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Advantages of nanocarriers for basic research in the field of traumatic brain injury

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Neural Regeneration Research 2024年第2期19卷 237-245页

作者： Xingshuang Song Yizhi Zhang Ziyan Tang Lina Du School of Pharmaceutical Sciences Shandong University of Traditional Chinese MedicineJinanShandong ProvinceChina Department of Pharmaceutics Beijing Institute of Radiation MedicineBeijingChina

A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.

关键词： blood-brain barriers brain targeting central nervous system extracellular vesicles inflammatory factor microglial cell nanocarriers nanoparticles neural restoration traumatic brain injury

SARS-CoV-2 and innate immunity:the good,the bad,and the"goldilocks"

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Cellular & Molecular Immunology 2024年第2期21卷 171-183页

作者： Benjamin L.Sievers Mark T.K.Cheng Kata Csiba Bo Meng Ravindra K.Gupta Department of medicine University of CambridgeCambridgeUK Cambridge institute of Therapeutic Immunology&Infectious Disease(CITID) Department of MedicineUniversity of CambridgeCambridgeUk

An ancient conflict between hosts and pathogens has driven the innate and adaptive arms of immunity.Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that can be leveraged therapeutically.The humoral response to SARS-CoV-2 infection has been the focus of intense research,and the role of the innate immune system has received significantly less attention.Here,we review current knowledge of the innate immune response to SARS-CoV-2 infection and the various means SARS-CoV-2 employs to evade innate defense systems.We also consider the role of innate immunity in SARS-CoV-2 vaccines and in the phenomenon of long COVID.

关键词： SARS-CoV-2 Innate immune response Interferon Cytokines Inflammation Antiviral targets

More common RNAemia in the early stage of severe SARS-CoV-2 BF.7.14 infections in pediatric patients

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Biosafety and Health 2024年第1期6卷 5-11页

作者： Yu Sun Runan Zhu Yang Pan Ri De Shuang Liu Liping Jia Bing Lv Xiaoyun Li Dongmei Chen Yao Yao Dong Qu Daitao Zhang Linqing Zhao Laboratory of Virology Bejing Key Laboratory of Etiology of Viral Diseases in ChildrenCapital Institute of PediatricsBejing 100020China institute for Infectious Disease and Endemic Disease Control Bejing Center for Disease Control and Prevention Beijing 100013China Department of Intensive Care Unit Affiliated Children's Hospital of Capital Institute of PediatricsBeijing 100020China

The risk factors of severe infections in children during the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)outbreak in Beijing remain elusive.SARS‐CoV‐2‐positive children admitted to the intensive care unit(ICU)with collected plasma specimens were enrolled and screened for common pathogens using capillary electrophoresis‐based multiplex PCR from December 12,2022,to January 24,2023.The SARS‐CoV‐2 subvariants were identified using next‐generation sequencing.Plasma was positive for two(positive;P),one(suspicious;S),or no(negative;N)SARS‐CoV‐2 genes were classified as plasmatic RNA‐positive(RNAemia;P+S)or without RNAemia(N).Clinical and laboratory data of the enrolled cases were then collected and analyzed.The 34 enrolled children included 26 males and 24 younger than three years.All were negative for other respiratory pathogens.BF.7.14(18/29)was the predominant subvariant.Viral loads in respiratory specimens,hours from symptom onset to the first respiratory specimen collection(time‐variable),with comorbidities and BF.7.14 and BA.5.2 distributions were significantly different in P vs.N and RNAemia vs.without RNAemia group.Among most cases,the T lymphocyte ratios decreased,while the cytokine level and the B lymphocyte ratio increased.The time variables were 2.22±2.05 and 4.00±2.49 days in BF.7.14 and BA.5.2 infections,respectively.In conclusion,SARS‐CoV‐2 was more likely to cause severe infections among males aged≤3 years old with comorbidities during the SARS‐CoV‐2 outbreak in Beijing,while RNAemia is more common in children at the early stage of severe BF.7.14 infections,and most had high cytokine levels and B‐cell activation.

关键词： Severe SARS‐CoV‐2 infection Pediatric patients Risk factor RNAemia BF.7.14

Impact of exercise on markers of B cell-related immunity:A systematic review

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Journal of Sport and Health Science 2024年第3期13卷 339-352,I0002页

作者： David Walzik Sergen Belen Karen Wilisch Marie Kupjetz Silvana Kirschke Tobias Esser Niklas Joisten Alexander Schenk Sebastian Proschinger Philipp Zimmer Division of Performance and Health(Sports medicine) Institute for Sport and Sport ScienceTU Dortmund UniversityDortmund 44227Germany

Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are lacking.This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human biofluids.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,MEDLINE,Web of Science,and Embase were searched on March 8,2023.Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were included.Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise.Study characteristics,outcome measures,and statistically significant changes were summarized tabularly.Results:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise training.All included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control conditions.Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.Conclusion:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities.Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.

关键词： Antibody B-lymphocyte Exercise Humoral immunity Immune system

Trends in Respiratory Infectious Pathogens in Children Under the Age of 14—Xiamen City,Fujian Province,China,2017-2023

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China CDC weekly 2024年第8期6卷 143-147页

作者： Jiali Cao Jie Pan Xiaoqing Yang Jumei Liu Min Zhu Zeyu Zhao Ling Chen Tianmu Chen Huiming Ye Department of Laboratory medicine Fujian Key Clinical Specialty of Laboratory MedicineWomen and Children’s HospitalSchool of MedicineXiamen UniversityXiamen CityFujian ProvinceChina State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen CityFujian ProvinceChina Department of pediatrics Women and Children's HospitalSchool of MedicineXiamen UniversityXiamen CityFujian ProvinceChina

Summary What is already known about this topic?Respiratory infections pose a significant burden on public health.Despite recent outbreaks occurring in various locations,there is limited information available on the pr... 详细信息

关键词： Xiamen spite Fujian

Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

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Neural Regeneration Research 2024年第8期19卷 1686-1695页

作者： Avery L.Miller Nathan K.Evanson J.Michael Taylor University of Cincinnati College of medicine CincinnatiOHUSA Department of pediatrics University of CincinnatiCincinnatiOHUSA Department of Neurology and Rehabilitation medicine University of CincinnatiCincinnatiOHUSA Division of Pediatric Rehabilitation medicine Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA Division of Neurology Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

关键词： acetylcholinesterase inhibitor adult cognition donepezil pediatrics traumatic brain injury

Efficacy and safety of Huzhang Granule,a compound Chinese herbal medicine,for acute gouty arthritis:A double-blind,randomized controlled trial

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Journal of Integrative medicine 2024年第3期22卷 270-278页

作者： Hao Wang Si-ting Chen Xiao-jie Ding Le Kuai Liang Hua Xin Li Yi-fei Wang Ming Zhang Bin Li Rui-ping Wang Mi Zhou Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China institute of Dermatology Shanghai Academy of Traditional Chinese MedicineShanghai 201203China Department of Dermatology the Affiliated Hospital of Jiangxi University of Chinese MedicineNanchang 330000Jiangxi ProvinceChina Shanghai Skin Disease Hospital School of MedicineTongji UniversityShanghai 200443China institute of Dermatology School of MedicineTongji UniversityShanghai 200443China

Background:Acute gouty arthritis(AGA)is an inflammatory joint disease with a high prevalence.Typical medical interventions,including nonsteroidal anti-inflammatory drugs,colchicine and glucocorticoids,can have serious adverse reactions.Huzhang Granule(HZG),a compound Chinese herbal medicine,has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions.However,the efficacy and safety of HZG in AGA patients remains unknown.Objective:The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients.Design,setting,participants and interventions:The current study was conducted as a noninferiority,randomized controlled clinical trial on 180 eligible enrolled participants.Participants were randomly assigned into the HZG and etoricoxib groups.Treatments were administered for 5 d,during which the HZG group received HZG and placebo etoricoxib,while the etoricoxib group received etoricoxib and placebo HZG in the same ratio(1:1).Main outcome measures:The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window.The pain level was measured via a visual analogue scale,ranging from 0 mm to 100 mm.The secondary outcomes comprised joint tenderness and swelling,reduction of inflammatory biomarkers,and the patient’s and investigator’s global evaluations of therapeutic response.Results:The mean reduction in pain was-51.22 mm(95%confidence interval[CI],[-53.42,-49.03]mm)for the HZG and-52.00 mm(95%CI,[-54.06,-49.94]mm)for the etoricoxib groups.The mean difference between the two groups was 0.78 mm(95%CI,[-2.25,3.81]mm).All additional efficacy endpoints,covering decreased inflammation and pain relief,yielded compelling proof of noninferiority.Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group(4.44%vs 13.33%;P≤0.05).Conclusion:HZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness

关键词： Acute gouty arthritis Huzhang Granule Randomized controlled trial Blind

Exposure to ephedrine attenuates Th1/Th2 imbalance underlying OVA-induced asthma through airway epithelial cell-derived exo-somal lnc-TRPM2-AS

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Chinese Journal of Natural medicines 2024年第6期22卷 530-540页

作者： HU Yan WANG Mengqing XIE Jing JIAO Luojia DING Yi LUO Yinhe Department of pediatrics The First Hospital of Hunan University of Chinese MedicineChangsha 410007China Hunan University of Chinese medicine Changsha 410208China Department of Rehabilitation Medical CollegeChangsha Civil Affairs Vocational and Technical CollegeChangsha 410004Hunan ProvinceChina Teaching and Research Office of Chinese and Western Combination Hunan University of Chinese MedicineChangsha 410208China

Although various anti-inflammatory medications,such as ephedrine,are employed to manage cough-variant asthma,their underlying mechanisms are yet to be fully understood.Recent studies suggest that exosomes derived from airway epithelial cells(AECs)contain components like messenger RNAs(mRNAs),micro-RNAs(miRNAs),and long noncoding RNA(lncRNA),which play roles in the occurrence and progression of airway inflammation.This study investigates the influence of AEC-derived exosomes on the efficacy of ephedrine in treating cough-variant asthma.We established a mouse model of asthma and measured airway resist-ance and serum inflammatory cell levels.Real-time polymerase chain reaction(RT-qPCR),Western blotting,and enzyme-linked im-munosorbent assay(ELISA)analyses were used to assess gene and protein expression levels.Exosomes were isolated and character-ized.RNA immunoprecipitation(RIP)and RNA pull-down assays were conducted to examine the interaction between hnRNPA2B1 and lnc-TRPM2-AS1.In the ovalbumin(OVA)-challenged mouse model,ephedrine treatment reduced inflammatory responses,air-way resistance,and Th1/Th2 cell imbalance.Exosomes from OVA-treated AECs showed elevated levels of lnc-TRPM2-AS1,which were diminished following ephedrine treatment.The exosomal lnc-TRPM2-AS1 mediated the Th1/Th2 imbalance in CD4^(+)T cells,with its packaging into exosomes being facilitated by hnRNPA2B1.This study unveils a novel mechanism by which ephedrine ameli-orates OVA-induced CD4^(+)T cell imbalance by suppressing AEC-derived exosomal lnc-TRPM2-AS1.These findings could provide a theoretical framework for using ephedrine in asthma treatment.

关键词： Asthma Ephedrine Exosomal lnc-TRPM2-AS1 Th1/Th2 imbalance HnRNPA2B1 Airway epithelial cells

(+)/(-)-Gerbeloid A,a pair of unprecedented coumarin-based polycyclic meroterpenoid enantiomers from Gerbera piloselloides:Structural elucidation,semi-synthesis,and lipid-lowering activity

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2657-2668页

作者： Chenxu Zhao Jingrong Li Yue Hu Lingyu Li Meng Yu Yunfeng Huang Tao Zhang Hai Shang Zhongmei Zou State Key Laboratory of Bioactive Substance and Function of Natural medicines Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China institute of Chinese medicine Resources Guangxi Institute of Chinese Medicine&Pharmaceutical ScienceNanning 530000China

A pair of coumarin-based polycyclic meroterpenoid enantiomers(+)/(-)-gerbeloid A[(+)-1a and(-)-1b]were isolated from the medicinal plant Gerbera piloselloides,which have a unique caged oxatricyclo[4.***.2.0^(3,8)]decene scaffold.Their planar and three-dimensional structures were exhaustively characterized by comprehensive spectroscopic data and X-ray diffraction analysis.Guided by the hypothetical biosynthetic pathway,the biomimetic synthesis of racemic 1 was achieved using 4-hydroxy-5-methylcoumarin and citral as the starting material via oxa-6πelectrocyclization and intramolecular[2+2]photocycloaddition.Subsequently,the results of the biological activity assay demonstrated that both(+)-1a and(-)-1b exhibited potent lipid-lowering effects in 3T3-L1 adipocytes and the high-fat diet zebrafish model.Notably,the lipid-lowering activity of(+)-1a is better than that of(-)-1b at the same concentration,and molecular mechanism study has shown that(+)-1a and(-)-1b impairs adipocyte differentiation and stimulate lipolysis by regulating C/EBPα/PPARγsignaling and Perilipin signaling in vitro and in vivo.Our findings provide a promising drug model molecule for the treatment of obesity.

关键词： Gerbera piloselloides Natural products Coumarin meroterpenoid Structural elucidation Biomimetic synthesis Lipid-lowering activity 3T3-L1 adipocytes High-fat diet zebrafish model