might seem strange to Westernperceptions; however, CM philosophy and methodology have been graduallyaccepted and used in the West. There is growing evidence from prestigiousworldwide journals like Nature, Science and Cell indicating that CM theory isbecoming an important component in dealing with health issues in the West.

关键词： Chinese medicine Syndrome basic theory yin-yang Zheng West medicine integration

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Suicide attempt using potassium tablets for congenital chloride diarrhea:A case report

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World Journal of Clinical Cases 2020年第8期8卷 1463-1470页

作者： Shigeo Iijima Department of pediatrics Hamamatsu University School of MedicineHamamatsu 4313192Japan

BACKGROUND Congenital chloride diarrhea(CCD)is a rare inherited disorder of intestinal electrolyte transport that results in a large wastage of electrolytes and *** in substitution therapy using sodium chloride(NaCl)and potassium chloride(KCl)have dramatically improved survival for patients with *** KCl is widely prescribed as a potassium supplement;however,it has also occasionally been used in suicide attempts,as potassium poisoning can generate life-threatening *** SUMMARY A 26-year-old female presented to the emergency department(ED)with selfpoisoning,having taken 30 tablets of slow-release KCl(total:240 mmol potassium)following an auditory *** patient had been undergoing substitution therapy with NaCl and KCl for CCD and been followed up in the pediatric *** month prior,she developed insomnia and anxiety and had consulted a *** the ED,although her general condition was good,she appeared *** serum potassium level was 7.0 mmol/L,indicating hyperkalemia,and electrocardiographic changes showed tenting of the *** responded to the administration of calcium gluconate,sodium bicarbonate,and insulin with glucose,and the serum potassium level ***,she was diagnosed with *** In CCD management,physicians should pay careful attention to patients’extraintestinal issues,including psychological disorders that may emerge in adulthood.

关键词： Congenital chloride diarrhea Substitution therapy Suicide Potassium overdose Schizophrenia Case report

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Genetics in medical school curriculum:A look at the University of Rochester school of Medicine and Dentistry

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2008年第1期9卷 10-15页

作者： Deanne M. ROBINSON Chin-To FONG Department of pediatrics University of Rochester School of Medicine and DentistryRochesterNY 14642USA

Genetics is assuming an increasingly important role in medicine. As a result,the teaching of genetics should also be increased proportionally to ensure that future physicians will be able to take advantage of the new genetic technology,and to understand the associated ethical,legal and social issues. At the University of Rochester school of Medicine and Dentistry,we have been able to incorporate genetic education into a four-year medical curriculum in a fully integrated fashion. This model may serve as a template for other medical curriculum still in development.

关键词： Genetics education Medical education Curriculum reform

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Protein-loosing enteropathy associated with rotavirus infection in an infant

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World Journal of Gastroenterology 2008年第10期14卷 1630-1632页

作者： Tadashi Iwasa Nobuyuki Matsubayashi Department of pediatrics Mie University Graduate School of Medicine Tsu Mie Japan Department of pediatrics Shima Prefectural Hospital Shima Mie Japan

Rotavirus is an acute enteric pathogen in infants and children. We reported a rare case of a 6-mo-old infant with protein-loosing enteropathy (PLE) caused by rotavirus gastroenteritis, and evaluated the immunological profile in peripheral blood lymphocytes. Laboratory examinations showed lymphopenia, hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and elevation of alpha-1-antitrypsin (α1-AT) clearance. Lymphocytes subpopulation study revealed the reversal of CD4+/CD8+ ratio with the selective decrease of CD4- positive lymphocytes. Moreover, the excessive increase of T cells producing IFN-gamma (IFN-γ) was found, which plays an important role in the protection against viral infection. The primary or secondary activation of immune system by rotavirus may influence structural integrity and vascular permeability, which may play a triggering role in protein-loosing enteropathy.

关键词： Protein-loosing enteropathy Rotavirus Lymphocytes producing IFN-γ Alpha-1-antitrypsin Reversal of CD4+/CD8+ ratio

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