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Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice

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Neuroscience Bulletin 2024年第1期40卷 35-49页

作者： Shuhui Dai Yuan Feng Chuanhao Lu Hongchen Zhang Wenke Ma Wenyu Xie Xiuquan Wu Peng Luo Lei Zhang Fei Fei Zhou Fei Xia Li department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi'an 710000China National Translational Science Center for Molecular medicine and department of Cell Biology Fourth Military Medical UniversityXi'an 710000China department of Neurosurgery The Central Hospital of BaojiBaoji 721000China department of Ophthalmology Xijing HospitalFourth Military Medical UniversityXi'an 710000China

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude *** plays a critical role in ischemic brain injury,but its role in hypo-baric hypoxia(HH)remains *** we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain,and is partially responsible for HH-induced oxidative stress,neuronal loss,and brain *** autophagic agonist rapamycin only promotes the initiation of *** proteome analysis,a screen showed that protein dynamin2(DNM2)potentially regulates autophagic *** of DNM2 significantly increased the formation of autolysosomes,thus maintaining autophagic flux in combination with ***,the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH *** results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

关键词： Autophagy-Proteomics Oxidative stress Hypobaric hypoxia-Brain injury

SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-Yan Shi Yarong Wang Ying Shi Ruofei Tian Xiaohong Chen Hai Zhang Ke Wang Zhinan Chen Ruo Chen National Translational Science Center for Molecular medicine & department of Cell Biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor ***147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism ***,the relationship between the PTMs of CD147 and apoptosis has not been *** our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent ***1 was identified as the methyltransferase catalyzing CD147 to generate ***-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)***,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell *** vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell *** together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

Optimal timing of invasive intervention for high-risk non-ST-segment-elevation myocardial infarction patients

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Journal of Geriatric Cardiology 2024年第8期21卷 807-815页

作者： Juan-Juan ZHENG Yue-Qiao SI Tian-Yang XIA Bing-Jun LU Chun-Yu ZENG Wei-Eric WANG department of Geriatrics Southwest HospitalThird Military Medical UniversityChongqingChina department of Cardiology Daping HospitalThird Military Medical UniversityChongqingChina

OBJECTIVE To compare the immediate,early,and delayed percutaneous coronary intervention(PCI)strategies in non-ST-segment-elevation myocardial infarction(NSTEMI)patients with *** Medical records of patients treated at the Daping Hospital,Third military Medical University,Chongqing,China between 2011 and 2021 were retrospectively *** patients with complete available information were *** patients assigned into three groups based on the timing of PCI including immediate(<2 h),early(2–24 h)and delayed(≥24 h)*** Cox hazards regression and simpler nonlinear models were *** A total of 657 patients were included in the *** median follow-up length was 3.29(interquartile range:1.45–4.85)*** PCI strategy improved the major adverse cardiac event(MACE)outcome compared to the immediate or delayed PCI *** PCI,diabetes mellitus,and left main or/and left anterior descending or/and left circumflex stenosis or/and right coronary artery≥99%were predictors for MACE *** optimal timing range for PCI to reduce MACE risk is 3–14 h *** high-risk NSTEMI patients,early PCI reduced primary clinical outcomes compared to immediate or delayed PCI,and the optimal timing range was 3–14 h *** PCI was superior for NSTEMI with chronic kidney *** Delayed invasive strategy was helpful to reduce the incidence of MACE for high-risk NSTEMI with chronic kidney *** immediate PCI strategy might increase the rate of MACE.

关键词： patients infarction Chongqing

Association between the cumulative triglyceride-glucose index and the recurrence of atrial fibrillation after radiofrequency catheter ablation

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Journal of Geriatric Cardiology 2024年第2期21卷 200-210页

作者： Qing YAN Jia-Qi LIANG Yi-De YUAN Yuan LI Jia-Li FAN Wen-Huan WU Pan XU Jia-Hong XUE department of Cardiovascular medicine the Second Affiliated Hospital of Xi’an Jiaotong UniversityShaanxiChina department of Cardiovascular medicine Zichang People’s HospitalShaanxiChina department of Ultrasound Xijing HospitalAir Force Military Medical UniversityShaanxiChina

BACKGROUND Triglyceride-glucose(TyG)index values are a new surrogate marker for insulin *** study aimed to explore the relationship between cumulative TyG index values and atrial fibrillation(AF)recurrence after radiofrequency catheter ablation(RFCA).METHODS A total of 576 patients with AF who underwent RFCA at the Second Affiliated Hospital of Xi'an Jiaotong University were included in this *** participants were grouped based on cumulative TyG index values tertiles within 3 months after *** regression and restricted cubic spline analyses were used to determine the relationship between cumulative TyG index values and AF *** predictive value of all risk factors was assessed by receiver operating curve *** There were 375 patients completed the study(age:63.23±10.73 years,64.27%male).The risk of AF recurrence increased with increasing cumulative TyG index values *** adjusting for potential confounders,patients in the medium cumulative TyG index group[hazard ratio(HR)=4.949,95%CI:1.778–13.778,P=0.002]and the high cumulative TyG index group(HR=8.716,95%CI:3.371–22.536,P<0.001)had a higher risk of AF recurrence than those in the low cumulative TyG index *** restricted cubic spline regression model also showed an increased risk of AF recurrence with increasing cumulative TyG index *** considering cumulative TyG index values,left atrial diameter,and lactate dehydrogenase levels as a comprehensive factor,the model could effectively predict AF recurrence after RFCA[area under the curve(AUC)=0.847,95%CI:0.797–0.897,P<0.001].CONCLUSIONS Cumulative TyG index values were a risk factor for AF recurrence after *** longitudinal TyG index values may assist with optimized for risk stratification and outcome prediction for AF recurrence.

关键词： atrial fibrillation index

Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 25-34页

作者： Hai-Li Bao Chuan-Zhi Chen Chang-Zhen Ren Ke-Yan Sun Hao Liu Shao-Hua Song Zhi-Ren Fu department of Organ Transplantation Shanghai Changzheng HospitalNavy Military Medical UniversityShanghai 200003China department of Surgical Oncology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Cardiology Shanghai Changzheng HospitalNaval Military Medical UniversityShanghai 200003China department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various ***,little is known about its effect on hepatic ischemia-reperfusion(I/R)*** study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying ***:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R *** alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver *** severity related to the inflammatory response and reactive oxygen species(ROS)production was also ***,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in ***:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and *** oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin *** addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in *** blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling ***:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.

关键词： Hepatic ischemia-reperfusion injury Polydatin Macrophage Polarization Inflammation

Nanoparticle targeting cGAS-STING signaling in disease therapy

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Nano Research 2024年第8期17卷 7315-7336页

作者： Lan Zhou Yu Huang Yuzhang Wu Shupei Tang Frontier Medical Training Brigade Third Military Medical UniversityHutubi 831200China department of Gastroenterology Xinqiao HospitalThird Military Medical UniversityChongqing 400037China Institute of Immunology Third Military Medical UniversityChongqing 400038China Shigatse Branch Xinqiao HospitalThird Military Medical UniversityShigatse 857000China

The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon(IFN)genes(cGAS-STING)signaling pathway is crucial for sensing abnormal DNA accumulation in the *** binds to abnormal DNA,cGAS catalyzes the production of second messenger cyclic dinucleotides,followed by the activation of downstream *** activation induces the expression of type I interferon and other inflammatory cytokines,ultimately initiating an immune *** to the involvement of the cGAS-STING pathway in various diseases,including infection,tumor,autoimmune disease and kidney disease,ongoing research is focused on developing drugs and treatment methods to target and regulate this *** the development of nanotechnology,nanomedicines targeting cGAS-STING signaling are of great significance in clinical applications due to their targeted delivery,controlled drug release,improved solubility,multifunctionality,and enhanced *** comprehensive review focuses on the most recent progress of nanoplatforms targeting cGAS-STING in disease therapy,aiming to provide references and guidelines for further design and optimization of nanomedicines.

关键词： nanomedicine cGAS-STING pathway and related disease anti-tumor nanotherapy anti-viral nanotherapy

Depletion of anti-CD47mAb in plasma by genetically modified cells for pre-transfusion testing

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Genes & Diseases 2024年第5期11卷 102-104页

作者： Fei Wang Wenting Wang Xiaoshuang Wu Zhixin Liu Yafen Wang Rong Zhang Shunli Gu Qunxing An Yaozhen Chen Xingbin Hu department of Transfusion medicine Xijing HospitalFourth Military Medical UniversityXi’anShaanxi 710032China Xi’an Medical University Xi’anShaanxi 710021China

Allogeneic red blood cell(RBC)transfusion is commonly performed in medical practice because of its efficacy and low-risk ***,pre-transfusion tests are susceptible to monoclonal antibody(mAb)interference.1 Currently,mAb therapies are being developed to treat many diseases,such as ***,certain mAbs,such as anti-CD38mAb and anti-CD47mAb,can bind to RBC membranes;this binding interferes with pre-transfusion tests.2 CD47 has gained considerable attention in recent years because of its potential as a therapeutic target for hematologic malignancies and solid tumors.3 The binding of anti-CD47mAb to RBCs may lead to false-positive results in pan-agglutination tests and cause delays and risks in establishing compatible RBCs for transfusion.

关键词： CD47 transfusion diseases

ADAR1 Inhibits Macrophage Apoptosis and Alleviates Sepsis-induced Liver Injury Through miR-122/BCL2A1 Signaling

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Journal of Clinical and Translational Hepatology 2024年第2期12卷 134-150页

作者： Shanshou Liu Jiangang Xie Chujun Duan Xiaojun Zhao Zhusheng Feng Zheng Dai Xu Luo Yu Li Minghe Yang Ran Zhuang Junjie Li Wen Yin Emergency department Xijing HospitalFourth Military Medical UniversityXi’anShaanxiChina Emergency department Tangdu HospitalFourth Military Medical UniversityXi’anShaanxiChina Third Student Brigade School of Basic Medical ScienceFourth Military Medical UniversityXi’anShaanxiChina department of Immunology Fourth Military Medical UniversityXi’anShaanxiChina

apoptosis plays regulatory roles in the pathogenesis of immunosuppression and organ *** previously reported that adenosine deaminases acting on RNA-1(ADAR1)reduced intestinal and splenic inflammatory damage during ***,the roles and mechanism of ADAR1 in sepsis-induced liver injury remain ***:We performed transcriptome and single-cell RNA sequencing of peripheral blood mononuclear cells(PBMCs)from patients with sepsis to investigate the effects of ADAR1 on immune cell *** also employed a cecal ligation and puncture(CLP)sepsis mouse model to evaluate the roles of ADAR1 in sepsisinduced liver ***,we treated murine RAW 264.7 macrophages with lipopolysaccharide to explore the underlying ADAR1-mediated mechanisms in ***:PBMCs from patients with sepsis had obvious apoptotic morphological ***-cell RNA sequencing indicated that apoptosis-related pathways were enriched in monocytes,with significantly elevated ADAR1 and BCL2A1 expression in severe ***-induced septic mice had aggravated liver injury and Kupffer cell apoptosis that were largely alleviated by ADAR1 ***1 directly bound to premiR-122 to modulate miR-122 ***-122 was an upstream regulator of ***,ADAR1 also reduced macrophage apoptosis in mice with CLP-induced sepsis through the miR-122/BCL2A1 signaling pathway and protected against sepsis-induced liver ***:The findings show that ADAR1 alleviates macrophage apoptosis and sepsis-induced liver damage through the miR-122/BCL2A1 signaling *** study provides novel insights into the development of therapeutic interventions in sepsis.

关键词： Sepsis Macrophage ADAR1 microRNA122 BCL2A1 Apoptosis

Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

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Neural Regeneration Research 2024年第7期19卷 1608-1617页

作者： Yanan Dou Xiaowei Fei Xin He Yu Huan Jialiang Wei Xiuquan Wu Weihao Lyu Zhou Fei Xia Li Fei Fei department of Neurosurgery Xijing HospitalAir Force Military Medical UniversityXi’anShaanxi ProvinceChina department of Ophthalmology Xijing HospitalAir Force Military Medical UniversityXi’anShaanxi ProvinceChina

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual *** is repo rted to play a protective role in neuroinflammation in the ***,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain *** our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion *** in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller *** found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion ***,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte *** opposite results we re observed with Homerla ove ***,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion *** together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

关键词： caspase-8 Homer1a interleukin-18 interleukin-1β intraocular pressure ischemia/reperfusion injury JSH-23 Müller cells NLRP3 nuclear factor-kB p65 retina