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ccdc141 is required for left-right axis development by regulating cilia formation in the Kupffer's vesicle of zebrafish

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Journal of Genetics and Genomics 2024年第9期51卷 934-946页

作者： Pengcheng Wang Wenxiang Shi Sijie Liu Yunjing Shi Xuechao Jiang Fen Li Sun Chen Kun Sun Rang Xu Department of Pediatric Cardiology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Department of Cardiovascular medicine Heart Failure CenterRuijin HospitalRuijin Hospital Lu Wan BranchShanghai Jiao Tong University School of MedicineShanghai 200025China Scientific Research Center Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Department of Pediatric Cardiology Shanghai Children's Medical CenterShanghai Jiao Tong University School of MedicineShanghai 200127China

Laterality is a crucial physiological process intricately linked to the cilium-centrosome complex during embryo *** in the process can result in severe organ ***-coil domain containing 141(CCDC141)has been previously known as a centrosome-related gene,but its role in left-right(LR)asymmetry has not been *** this study,we utilize the zebrafish model and human exome analysis to elucidate the function of ccdc141 in laterality *** knockdown of ccdc141 in zebrafish disrupts early LR signaling pathways,cilia function,and Kupffer's vesicle *** ccdc141-knockdown embryos exhibiting aberrant LR patterns,ccdc141-null mutants show no apparent abnormality,suggesting a genetic compensation response *** parallel,we observe a marked reduction inα-tubulin acetylation levels in the ccdc141 *** treatment with histone deacetylase(HDAC)inhibitors,particularly the HDAC6 inhibitor,rescues the ccdc141 crispant ***,exome analysis of 70 patients with laterality defects reveals an increased burden of CCDC141 mutations,with in-vivo studies verifying the pathogenicity of the patient mutation *** findings highlight the critical role of ccdc141 in ciliogenesis and demonstrate that CCDC141 mutations lead to abnormal LR patterns,identifying it as a candidate gene for laterality defects.

关键词： Left-right axis Cilia WES Laterality defects Zebrafish CCDC141

Multidimensional Analgesia of Acupuncture by Increasing Expression of MD2 in Central Nervous System

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Chinese Journal of Integrative medicine 2024年第11期30卷 1035-1044页

作者： LI Wan-rong REN Lu-lu ZHAO Tian-tian DAI Dan-qing GAO Xiao-fei LIANG Hua-zheng XIONG Li-ze Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation Shanghai Fourth People's Hospital School of Medicine Tongji University Clinical Research Center for Anesthesiology and Perioperative medicine Shanghai Fourth People's Hospital School of Medicine Tongji University Translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People's Hospital School of Medicine Tongji University Department of Anesthesiology and Perioperative medicine Shanghai Fourth People's Hospital School of Medicine Tongji University school of Rehabilitation Southwest Jiaotong University Monash Suzhou Research Institute

Objective:To investigate changes of myeloid differentiation factor 2（MD2） in inflammationinduced pain and acupuncture-mediated ***:Mice were randomly divided into three groups by a random number table method:saline group（n=16）,complete Freund's adjuvant（CFA） group（n=24） and CFA+electroacupuncture（EA） group（n=26）.Inflammation-induced pain was modelled by injecting CFA to the plantar surface of the hind paw of mice and EA was applied to bilateral Zusanli（ST 36） to alleviate *** mice in the CFA+EA group received EA treatment（30 min/d for 2 weeks） 24 h after *** in the saline and CFA groups received sham ***-Frey test and Hargreaves test were used to assess the pain *** and spinal tissues were collected for immunofluorescence staining or Western blotting to quantify changes of MD2 ***:CFA successfully induced plantar pain and EA significantly alleviated pain 3 days after modelling（P0.05）.Fluorescence staining showed significant decrease in the level of MD2 in periagueductal gray（PAG） and locus coeruleus（LC） after CFA injection on day 7（P<0.01 for PAG,P<0.05 for LC） and EA significantly reversed this decrease（P<0.01 for PAG,P<0.05 for LC）.Conclusion:The unique changes of MD2 suggest that EA may exert the analgesic effect through modulating neuronal activities of the superficial laminae of the spinal cord and certai

关键词： dorsal horn electroacupuncture inflammation-induced pain locus coeruleus myeloid differentiation factor 2 periaqueductal gray

Rehmanniae Radix Praeparata aqueous extract improves hepatic ischemia/reperfusion injury by restoring intracellular iron homeostasis

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Chinese Journal of Natural medicines 2024年第9期22卷 769-784页

作者： ZHANG Yinhao JIA Kexin LI Yufei MA Zhi FAN Guifang LUO Ranyi LI Yajing YANG Yang LI Fanghong LIU Runping LIU Jia LI Xiaojiaoyang school of Life Sciences Beijing University of Chinese MedicineBeijing 100029China school of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China Available online 20 Sep.2024

Hepatic ischemia/reperfusion injury(HIRI)is a common pathophysiological condition occurring during or after liver resection and transplantation,leading to hepatic viability impairment and functional ***,ferroptosis,a newly recognized form of programmed cell death,has been implicated in *** Radix Praeparata(RRP),extensively used in Chinese herbal medicine for its hepatoprotective,anti-inflammatory,and antioxidant properties,presents a potential therapeutic ***,the mechanisms by which RRP mitigates HIRI,particularly through the regulation of ferroptosis,remain *** this study,we developed a HIRI mouse model and monocrotaline(MCT)-and erastin-induced in vitro hepatocyte injury *** conducted whole-genome transcriptome analysis to elucidate the protective effects and mechanisms of RRP on *** RRP aqueous extract was characterized by the presence of acteoside,rehmannioside D,and *** results demonstrate that the RRP aqueous extract ameliorated oxidative stress,reduced intracellular iron accumulation,and attenuated HIRI-induced liver ***,RRP significantly inhibited hepatocyte death by restoring intracellular iron homeostasis both in vivo and in ***,the RRP aqueous extract reduced intrahepatocellular iron accumulation by inhibiting ZIP14-mediated iron uptake,promoting hepcidin-and ferroportin-mediated iron efflux,and ameliorating mitochondrial iron aggregation through upregulation of Cisd1 ***,siRNA-mediated inhibition of hamp synergistically enhanced the RRP aqueous extract's inhibitory effect on *** conclusion,our study elucidates the mechanisms by which RRP aqueous extracts alleviate HIRI,highlighting the restoration of iron metabolic *** findings position RRP as a promising candidate for clinical intervention in HIRI treatment.

关键词： Hepatic ischemia/reperfusion injury Rehmanniae Radix Praeparata Ferroptosis Intracellular iron homeostasis

Autophagy in neuroinflammation after traumatic brain injury

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Neural Regeneration Research 2024年第5期19卷 951-952页

作者： Chinmoy Sarkar Marta M.Lipinski Shock Trauma and Anesthesiology Research(STAR)CenterDepartment of AnesthesiologyUniversity of Maryland School of MedicineBaltimoreMDUSA Department of Anatomy and Neurobiology University of Maryland School of MedicineBaltimoreMDUSA

Traumatic brain injury(TBI)is an acquired injury of the brain caused by the impact of external forces on the brain(Maas et al.,2008).It is a major cause of death and disability among people of all ages(Maas et al.,2008).The primary mechanical injury to the brain initiates a cascade of secondary biochemical events that lead to acute and chronic neurodegeneration and activation of inflammatory pathways(Maas et al.,2008).Both brain-resident microglia and blood-derived myeloid cells-macrophages and monocytes that infiltrate the brain due to injury-induced blood-brain barrier damage,contribute to the inflammatory responses after TBI(Morganti et al.,2015).

关键词： damage death after

Interactions Between Extracellular Vesicles and Autophagy in Neuroimmune Disorders

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Neuroscience Bulletin 2024年第7期40卷 992-1006页

作者： Xiwen Ai Haojun Yu Yu Cai Yangtai Guan Department of Neurology Shanghai Jiao Tong University School of Medicine Affiliated Renji HospitalShanghai 200127China Department of Neurology Renaissance School of MedicineStony Brook UniversityStony BrookNY 11794USA

Neuroimmune disorders,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,and Guillain–Barrésyndrome,are characterized by the dysfunction of both the immune system and the nervous *** evidence suggests that extracellular vesicles and autophagy are closely associated with the pathogenesis of these *** this review,we summarize the current understanding of the interactions between extracellular vesicles and autophagy in neuroimmune disorders and discuss their potential diagnostic and therapeutic *** we highlight the need for further research to fully understand the mechanisms underlying these disorders,and to develop new diagnostic and therapeutic strategies.

关键词： Autophagy Extracellular vesicles Neuroimmune disorders Multiple sclerosis Neuromyelitis optica spectrum disorder Myasthenia gravis Guillain-Barrésyndrome

New insights into astrocyte diversity from the lens of transcriptional regulation and their implications for neurodegenerative disease treatments

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Neural Regeneration Research 2024年第11期19卷 2335-2336页

作者： Ibrahim Olabayode Saliu Guoyan Zhao Department of Genetics Washington University School of MedicineSt.LouisMOUSA Department of Neurology Department of Pathology and ImmunologyWashington University School of MedicineSt.LouisMOUSA

Astrocytes are a major glial cell type in the central nervous system,and they provide trophic and metabolic support to *** addition to these roles,they play crucial roles in modulating synaptic functions,development,and pruning(Brandebura et al.,2023).Astrocytes become reactive(activated)by undergoing morphological,molecular,and functional alterations in response to neuropathology such as in injuries and neurodegenerative diseases(NDs)(Escartin et al.,2021).

关键词： degenerative injuries

Simulation-based assessment for the emergency medicine milestones: a national survey of simulation experts and program directors

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World Journal of Emergency medicine 2024年第4期15卷 301-305页

作者： Afrah A Ali Ashley Crimmins Hegang Chen Danya Khoujah Department of Emergency medicine University of Maryland School of MedicineBaltimore 21201USA Department of Epidemiology and Public Health University of Maryland School of MedicineBaltimore 21201USA Department of Emergency medicine AdventHealth TampaTampa 33606USA

The focus of outcome-based education has shifted from the process of training to the end“product”of *** has necessitated a reframing of the teaching,learning,and ***,in 2013,the Accreditation Council for Graduate Medical Education(ACGME)implemented the educational milestones for all accredited residencies and fellowship programs.[1]The milestones have been described as“developmentally based,specialty-specific achievements that residents are expected to demonstrate at established intervals as they progress through training.”[1]Milestones are based on the six core competencies established by the ACGME and American Board of Medical Specialties(ABMS),which consist of medical knowledge(MK),patient care(PC),interpersonal and communication skills(ICS),practice-based learning and improvement(PBLI),professionalism(PROF),and systems-based practice(SBP).[2,3]ACGME,in conjunction with the American Board of Emergency medicine(ABEM),drafted 23 detailed subcompetencies relevant to emergency medicine(EM).[4]

关键词： Miles milestone education

Vascular endothelial growth factor/connective tissue growth factor and proteomic analysis of aqueous humor after intravitreal conbercept for proliferative diabetes retinopathy

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1816-1827页

作者： Hou-Shuo Li Xiao Lyu Ao Rong Yan-Long Bi Wei Xu Hong-Ping Cui Department of Ophthalmology Tongji HospitalSchool of MedicineTongji UniversityShanghai 200065China Department of Ophthalmology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China

AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)following intravitreal injection of ***:This study included 72 PDR patients and 8 cataract patients as *** patients were divided into 3 groups according to the intervals of 3,5,and 7d between intravitreal conbercept(IVC,0.5 mg/0.05 mL)injection and pars plana vitrectomy(PPV)*** humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay(ELISA).The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the data,and the protein interaction network of 23 differential proteins was ***:Post-IVC,VEGF levels decreased and CTGF levels increased significantly in aqueous humor,with the CTGF/VEGF ratio rising significantly at all *** chromatography tandem mass spectrometry(LC-MS/MS)identified differentially expressed proteins between preand post-IVC *** and KEGG analyses revealed involvement in immune response,stress response,complement and coagulation cascades,ferroptosis,and PPAR signaling *** analysis highlighted key proteins like APOA1,C3,and transferrin(TF).ELISA assay confirmed the differential expression of proteins such as HBA1,SERPINA1,COL1A1,and ACTB,with significant changes in the IVC ***:The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels,thereby modifying the CTGF/VEGF ratio,and IVC significantly alters the protein profile in the aqueous humor of patients with *** analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune respons

关键词： proliferative diabetic retinopathy conbercept vascular endothelial growth factor connective tissue growth factor proteomics

Traditional Chinese medicine in the treatment of recurrent respiratory tract infections in children: an overview of systematic reviews and Meta-analyses

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Journal of Traditional Chinese medicine 2024年第5期44卷 871-884页

作者： DENG Yasheng HAN Siyin XI Lanhua HUANG Hui LIANG Tianwei ZHENG Yiqing FAN Yanping LIN Jiang school of Basic Medical Sciences Guangxi University of Chinese Medicine school of Basic Medical Sciences Guangxi University of Chinese MedicineGuangxi Key Laboratory of Marine Drugs Department of Pharmacy Hainan Traditional Chinese Medicine Hospital

OBJECTIVE: To evaluate and summarise the evidence from published Meta-analyses/systematic reviews(MAs/SRs) of Traditional Chinese medicine(TCM) in the treatment of recurrent respiratory tract infections(RRTIs) and to provide a scientific basis for the clinical treatment of RRTIs with TCM. METHODS: Studies were retrieved from Chinese and English databases including the China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database, SinoM ed, PubM ed, Web of Science, the Cochrane Library and EMbase from their establishment date to March 2023. Involved studies were screened, extracted, and evaluated for quality by two researchers independently. The a measurement tool to assess systematic reviews(AMSTAR) 2 scale was used for methodological quality evaluation, as well as the preferred reporting items for systematic reviews and Meta-analyses(PRISMA) 2020 statement for report quality evaluation, the risk of bias in systematic reviews(ROBIS) tool for risk of bias, and the grading of recommendations, assessment, development and evaluation(GRADE) quality assessment tool for evidence quality. RESULTS: Twenty MAs/SRs studies were included, including analyses of 274 original studies involving 38 335 patients with RRTIs. The AMSTAR 2 scale evaluation results showed that 19 studies were of very low quality and one of moderate quality. The ROBIS evaluation results showed that 11 MAs/SRs were at high risk and nine at low risk of bias. The PRISMA 2020 report quality showed the included studies had scores between 23.5 and 35.5, among them one with high quality, 17 with moderate quality and two with low quality. The GRADE system results showed that among 126 outcome indicators, only 17 had moderate quality of evidence, 27 had low quality, 82 had very low quality, and none had high quality. CONCLUSIONS: The MAs/SRs methodological quality of using TCM for treatment RRTIs is generally poor, the quality of reports as well as of evidence is generall

关键词： Meta-analysis child medicine, Chinese traditional randomized controlled trial respiratory tract infections systematic review