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Mutual promotion of mitochondrial fi ssion and oxidative stress contributes to mitochondrial-DNAmediated infl ammation and epithelial-mesenchymal transition in paraquat-induced pulmonary fibrosis

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World Journal of emergency medicine 2023年第3期14卷 209-216页

作者： Jie Zhang Wen-jing Li Shi-qiang Chen Ze Chen Chen Zhang Ran Ying Hong-bing Liu Long-wang Chen Ya-hui Tang Zhong-qiu Lu Guang-ju Zhao Department of emergency medicine the First Affi liated Hospital of Wenzhou Medical UniversityWenzhou 325000China Wenzhou Key laboratory of emergency and Disaster medicine Wenzhou 325000China

BACKGROUND:Pulmonary fibrosis(PF)is one of the main causes of death in patients with paraquat(PQ)poisoning.This study aimed to evaluate the relationship between mitochondrial fi ssion and oxidative stress in PQ-induced epithelial-mesenchymal transition(EMT)and PF.METHODS:C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro.Histological changes in the lungs were examined by hematoxylin and eosin(H&E)staining.Mitochondrial morphology was detected by MitoTracker®Deep Red FM or transmission electron microscopy(TEM).Western blotting and immunofluorescence were used to determine the expression of protein.The migration ability of the cells was detected by the cell scratch test.Mitochondrial DNA(mtDNA)levels were assessed by real-time polymerase chain reaction(PCR).Enzyme-linked immunosorbent assay(ELISA)was applied to detect cytokine levels.Superoxide dismutase(SOD)activity and the levels of glutathione(GSH)and malondialdehyde(MDA)were detected by chemichromatometry.RESULTS:PQ exposure caused EMT and PF in vivo and in vitro.PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1(Drp1),which were accompanied by oxidative stress.Inhibiting mitochondrial fission using mitochondrial division inhibitor-1(Mdivi-1),a selective inhibitor of Drp1,attenuated PQ-induced EMT and oxidative damage.Treatment with N-acetyl-L-cysteine(NAC),an antioxidant,reduced Drp1 expression,attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF.Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release,the expression of Toll-like receptor 9(TLR9)and phosphorylation(P)-NF-κB p65 as well as cytokines(interleukin 6[IL-6],interleukin-1β[IL-1β],and tumor necrosis factor-α[TNF-α])production.CONCLUSION:Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF,which is associated with the mtDNA/TLR9/NF-κB pathway.

关键词： Paraquat Mitochondrial fi ssion Oxidative stress Epithelial-mesenchymal transition Mitochondrial DNA

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The combination of creatine kinase-myocardial band isoenzyme and point-of-care cardiac troponin/contemporary cardiac troponin for the early diagnosis of acute myocardial infarction

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World Journal of emergency medicine 2022年第3期13卷 163-168页

作者： Guang-mei Wang Yong Li Shuo Wu Wen Zheng Jing-jing Ma Feng Xu Jia-qi Zheng He Zhang Jia-li Wang Yu-guo Chen Department of emergency medicine Qilu Hospital of Shandong UniversityJinan 250012China Shandong Provincial Clinical Research Center for emergency and Critical Care medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityChest Pain CenterQilu Hospital of Shandong UniversityJinan 250012China Key laboratory of emergency and Critical Care medicine ofShandong Province Key Laboratory of Cardiopulmonary-cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinan 250012China Key laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry ofEducationChinese Ministry of Health and Chinese Academy of Medical SciencesThe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineQilu Hospital of Shandong UniversityJinan 250012China

BACKGROUND:The early diagnosis of acute myocardial infarction(AMI)remains challenging,especially for institutions without the high-sensitive cardiac troponin(hs-c Tn)assay.Herein,we aim to assess the value of creatine kinase-myocardial band isoenzyme(CK-MB)combined with different cardiac troponin(c Tn)assays in AMI diagnosis.METHODS:This multicenter,observational study included 3,706 patients with acute chest pain from September 1,2015,to September 30,2017.We classified the participants into three groups according to the c Tn assays:the point-of-care c Tn(POC-c Tn)group,the contemporary c Tn(c-c Tn)group,and hs-c Tn group.The diagnostic value was quantified using sensitivity and the area under the curve(AUC).RESULTS:Compared to the single POC-c Tn/c-c Tn assays,combining CK-MB and POC-c Tn/c-c Tn increased the diagnostic sensitivity of AMI(56.1%vs.63.9%,P0.999).In the subgroup analysis,the sensitivity of combining CKMB and c-c Tn increased with time from symptom onset6 h(97.5%vs.98.3%,P=0.317).The AUC of the combination of CK-MB and POC-c Tn significantly increased compared to the single POC-c Tn assay(0.776 vs.0.750,P=0.002).The AUC of the combined CKMB and c-c Tn/hs-c Tn assays did not significantly decrease compared with that of the single c-c Tn/hs-c Tn assays within 6 h.CONCLUSIONS:The combination of CK-MB and POC-c Tn or c-c Tn may be valuable for the early diagnosis of AMI,especially when hs-c Tn is not available.

关键词： Creatine kinase-myocardial band isoenzyme Cardiac troponin Acute myocardial infarction emergency department

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Nutritional status and prognostic factors for mortality in patients admitted to emergency department observation units:a national multi-center study in China

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世界急诊医学杂志(英文) 2023年第1期14卷 17-24页

作者： Hai-jiang Zhou Dong-jing Zuo Da Zhang Xin-hua He Shu-bin Guo Nutrition School of Education College of Chinese emergency medicine Beijing Key Laboratory of Cardio-pulmonary Cerebral ResuscitationEmergency Medicine Clinical Research CenterBeijing Chao-yang HospitalCapital Medical UniversityBeijing 100020China

BACKGROUND:Nutritional risk is common among patients admitted to the emergency department and is associated with adverse clinical outcomes.Despite its large population,few comprehensive studies have been conducted in China concerning the nutritional status of patients admitted to emergency department observation units(EDOUs).METHODS:Patients admitted to EDOUs of 90 tertiary hospitals in China between June 2020 and December 2020 were enrolled.Demographic information,laboratory parameters,nutritional support therapies,and 28-day mortality were recorded.Risk factors for mortality were examined using multi-variateadjusted logistic regression analysis.Receiver operating characteristic(ROC)curves for each predictor of mortality were plotted,and the area under the ROC(AUROC)curves was compared.RESULTS:A total of 2,005 eligible patients were finally enrolled.At the 28-day follow-up,1,911 patients survived,and 94 died.The group with a Nutritional Risk Screening 2002(NRS 2002)score of 3-4 points was the largest(52.01%).The number of patients receiving oral nutritional supplements,enteral nutrition(EN),parenteral nutrition(PN),and the combination of EN and PN was 425,314,853,and 413,respectively.Among the total,77.55%of patients had nutritional risk(NRS 2002≥3).The proportion of patients with high nutritional risk(NRS2002≥5)in the age group>80 years was significantly higher than that in the age group 66-80 years(29.00%vs.23.93%,P=0.032),but not significantly higher than that in the age group 18-65 years(29.00%vs.26.54%,P=0.449).Logistic regression analysis revealed that heart failure(odds ratio[OR]1.856,95%confidence interval[CI]1.087-3.167,P=0.023),consciousness(OR 2.967,95%CI 1.894-4.648,P<0.001),Acute Physiology and Chronic Health Evaluation II(APACHE II)score(OR 1.037,95%CI 1.017-1.058,P<0.001),NRS 2002 score(OR 1.286,95%CI 1.115-1.483,P=0.001),and Mini Nutritional Assessment-Short Form score(OR 0.946,95%CI 0.898-0.997,P=0.039)were all independent risk factors for 28-day mortality.APACHE II and NRS 2002 scores were supe

关键词： Nutritional risk Malnutrition Nutritional Risk Screening 2002 Mini Nutritional Assessment-Short Form

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Trends in point-of-care ultrasound protocols in the emergency department and intensive care unit:a review

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emergency and Critical Care medicine 2023年第2期3卷 64-69页

作者： Xinhui Fan Yuan Bian Guoying Wang Weikang Liu Luyao Gao Yuhui Pan Shengchuan Cao Qiuhuan Yuan Shujian Wei Feng Xu Yuguo Chen Department of emergency and Chest Pain Center Shandong Provincial Clinical Research Center for Emergency and Critical Care MedicineInstitute of Emergency and Critical Care Medicine of Shandong UniversityKey Laboratory of Emergency and Critical Care Medicine of Shandong ProvinceKey Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceQilu Hospital of Shandong UniversityJinanChina.

Together with the development of the focused assessment with sonography for trauma protocol for ultrasound in trauma patients,point-of-care ultrasound is widely used in the field of emergency and critical care medicine.Researchers have established several classic operating protocols for different diseases,such as acute respiratory failure,shock,and cardiac arrest,in the emergency department and intensive care unit.With further development in the portability and popularity of ultrasonic equipment,it is expected to be used as a new type of technology for physical examination,including inspection,palpation,percussion,auscultation,and insonation,which will improve the clinical medicine practice in the future.

关键词： Auscultation and insonation Inspection Palpation Percussion Point-of-care ultrasound Protocol Seven-point and nineplane protocol

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Effects of high-dose glucose-insulin-potassium on acute coronary syndrome patients receiving reperfusion therapy:a meta-analysis

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World Journal of emergency medicine 2024年第3期15卷 181-189页

作者： Zeyu Yang Huiruo Liu Dazhou Lu Shengchuan Cao Feng Xu Chuanbao Li Department of emergency medicine Qilu Hospital of Shandong UniversityJinan 250012China Shandong Provincial Clinical Research Center for emergency and Critical Care medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityChest Pain CenterQilu Hospital of Shandong UniversityJinan 250012China Key laboratory of emergency and Critical Care medicine of Shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinan 250012China Shandong Key laboratory:Magnetic Field-free medicine&Functional Imaging(MF) Qilu Hospital of Shandong UniversityJinan 250012China National Medical Products Administration(NMPA)Key laboratory for Clinical Research and Evaluation of Innovative Drug Qilu Hospital of Shandong UniversityJinan 250012China

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

关键词： Acute coronary syndrome High-dose Glucose-insulin-potassium treatment Reperfusion therapy Meta-analysis

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Overexpression of vascular endothelial growth factor enhances the neuroprotective effects of bone marrow mesenchymal stem cell transplantation in ischemic stroke

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Neural Regeneration Research 2023年第6期18卷 1286-1292页

作者： Cui Liu Zhi-Xiang Yang Si-Qi Zhou Ding Ding Yu-Ting Hu Hong-Ning Yang Dong Han Shu-Qun Hu Xue-Mei Zong Institute of emergency Rescue medicine Emergency Centerthe Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina emergency Department of Affiliated Lianyungang Hospital of Xuzhou Medical University/The First People’s Hospital of Lianyungang LianyungangLianyungangJiangsu ProvinceChina Laboratory of Emergency Medicine Second Clinical Medical College of Xuzhou Medical UniversityXuzhou Medical UniversityXuzhouJiangsu ProvinceChina Key laboratory of Brain Diseases Bioinformation Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina

Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.

关键词： bone marrow mesenchymal stem cell brain-derived neurotrophic factor CD31 microtubule associated protein 2 middle cerebral artery occlusion stroke transplantation vascular endothelial growth factor

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Development and evaluation of a predictive nomogram for survival in heat stroke patients: a retrospective cohort study

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World Journal of emergency medicine 2022年第5期13卷 355-360页

作者： Fei Shao Xian Shi Shu-hua Huo Qing-yu Liu Ji-xue Shi Jian Kang Ping Gong Sheng-tao Yan Guo-xing Wang Li-jie Qin Fei Wang Ke Feng Feng-ying Chen Yong-jie Yin Tao Ma Yan Li Yang Wu Hao Cui Chang-xiao Yu Song Yang Wei Gan Sai Wang Liu-ye-zi Du Ming-chen Zhao Zi-ren Tang Shen Zhao Department of emergency medicine Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China Department of emergency medicine Hebei Yanda HospitalLangfang 065201China Department of emergency medicine Beijing Huairou HospitalBeijing 101400China Department of emergency medicine the Second Hospital of Hebei Medical UniversityShijiazhuang 050000China Department of emergency medicine the Second Affi liated Hospital of Shandong First Medical UniversityTai’an 271000China Department of emergency medicine the First Affi liated Hospital of Dalian Medical UniversityDalian 116011China Department of emergency medicine China-Japan Friendship HospitalBeijing 100029China Department of emergency medicine Beijing Friendship HospitalBeijing 100050China Department of emergency medicine Henan Provincial People’s HospitalZhengzhou 450003China Department of emergency medicine Beijing Tsinghua Changung HospitalBeijing 102218China Department of emergency medicine General Hospital of Ningxia Medical UniversityYinchuan 750004China Department of emergency medicine the Affi liated Hospital of Inner Mongolia Medical UniversityHohhot 010050China Department of emergency medicine the Second Hospital of Jilin UniversityChangchun 130021China Department of emergency medicine the First Hospital of China Medical UniversityShenyang 110001China Department of emergency medicine the Second Hospital of Shanxi Medical UniversityTaiyuan 030001China Department of Big Data Research Goodwill Hessian Health Technology Co.Ltd.Beijing 100085China School of Public Health Peking UniversityBeijing 100083China Beijing Key laboratory of Cardiopulmonary Cerebral Resuscitation Beijing 100020China Department of Critical Care medicine Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China

BACKGROUND:This study aimed to establish an eff ective nomogram to predict the survival of heat stroke(HS)based on risk factors.METHODS:This was a retrospective,observational multicenter cohort study.We analyzed patients diagnosed with HS,who were treated between May 1 and September 30,2018 at 15 tertiary hospitals from 11 cities in Northern China.RESULTS:Among the 175 patients,32 patients(18.29%)died before hospital discharge.After the univariate analysis,mechanical ventilation,initial mean arterial pressure<70 mmHg,maximum heart rate,lab results on day 1(white blood cell count,alanine aminotransferase,creatinine),and Glasgow admission prediction score were included in multivariate analysis.Multivariate Cox regression showed that invasive ventilation,initial mean arterial pressure<70 mmHg(1 mmHg=0.133 kPa),and Glasgow admission prediction score were independent risk factors for HS.The nomogram was established for predicting 7-d and 14-d survival in the training cohort.The nomogram exhibited a concordance index(C-index)of 0.880(95%confidence interval[95%CI]0.831-0.930)by bootstrapping validation(B=1,000).Furthermore,the nomogram performed better when predicting 14-d survival,compared to 7-d survival.The prognostic index cut-off value was set at 2.085,according to the operating characteristic curve for overall survival prediction.The model showed good calibration ability in the internal and external validation datasets.CONCLUSION:A novel nomogram,integrated with prognostic factors,was proposed;it was highly predictive of the survival in HS patients.

关键词： Heat stroke Nomogram Survival Prognosis

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Trends and challenges of emergency and acute care in Chinese mainland:2005–2017

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World Journal of emergency medicine 2021年第1期12卷 5-11页

作者： Chang Pan Jiao-jiao Pang Kai Cheng Feng Xu Yu-guo Chen Department of emergency medicine Qilu Hospital of Shandong UniversityJinan 250012China Shandong Provincial Clinical Research Center for emergency and Critical Care medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityChest Pain CenterQilu Hospital of Shandong UniversityJinan 250012China Key laboratory of emergency and Critical Care medicine of Shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinan 250012China The Key laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of EducationChinese Ministry of Health and Chinese Academy of Medical Sciencesthe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineQilu Hospital of Shandong UniversityJinan 250012China

BACKGROUND:emergency medical service system(EMSS)is essential in providing acute care services for health conditions.However,trends of emergency and acute care in China haven’t been studied systematically.METHODS:Relevant literature was carefully reviewed,including original and review articles,letters,government reports,yearbooks,both in Chinese and in English.Data on the number of emergency visits,physicians and beds in emergency departments(EDs),and the workforce of prehospital emergency care were summarized and analyzed from China Health and Family Planning Statistical Yearbooks(2006–2018).RESULTS:Over the past decade,the number of ED visits tripled from 51.9 million to 166.5 million;and utilization of pre-hospital emergency care increased from 3.2 million to 6.8 million.In response to rapid increases in demand,the number of licensed emergency physicians raised from 20,058 to 59,409;the beds’number increased from 10,783 to 42,367.For pre-hospital emergency care,the volume of health workforce increased from 3,687 to 8,671,with a 109%increase in the number of physicians from 1,774 to 3,712.However,overcrowding,the long length of stay in EDs,poor work environment,and work exhaustion were still the critical challenges faced by China’s EMSS.CONCLUSIONS:The number of emergency visits has grown with continual capability enhancement during the past decade.However,overcrowding,the long length of stay in EDs,poor work environment,and work exhaustion still need to be solved by China’s EMSS.These fi ndings and comparison with the USA could offer experiences and lessons to EMSS development worldwide,especially for developing countries.

关键词： emergency medical service system emergency visits Capabilities Challenges

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The optimal anticoagulation strategy for COVID-19,prophylactic or therapeutic?:a meta-analysis,trial sequential analysis,and meta-regression of more than 27,000 participants

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emergency and Critical Care medicine 2022年第3期2卷 148-166页

作者： Mingyue Guo Qi Han Jiaxuan Xing Feng Xu Jiali Wang Chuanbao Li Zechen Shan Yuan Bian Hao Wang Li Xue Qiuhuan Yuan Chang Pan Yanshan De Xingfang Wang Panpan Hao Shengchuan Cao Jiaojiao Pang Yuguo Chen Department of emergency medicine Qilu Hospital of Shandong UniversityJinanShandongChina Shandong Provincial Clinical Research Center for emergency and Critical Care medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityChest Pain CenterQilu Hospital of Shandong UniversityJinanShandongChina Key laboratory of emergency and Critical Care medicine of Shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinanShandongChina The Key laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of EducationChinese Ministry of Health and Chinese Academy of Medical SciencesThe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineQilu Hospital of Shandong UniversityJinanShandongChina.

Background:Anticoagulants are promising regimens for treating coronavirus disease 2019(COVID-19).However,whether prophylactic or intermediate-to-therapeutic dosage is optimal remains under active discussion.Methods:We comprehensively searched PubMed,Embase,Scopus,Web of Science,Cochrane Library,ClinicalTrials,and MedRxiv databases on April 26,2022.Two independent researchers conducted literature selection and data extraction separately according to predetermined criteria.Notably,this is the first meta-analysis on COVID-19,taking serious consideration regarding the dosage overlap between the 2 comparison groups of prophylactic anticoagulation(PA)and intermediate-to-therapeutic anticoagulation(I-TA).Results:We included 11 randomized controlled trials(RCTs)and 36 cohort studies with 27,051 COVID-19 patients.By analyzing all the RCTs,there was no significant difference in mortality between the PA and I-TA groups,which was further confirmed by trial sequential analysis(TSA)(odds ratio[OR]:0.93;95%confidence interval[CI]:0.71–1.22;P=0.61;TSA adjusted CI:0.71–1.26).The rate of major bleeding was remarkably higher in the I-TA group than in the PA group,despite adjusting for TSA(OR:1.73;95%CI:1.15–2.60;P=0.009;TSA adjusted CI:1.09–2.58).RCTs have supported the beneficial effect of I-TA in reducing thrombotic events.After including all studies,mortality in the I-TA group was significantly higher than in the PA group(OR:1.38;95%CI:1.15–1.66;P=0.0005).The rate of major bleeding was similar to the analysis from RCTs(OR:2.24;95%CI:1.86–2.69;P<0.00001).There was no distinct difference in the rate of thrombotic events between the 2 regimen groups.In addition,in both critical and noncritical subgroups,I-TA failed to reduce mortality but increased major bleeding rate compared with PA,as shown in meta-analysis of all studies,as well as RCTs only.Meta-regression of all studies suggested that there was no relationship between the treatment effect and the overall risk of mortality or major bleeding(P=0.14,P=0.09,respectively).Conclusi

关键词： Anticoagulation COVID-19 Major bleeding Mortality Prophylactic Therapeutic

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Vaspin alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence

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emergency and Critical Care medicine 2024年第1期4卷 4-15页

作者： Haiying Rui Huaxiang Yu Dan Zou Kai Chi Ping Xu Xiaoshuai Song Lulu Liu Xuting Wu Jinxin Wang Li Xue Department of emergency medicine and Chest Pain Center Qilu Hospital of Shandong UniversityJinanShandongChina Shandong Provincial Clinical Research Center for emergency and Critical Care medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityQilu Hospital of Shandong UniversityJinanShandongChina Key laboratory of emergency and Critical Care medicine of Shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinanShandongChina The Key laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of EducationChinese Ministry of Health and Chinese Academy of Medical SciencesThe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineQilu Hospital of Shandong UniversityJinanShandongChina.

Background:Visceral adipose tissue-derived serine protease inhibitor(vaspin),a secretory adipokine,protects against insulin resistance.Recent studies have demonstrated that serum vaspin levels are decreased in patients with coronary artery disease and that vaspin protects against myocardial ischemia-reperfusion injury and atherosclerosis.However,it remains unclear whether vaspin exerts specific effects on pathological cardiac hypertrophy.Methods:An in vivo study was conducted using a cardiac hypertrophy model established by subcutaneous injection of isoproterenol(ISO)in C57BL/6 and vaspin-ko mice.Rapamycin was administered intraperitoneally to mice,for further study.H9c2 cells and neonatal rat ventricular myocytes(NRVMs)were treated with ISO to induce hypertrophy.Human vaspin fusion protein,the proteasome inhibitor MG132,and chloroquine diphosphate were used for further mechanistic studies.Results:Here,we provide the first evidence that vaspin knockdown results in markedly exaggerated cardiac hypertrophy,fibrosis,and cardiomyocyte senescence in mice treated with ISO.Conversely,the administration of exogenous recombinant human vaspin protected NRVMs in vitro against ISO-induced hypertrophy and senescence.Furthermore,vaspin significantly potentiated the ISO-induced decrease in autophagy.Both rapamycin and chloroquine diphosphate regulated autophagy in vivo and in vitro,respectively,and participated in vaspin-mediated cardioprotection.Moreover,the PI3K-AKT-mTOR pathway plays a critical role in vaspin-mediated autophagy in cardiac tissues and NRVMs.Our data showed that vaspin downregulated the p85 and p110 subunits of PI3K by linking p85 and p110 to NEDD4L-mediated ubiquitination degradation.Conclusion:Our results show,for the first time,that vaspin functions as a critical regulator that alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence,providing potential preventive and therapeutic targets for pathological cardiac hypertrophy.

关键词： Autophagic flux Myocardial senescence Pathological cardiac hypertrophy Ubiquitination Vaspin

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