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Screening optimal target populations with symptomatic bradyarrhythmia for pharmacotherapy:a discriminant analysis pilot study

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Journal of Traditional Chinese Medicine 2025年第1期45卷 160-166页

作者： ZHANG Wantong YI Danhui LU Fang YANG Qiaoning SHI Shuai LI Qiuyan WENG Weiliang WANG Xujie ZHU Baochen Institute of clinical pharmacology Xiyuan HospitalChina Academy of Chinese Medical Sciences NMPA Key Laboratory for clinical research and Evaluation of Traditional Chinese Medicine National clinical research Center for Chinese Medicine Cardiology Xiyuan HospitalChina Academy of Chinese Medical Sciences School of Statistics Renmin University of China Department of General Medicine Guanganmen HospitalChina Academy of Chinese Medical Sciences Department of Pharmacy Dongzhimen HospitalBeijing University of Chinese Medicine

OBJECTIVE: To screen the target population with symptomatic bradyarrhythmia for pharmacotherapy. METHODS: This study use database from clinical trial that use Yuanjiang decoction(元姜方), a traditional Chinese medicinal prescription. Eligible participants were recruited and treated with Yuanjiang decoction(composed of 6 Chinese herbal medicines), 200 m L twice daily. Cross-contingency analysis, logistic regression analysis, interaction analysis, discriminant analysis and 10-fold cross validation methods were used to establish discriminant model. RESULTS: This study concluded that the clinical treatment of bradyarrhythmia has a clear effect. Low minimum heart rate, high maximum heart rate are risk factors that affect the efficacy. Patients with only one comorbid disease did not significantly affect the efficacy, but patient with two or more diseases of coronary heart disease, hypertension, paroxysmal atrial fibrillation, premature ventricular contraction and premature atrial contraction at the same time did not have a good effect. Using the discriminant analysis method to establish a efficacy prediction model, y = 0.07X1 + 0.16X2-0.65X3-1.12X4-0.71X5-0.75X6-0.91X7(X1 = 24 h mean heart rate, X2 = minimum heart rate, X3 = coronary heart disease, X4 = paroxysmal atrial fibrillation, X5 = premature ventricular contraction, X6= sinus block, X7 = atrioventricular block). CONCLUSION: Our model based on the clinical features of patients with bradyarrhythmia. Should be useful aid for predicting pharmacotherapy response and could screen the optimal pharmacotherapy target.

关键词： bradycardia discriminant analysis drug therapy health services needs and demand medicine, Chinese traditional

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Copper homeostasis and neurodegenerative diseases

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Neural Regeneration research 2025年第11期20卷 3124-3143页

作者： Yuanyuan Wang Daidi Li Kaifei Xu Guoqing Wang Feng Zhang International research Laboratory of Ethnomedicine of Ministry of Education Key Laboratory of Basic Pharmacology of Ministry of EducationLaboratory Animal Center and Key Laboratory of Basic Pharmacology of Guizhou ProvinceZunyi Medical UniversityZunyiGuizhou ProvinceChina

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of *** homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and *** in copper homeostasis can lead to either the deficiency or accumulation of copper in brain *** evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative ***,the exact mechanisms underlying these processes are not *** is a potent oxidant that increases reactive oxygen species production and promotes oxidative *** reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial *** oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory ***,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell *** study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease *** synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of heredit

关键词： Alzheimer's disease amyotrophic lateral sclerosis disease copper homeostasis copper toxicity Huntington's disease Menkes'disease multiple sclerosis neurodegenerative disease Parkinson's disease Wilson's disease

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Context-dependent role of sirtuin 2 in inflammation

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Neural Regeneration research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado Elena Puerta Department of Pharmaceutical Sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra Institute for Health research(IdiSNA) PamplonaSpain

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NLRP3 nuclear factorκB sirtuin 2

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Targeting Epac2 and GluA3-containing AMPARs:a novel therapeutic strategy for Alzheimer's disease

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Neural Regeneration research 2025年第11期20卷 3223-3224页

作者： Tong Zhang Martina Schmidt Department of Molecular pharmacology Groningen Research Institute of PharmacyUniversity of GroningenGroningenThe Netherlands School of Pharmacy Tianjin Medical UniversityTianjinChina

Alzheimer's disease(AD)is a neurodegenerative disease that manifests progressive decline in memory and *** the early stage of AD,memory retrieval is impaired preceding memory acquisition and consolidation(Roy et al.,2016).Prior to the onset of symptoms,pathological amyloid-β(Aβ)plagues and tau protein tangles accumulate in extracellular and intracellular spaces,respectively,leading to *** these hallmark pathologies,Aβ is proposed to be the primary etiology by triggering a cascade of pathogenic events,including neuroinflammation,oxidative stress,tau hyperphosphorylation,synaptic/neuronal dysfunction,and neuronal death(Zhang et al.,2023b).

关键词： Alzheimer impaired Aβ

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A Two-Pronged Approach to Security of Discrete-Event Systems

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Journal of Systems Science & Complexity 2025年第01期 178-209页

作者： MATSUI Shoma RUDIE Karen CAI Kai Department of Electrical and Computer Engineering & the Ingenuity Labs research Institute Queen's University Department of core Informatics Osaka Metropolitan University

This paper investigates a security problem of simultaneously addressing two types of attacks: Eavesdropping and infiltration. The authors model the target system as a discrete-event system(DES) with subsets of concealable events and protectable events, in order to make the proposed methodology applicable to various practical systems and employ two existing works of DES security: Degree of opacity and state protection. Specifically, the authors consider that all protectable events are observable, and some observable events are concealable. In addition, protectable events cannot be protected once they are concealed. Given such a constraint, the goal is to figure out which events to conceal and which transitions to protect so that the prescribed requirements of degree of opacity and state protection are satisfied. In this work the authors decide which events to conceal as all transitions of a given event label are concealed or not concealed. The proposed problem formulation also requires a solution to only involve absolutely necessary protectable events in order for the system to avoid superfluous protection costs. The authors first examine a general version of our security problem with an intuitive algorithm to compute acceptable solutions, and then present a special version which results in a reduced computation time compared to the general version.

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Characterization of nonlinear spectral linewidth and light shift in diffuse laser-cooled atoms

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Chinese Physics B 2025年第2期34卷 250-255页

作者： Yiran Yin An-Ning Xu Jin Peng Bei Liu Key Laboratory of Laser and Infrared System Ministry of EducationCenter for Optics Research and Engineering(CORE)Shandong UniversityQingdao 266237China

We demonstrate an integrating sphere to cool~(87)Rb atoms and measure the recoil-induced resonance and electromagnetically induced absorption *** measure the relationship between their linewidth and light shift with variation of the detuning and power of the cooling laser and study the performance of the diffuse laser cooling mechanism by the absorption linewidth radio?ν_E/?ν_R and light shift|?_R-?_E|using nonlinear ***,when?ν_E/?ν_R reaches a value of 1.57,the temperature and number of cold atoms achieve the optimal cooling *** characterization of absorption linewidth and light shift will provide a method to estimate whether diffuse light cooling achieves the best cooling effect,contributing to the future development of isotropic laser cooling for application in quantum sensing.

关键词： nonlinear spectrum diffuse laser cooling temperature measurement

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The loaded matrix:neurotrophin-enriched hydrogels for stem cell brain repair in Parkinson's disease

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Neural Regeneration research 2025年第8期20卷 2315-2316页

作者： Giulia Comini Eilis Dowd pharmacology&Therapeutics University of GalwayGalwayIreland

More than 200 years after Parkinson's disease was first described by the English surgeon whose name would eventually be given to the condition,available treatments remain purely symptomatic,leaving a critical unmet cl... 详细信息

关键词： clinical loaded eventually

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Compartmentalized regulation of organelle integrity in neurodegenerative diseases:lessons from the Drosophila motor neuron

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Neural Regeneration research 2025年第1期20卷 195-196页

作者： Hyun Sung Department of Neurology Johns Hopkins University School of MedicineBaltimoreMDUSA Medical research Institute and Department of PharmacologyPusan National University School of MedicineYangsanRepublic of Korea

Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell *** this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal *** some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal *** example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).

关键词： organelle regulation distribution

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Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

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Neural Regeneration research 2025年第3期20卷 763-778页

作者： Minghuang Gao Xinyue Wang Shijie Su Weicheng Feng Yaona Lai Kongli Huang Dandan Cao Qi Wang Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina Institute of clinical pharmacology Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina The Sixth Affiliated Hospital Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

关键词： central nervous system meningeal lymphatic vessels immunity myeloid cells lymphatic cells neurodegenerative disease

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A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration research 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd pharmacology&Therapeutics and Galway Neuroscience Center University of GalwayGalwayIreland

Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged from<1% to 500% of cells transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

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