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CAF-derived exosome-miR-3124-5p promotes malignant biological processes in NSCLC via the TOLLIP/TLR4-MyD88-NF-κB pathway

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Oncology Research 2025年第1期33卷 133-148页

作者： TAO SUN QINGHUA SONG HUA LIU Department of Respiratory and Critical Care medicine Affiliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong226001China Department of emergency The People’s Hospital of RugaoNantong226500China Department of Haematology The People’s Hospital of RugaoNantong226500China

Background:Lung cancer is a life-threatening disease that occurs worldwide,but is especially common in *** crucial role of the tumour microenvironment(TME)in non-small cell lung cancer(NSCLC)has attracted recent ***-associated fibroblasts(CAFs)are the main factors that contribute to the TME function,and CAF exosomes are closely linked to ***:The expression levels of miR-3124-5p and Toll-interacting protein(TOLLIP)were analysed by bioinformatics prediction combined with RT-qPCR/Western Blot *** were isolated and identified from clinical NSCLC *** electron microscopy and Western Blot were used to identify exosomes from these *** in proliferation(CCK-8 and clone formation),migration(wound healing),and invasion(transwell)of NSCLC cells were *** Luciferase reporter test was applied to clarify the binding of miR-3124-5p to *** TOLLIP/TLR4/MyD88/NF-κB pathway proteins were determined using Western blot ***:MiR-3124-5p is overexpressed in clinical tissues and cells of ***-3124-5p was dramatically enriched in CAF-derived *** experiments revealed that CAFs delivered miR-3124-5p into NSCLC cells via exosomes,stimulating cancer cell ***-3124-5p acted as a sponge to negatively regulate TOLLIP expression,which activated the TLR4/MyD88/NF-κB axis to promote the occurrence and development of *** salvage tests were performed to determine whether CAF-exosome-derived miR-3124-5p plays a pro-cancer role in NSCLC by affecting the TOLLIP signalling ***:These results provide an interesting direction for the diagnosis and therapy of NSCLC.

关键词： Non-small cell lung cancer(NSCLC) Cancer-associated fibroblasts(CAFs) Exosomes miR-3124-5p Toll-interacting protein(TOLLIP)

Advances and challenges in peroral endoscopic myotomy:Safety,precision,and post-procedure management

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World Journal of Gastroenterology 2025年第5期31卷 1-6页

作者： Grigorios Christodoulidis Kyriaki Tsagkidou Konstantinos Eleftherios Koumarelas Marina Nektaria Kouliou Department of General Surgery University Hospital of LarissaLarissa 41110Greece Department of Gastroenterology General Hospital of LarissaLarisa 41221ThessalíaGreece Department of emergency medicine General Hospital of LarissaLarissa 41221Greece

Peroral endoscopic myotomy(POEM)has revolutionized the treatment of upper gastrointestinal tract motility disorders,particularly *** editorial explores the efficacy,safety,and challenges of POEM,emphasizing its role as a primary treatment with excellent long-term outcomes and minimal adverse *** evolution of POEM underscores the need for precision in myotomy techniques and the importance of interdisciplinary collaboration,especially regar-ding anesthetic *** significant advances,challenges remain in standardizing safety protocols and managing *** POEM appli-cations expand,precision endoscopy continues to enhance therapeutic outcomes,promising a transformative impact on gastrointestinal motility disorder manage-ment.

关键词： Peroral endoscopic myotomy Complications after peroral endoscopic myoto-my Procedural safety Interdisciplinary collaboration Adverse events Therapeutic out-comes

Anticipation for hepatic arterial infusion chemotherapy in the treatment of hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 304-310页

作者： Grigorios Christodoulidis Dimitra Bartzi Konstantinos E Koumarelas Department of General Surgery University Hospital of LarissaLarissa 41335Greece Department of Oncology The 251 Airforce General HospitalAthens 11525Greece Department of emergency medicine General Hospital of LarissaLarissa 41221Greece

Hepatic arterial infusion chemotherapy (HAIC) is an advanced targeted therapeuticapproach for hepatocellular carcinoma (HCC), the most common type ofprimary liver cancer. HAIC has demonstrated significant potential in managingadvanced HCC, particularly in regions with high prevalence rates. Despite itspromise, several challenges and areas for future research remain. Clinical studieshave substantiated the efficacy of HAIC in enhancing survival outcomes forpatients with advanced hepatic carcinoma. Notably, combination therapiesinvolving immune checkpoint inhibitors, such as lenvatinib and programmeddeath-1 inhibitors, have shown substantial improvements in median overallsurvival and progression-free survival compared to systemic *** combination therapies have also exhibited superior response rates anddisease control, with manageable and often less severe adverse events relative tosystemic treatments. This article is based on the review by Zhou et al and aims todiscuss the current status and future directions in the treatment of HCC, emphasizingthe role of HAIC and its integration with novel therapeutic agents.

关键词： Hepatocellular carcinoma Hepatic arterial infusion chemotherapy Targeted therapy Challenges Safety Advantages

Prehospital critical care drug-therapy and 30-day mortality in patients with acute respiratory disease

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World Journal of emergency medicine 2025年第1期16卷 43-50页

作者： Jesús Jurado-Palomo JoséLuis Martín-Conty Begoña Polonio-López Cristina Rivera Picón Raúl López-Izquierdo Carlos del Pozo Vegas Pedro Ángel de Santos Castro Ancor Sanz-García Francisco Martín-Rodríguez Technological Innovation Applied to Health Research Group(ITAS) Faculty of Health SciencesCastilla-La Mancha UniversityTalavera de la Reina 45600Spain Nuestra Señora del Prado General Hospital Talavera de la Reina 45600Spain emergency Department Rio Hortega University HospitalValladolid 47012Spain CIBER of Respiratory Diseases(CIBERES) Institute of Health Carlos ⅢMadrid 28029Spain Faculty of medicine University of ValladolidValladolid 470003Spain emergency Department University Clinical HospitalValladolid 47003Spain Prehospital emergency Medical Services(SACYL) Valladolid 47007Spain

BACKGROUND: Prehospital medication is a reality, and the role of these therapies must be explored to assess their validity, especially for acute respiratory diseases, which are usually associated with increased morbidity. The aim of this study was to examine the association of prehospital medication use with mortality in patients with acute respiratory ***: A prospective, multicenter, emergency medical service(EMS) delivery cohort study was carried out in adults with unselected respiratory diseases managed by EMS who were transferred to the emergency department. From January 1, 2019, to October 31, 2023, six advanced life support units, thirty-eight basic life support units, and four hospitals in Spain participated in the study. Demographic data, vital signs, use of mechanical ventilation, prehospital respiratory diagnosis, and prehospital medication were collected. The primary outcome was 30-day in-hospital ***: A total of 961 patients were included, with a mortality rate of 17.5%(168 patients). Age, an increasing number of comorbidities, the use of invasive mechanical ventilation(IMV), the use of major analgesics, hypnotics, and bicarbonate were risk factors. In contrast, elevated systolic blood pressure and Glasgow Coma Scale scores were found to be protective factors against mortality. The predictive capacity of the model reached an area under the curve(AUC) of 0.857(95% confidence interval [95% CI] 0.827–0.888).CONCLUSION: Our data revealed that IMV, major analgesics, hypnotics and bicarbonate administration were associated with elevated mortality. Adding prehospital drug therapy information to demographic variables and vital signs could improve EMS decision-making, allowing a better characterization of patients at risk of clinical worsening.

关键词： Drug-therapy Medication Prehospital Mortality emergency medical services

Evaluation of influence of detrending CSES satellite data on lithospheric magnetic field modeling

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Earth and Planetary Physics 2025年第02期 346-356页

作者： Jie Wang YanYan Yang ZhiMa Zeren JianPing Huang HengXin Lu National Institute of Natural Hazards Ministry of Emergency Management of China

The China Seismo-Electromagnetic Satellite(CSES) was successfully launched in February 2018. The high precision magnetometer(HPM) on board the CSES has captured high-quality magnetic data that have been used to derive a global lithospheric magnetic field model. While preparing the datasets for this lithospheric magnetic field model, researchers found that they still contained prominent residual trends within the magnetic anomaly even once signals from other sources had been eliminated. However, no processing was undertaken to deal with the residual trends during modeling to avoid subjective processing and represent the realistic nature of the data. In this work, we analyze the influence of these residual trends on the lithospheric magnetic field *** of orders 0–3 were used to fit the trend of each track and remove it for detrending. We then derived four models through detrending-based processing, and compared their power spectra and grid maps with those of the CSES original model and CHAOS-7model. The misfit between the model and the dataset decreased after detrending the data, and the convergence of the inverted spherical harmonic coefficients improved. However, detrending reduced the signal strength and the power spectrum, while detrending based on high-order polynomials introduced prominent distortions in details of the magnetic anomaly. Based on this analysis, we recommend along-track detrending by using a zero-order polynomial(removing a constant value) on the CSES magnetic anomaly data to drag its mean value to zero. This would lead to only a slight reduction in the signal strength while significantly improving the stability of the inverted coefficients and details of the anomaly.

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Incorporating red blanket protocol within code crimson:Streamlining definitive trauma care amid the chaos

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World Journal of Critical Care medicine 2025年第1期14卷 14-19页

作者： Sohil Pothiawala Savitha Bhagvan Andrew MacCormick emergency medicine Woodlands HealthSingapore 737628Singapore Trauma and emergency Services Auckland City HospitalAuckland 1023New Zealand Department of General Surgery Middlemore HospitalAuckland 2025New Zealand

The care of a patient involved in major trauma with exsanguinating haemorrhage is time-critical to achieve definitive haemorrhage control,and it requires coordinated multidisciplinary *** initial resuscitation of a patient in the emergency department(ED),Code Crimson activation facilitates rapid decisionmaking by multi-disciplinary specialists for definitive haemorrhage control in operating theatre(OT)and/or interventional radiology(IR)*** this decision has been made,there may still be various factors that lead to delay in transporting the patient from ED to OT/*** Blanket protocol identifies and addresses these factors and processes which cause delay,and aims to facilitate rapid and safe transport of the haemodynamically unstable patient from ED to OT,while minimizing delay in resuscitation during the *** two processes,Code Crimson and Red Blanket,complement each *** would be ideal to merge the two processes into a single protocol rather than having two separate *** these quality improvement strategies and coor-dinated processes within the trauma framework of the hospitals/healthcare systems will help in further improving the multi-disciplinary care for the complex trauma patients requiring rapid and definitive haemorrhage control.

关键词： Red blanket protocol Code crimson Haemorrhage Trauma

T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

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Neural Regeneration Research 2025年第5期20卷 1277-1292页

作者： Yuxiao Zheng Zilin Ren Ying Liu Juntang Yan Congai Chen Yanhui He Yuyu Shi Fafeng Cheng Qingguo Wang Changxiang Li Xueqian Wang School of Traditional Chinese medicine Beijing University of Chinese MedicineBeijingChina Library Beijing University of Chinese MedicineBeijingChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue *** the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the *** an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune *** review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic *** found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic ***1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain ***2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain *** interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke *** trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic ***,such studies have been relatively infrequent,and clinical experience is still *** summary,in ischemic stroke,T cell subsets and activated micro

关键词： brain immune inflammation interaction ischemic stroke mechanism microglia neuron secondary injury T cells

Mechanism of AsperosaponinⅥRelated to EGFR/MMP9/AKT/PI3K Pathway in Treatment of Rheumtoid Arthritis

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Chinese Journal of Integrative medicine 2025年第2期31卷 131-141页

作者： LUO Jin-fang YU Yang LIU Jian-xin School of Basic medicine Guizhou University of Traditional Chinese MedicineGuiyang(550025)China Sino-Pakistan Center on Traditional Chinese medicine China-Pakistan International Science and Technology Innovation Cooperation Base for Ethnic Medicine Development in Hunan ProvinceSchool of Pharmaceutical SciencesHunan University of MedicineHuaihua CityHunan Province(418000)China

Objective:To explore the mechanism of action of asperosaponinⅥ(AⅥ)in the treatment of rheumatoid arthritis(RA)and validate it in ex vivo experiments using network pharmacology and molecular docking ***:The predicted targets of AⅥwere obtained from PharmMaper,UniProt and Swiss Target Prediction platforms,the disease targets were collected from Online Mendelian Inheritance in Man,Therapeutic Target Database and Gene Cards databases,the intersection targets of AⅥand RA were obtained from Venny 2.1.0,and the protein-protein interaction(PPI)network was obtained from STRING database,which was analyzed by Cytoscape software and screened to obtain the core *** software was used to analyze PPI network and screen the core *** on the Database for Annotation,Visualization and Integrated Discovery database,Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed,and Cytoscape software was used to construct the"DiseasePathway-Target-Drug"network,which was finally verified by molecular docking and animal ***:Network pharmacological studies showed that AⅥwas able to modulate 289 targets,with 102 targets for the potential treatment of RA,with the core pathway being the AKT/PI3K signaling pathway,and the core targets being the epidermal growth factor receptor(EGFR)and matrix metalloproteinase 9(MMP9).Molecular docking results showed that AⅥcould produce strong binding with both of the 2 core *** vitro cellular experiments showed that AⅥreduced nitric oxide,prostaglandin E_2,tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and IL-1βlevels(P<0.05)and inhibited cyclooxygenase-2,nitric oxide synthase,EGFR,MMP9,phosphorylated phosphoinositide 3-kinase(p-PI3K),and phosphorylated serine-threonine kinase(p-AKT)proteins(P<0.05).The results of in vivo studies showed that AⅥimproved RA score and foot swelling thickness and decreased TNF-α,IL-6,p-PI3K and p-AKT levels in RA rat

关键词： inflammation rheumatoid arthritis network pharmacology asperosaponinⅥ EGFR/MMP9/AKT/PI3K pathway

Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

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Neural Regeneration Research 2025年第8期20卷 2153-2168页

作者： Xinyu You Lin Niu Jiafeng Fu Shining Ge Jiangwei Shi Yanjun Zhang Pengwei Zhuang National Key Laboratory of Chinese medicine Modernization Tianjin University of Traditional Chinese MedicineTianjinChina Haihe Laboratory of Modern Chinese medicine Tianjin University of Traditional Chinese MedicineTianjinChina First Teaching Hospital of Tianjin University of Traditional Chinese medicine TianjinChina National Clinical Research Center for Chinese medicine Acupuncture and Moxibustion TianjinChina

Traumatic brain injury is a prevalent disorder of the central nervous *** addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are *** dysfunction is a significant consequence of traumatic brain *** the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous *** gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated *** comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut ***,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain *** review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effec

关键词： traumatic brain injury brain-gut-microbiome axis gut microbiota neuroimmune immunosuppression host defense vagal afferents bacterial infection dorsal root ganglia nociception neural circuitry