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HIF-1αpromotes virus replication and cytokine storm in H1N1 virus-induced severe pneumonia through cellular metabolic reprogramming

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Virologica Sinica 2024年第1期39卷 81-96页

作者： Xiaoxiao Meng Yong Zhu Wenyu Yang Jiaxiang Zhang Wei Jin Rui Tian Zhengfeng Yang Ruilan Wang department of critical care medicine Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China Precision Research Center for Refractory Diseases Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China

The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine ***,the specific mechanisms triggering virus replication and cytokine storm are still not fully ***,we identified hypoxia inducible factor-1α(HIF-1α)as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial ***,HIF-1αprotein expression is upregulated after H1N1 *** of HIF-1αattenuates pulmonary injury,viral replication and cytokine storm in *** addition,viral replication and cytokine storm were inhibited after HIF-1αknockdown in ***,the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis,with rapid production of ATP and *** of glycolysis significantly suppresses viral replication and inflammatory *** analysis revealed that H1N1-induced HIF-1αcan promote the expression of hexokinase 2(HK2),the key enzyme of glycolysis,and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate,which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/β*** conclusion,this study demonstrated that the upregulation of HIF-1αby H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2,providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection.

关键词： H1N1 Severe pneumonia Virus replication Hypoxia inducible factor-1α Glycolysis

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Efficacy and safety of Nafamostat mesylate in patients with endstage renal failure

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World Journal of Clinical Cases 2024年第1期12卷 68-75页

作者： Kun Liu Zhen-Hua Li department of critical care medicine The Third People's Hospital Of Hubei ProvinceWuhan 430030Hubei ProvinceChina department of critical care medicine General Hospital of The Yangtze River ShippingWuhan Brain HospitalWuhan 430015Hubei ProvinceChina

BACKGROUND Recent studies on dialysis anticoagulation therapy in patients with renal failure have shown that Nafamostat mesylate,a broad-spectrum potent serine protease inhibitor,has strong anticoagulation and anti-fiber *** To evaluate the efficacy and safety of Nafamostat mesylate in patients with end-stage renal *** Seventy-five patients with end-stage renal failure who received hemodialysis at our hospital between January 2020 and August 2021 were selected and divided into the observation group(Nafamostat mesylate for injection,n=33)and control group(heparin sodium injection,n=32).general patient data,indicators of clinical efficacy,dialyzer hemocoagulation parameters,coagulation function indices,and hemoglobin concentration and platelet count before and after treatment,and the occurrence of adverse reactions after treatment were compared between the two *** The two groups showed no significant differences in general patient data(P>0.05).The post-treatment effectiveness rate in the control group was lower than that in the observation group(P0.05),while the number of patients in grade 0 was lower in the control group,and the number of patients in grades II and III was higher in the control group(P0.05).The total number of post-treatment adverse reactions in the observation group was lower than that in the control group(P<0.05).CONCLUSION Treatment of patients showing end-stage renal failure with Nafamostat mesylate can s

关键词： End-stage renal failure Nafamostat mesylate Effectiveness Safety study Chronic kidney diseases

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Tissue-resident macrophages exacerbate lung injury after remote sterile damage

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Cellular & Molecular Immunology 2024年第4期21卷 332-348页

作者： Hanhui Zhong Jingjing Ji Jinling Zhuang Ziying Xiong Pengyun Xie Xiaolei Liu Jundi Zheng Wangli Tian Xiaoyang Hong Jing Tang The department of Anesthesiology Affiliated Hospital of Guangdong Medical UniversityZhanjiangGuangdongChina The department of critical care medicine General Hospital of Southern Theater Command of PLAGuangzhouChina The department of Respiratory medicine Guangdong Provincial Hospital of Integrated Chinese and Western MedicineFoshanChina Pediatric Intensive care Unit Senior Department of Pediatricsthe Seventh Medical Center of PLA General HospitalBeijingChina

Remote organ injury,which is a common secondary complication of sterile tissue damage,is a major cause of poor prognosis and is difficult to ***,we report the critical role of tissue-resident macrophages in lung injury after trauma or stroke through the inflammatory *** found that depleting tissue-resident macrophages rather than disrupting the recruitment of monocyte-derived macrophages attenuated lung injury after trauma or *** findings revealed that the release of circulating alarmins from sites of distant sterile tissue damage triggered an inflammatory response in lung-resident macrophages by binding to receptor for advanced glycation end products(RAGE)on the membrane,which activated epidermal growth factor receptor(EGFR).Mechanistically,ligand-activated RAGE triggered EGFR activation through an interaction,leading to Rab5-mediated RAGE internalization and EGFR phosphorylation,which subsequently recruited and activated P38;this,in turn,promoted RAGE translation and trafficking to the plasma membrane to increase the cellular response to RAGE ligands,consequently exacerbating *** study also showed that the loss of RAGE or EGFR expression by adoptive transfer of macrophages,blocking the function of RAGE with a neutralizing antibody,or pharmacological inhibition of EGFR activation in macrophages could protect against trauma-or stroke-induced remote lung ***,our study revealed that targeting the RAGE-EGFR signaling pathway in tissue-resident macrophages is a potential therapeutic approach for treating secondary complications of sterile damage.

关键词： tissue-resident macrophage RAGE remote sterile damage

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Data driven analysis reveals prognostic genes and immunological targets in human sepsis-associated acute kidney injury

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World Journal of Emergency medicine 2024年第2期15卷 91-97页

作者： Qing Zhao Jinfu Ma Jianguo Xiao Zhe Feng Hui Liu department of Diagnosis and Treatment of Cadres the First Medical CenterChinese PLA General HospitalBeijing 100853China Intensive care Unit the 305th Hospital of Chinese PLABeijing 100032China department of critical care medicine the First Medical CenterChinese PLA General HospitalBeijing 100853China Nephrology department the First Medical CenterChinese PLA General HospitalBeijing 100853China

BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is *** analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of ***:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)*** identified the co-DEGs and constructed a gene co-expression network to screen the hub *** analyzed immune correlations and disease correlations and performed functional annotation of the hub *** also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription ***,we conducted a correlation analysis to evaluate the role of the hub ***:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney ***,IL32 was significantly associated with mortality in SA-AKI ***,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI ***32 expression increased significantly in the kidney of septic ***-like receptor 2(TLR2)was significantly and negatively correlated with ***:IL32 is the key gene involved in SA-AKI and is significantly associated with ***2 and relevant immune cells are closely related to key genes.

关键词： Sepsis Acute kidney injury Interleukin 32 Toll-like receptor 2 Bioinformatics analysis

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Bronchobiliary fistula in a patient with liver cancer

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 523-525页

作者： Yao-Xin Chen Zhi-Hua Deng Hao Zhao Bi-Ying Zhou Jing-Jing Guo Gang Zeng Jin-Xian Qian department of Respiratory and critical care medicine Suzhou Municipal Hospital Affiliated to Nanjing Medical UniversitySuzhou 215000China

Bronchobiliary fistula(BBF) is a pathologic channel between the biliary tract and bronchial tree. In general, congenital BBF is relatively rare in adult patients. There are a few case reports suggesting that BBF is mainly secondary to hepatobiliary diseases, such as biliary obstruction, tumor, surgery, or liver abscess, and liver tumor is the predominant causative factor [1]. In addition, with the increasing number of liver and biliary surgeries and interventional therapies in recent years, more cases of BBF were reported as a postoperative complication [ 2, 3 ]. In this case, we presented a patient who underwent interventional treatment for liver tumor and was treated for his respiratory symptoms but diagnosed with BBF finally. Here, we summarized the clinical features and main diagnostic procedures of the case, aiming to provide evidence for early identification and diagnosis of BBF.

关键词： biliary fistula diagnosis

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Unresectable hepatocellular carcinoma:Transarterial chemoembolization combined with lenvatinib in combination with programmed death-1 inhibition is a possible approach

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World Journal of Gastrointestinal Oncology 2024年第10期16卷 4042-4044页

作者： Fei-Yu Zhao Dong-Yu Wang Nian-Song Qian department of Thoracic Oncology Respiratory and Critical Care MedicineThe Eighth Medical Center of People’s Liberation Army General HospitalBeijing 100853China department of Nephrology General Hospital of the People’s Liberation ArmyBeijing 100853China Senior department of Thoracic Oncology Respiratory and Critical Care MedicineThe Eighth Medical Center of People’s Liberation Army General HospitalBeijing 100091China

In this editorial,we review the article“Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma”.We specifically focused on whether transarterial chemoembolization combined with lenvatinib in combination with a programmed death 1 inhibitor could be used in patients with unresectable hepatocellular *** both transarterial chemoembolization as well as lenvatinib in combination with programmed death 1 inhibitors play an important role in the treatment of advanced liver cancer,but the combination of all three therapeutic approaches needs more research.

关键词： Transarterial chemoembolization Programmed death 1 Lenvatinib Hepatocellular carcinoma

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Machine learning and bioinformatics to identify biomarkers in response to Burkholderia pseudomallei infection in mice

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BIOCELL 2024年第4期48卷 613-621页

作者： YAO FANG FEI XIA FEIFEI TIAN L EI QU FANG YANG JUAN FANG ZHENHONG HU HAICHAO LIU department of Respiratory and critical care medicine General Hospital of Center Theater of PLAWuhan430070China School of medicine Wuhan University of Science and TechnologyWuhan430065China School of Life Science and Engineering Southwest Jiaotong UniversityChengdu611756China

Objective:In the realm of Class I pathogens,Burkholderia pseudomallei(BP)stands out for its propensity to induce severe *** the intricate interactions between BP and host cells is imperative for comprehending the dynamics of BP infection and discerning biomarkers indicative of the host cell response ***:mRNA extraction from BP-infected mouse macrophages constituted the initial step of our *** gene expression arrays,the extracted RNA underwent conversion into digital *** percentile shift method facilitated data processing,with the identiﬁcation of genes manifesting signiﬁcant differences accomplished through the application of the ***,a comprehensive analysis involving Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway was conducted on the differentially expressed genes(DEGs).Leveraging the ESTIMATE algorithm,gene signatures were utilized to compute risk scores for gene expression *** vector machine analysis and gene enrichment scores were instrumental in establishing correlations between biomarkers and macrophages,followed by an evaluation of the predictive power of the identiﬁed ***:The functional and pathway associations of the DEGs predominantly centered around G protein-coupled receptors.A noteworthy positive correlation emerged between the blue module,consisting of 416 genes,and the ***4,identiﬁed through support vector machine analysis among intersecting genes,indicated a robust interaction with macrophages,suggesting its potential as a robust ***4 exhibited commendable predictive efﬁcacy,with BP infection inducing its expression in both macrophages and mouse lung *** blotting in macrophages conﬁrmed a signiﬁcant upregulation of FZD4 expression from 0.5 to 24 h *** mouse lung tissue,FZD4 manifested higher expression in the cytoplasm of pulmonary epithelial cells in BP-infected lungs than in the

关键词： Burkholderia pseudomallei Microarray assay Machine learning Bioinformatics FZD4

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Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice

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Current Medical Science 2024年第1期44卷 110-120页

作者： Chang-zhi ZHOU Xiong XIONG Wei-jun TAN Ya-fei WANG Zhen YANG Xue-ying LI Xiu-wen YANG Xiao-fan LIU Sun-feng YU Liang-chao WANG Shuang GENG department of Respiratory and critical care medicine The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014China department of general Surgery Wuhan Wuchang HospitalWuhan University of Science and TechnologyWuhan 430063China

Objective The function of Bcl-6 in T follicular helper(Tfh)cell maturation is indispensable,and Tfh cells play a pivotal role in *** study investigated the impact of Bcl-6 on asthmatic *** The microscopic pathological alterations,airway resistance(AR),and lung compliance(LC)were determined in asthmatic mice and Bcl-6 interference *** surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry,RT-qPCR,and Western blotting,*** relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells(PBMCs)and bronchoalveolar lavage fluid(BALF)were *** Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone(DXM).Asthmatic mice exhibited an increased AR and a decreased LC,while Bcl-6 siRNA or DXM mitigated these *** percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice,and they significantly decreased after Bcl-6 inhibition or DXM ***-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice,and it decreased following Bcl-6 inhibition or DXM *** IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar *** asthmatic mice,the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF,but not with the IgG1 *** The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression,which effectively hinders Tfh cell differentiation,ultimately resulting in a concurrent reduction in IgE production.

关键词： Bcl-6 Tfh asthma airway hyper-responsiveness mouse model

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Serum procalcitonin levels are associated with rhabdomyolysis following exertional heatstroke: an over 10-year intensive care survey

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World Journal of Emergency medicine 2024年第1期15卷 23-27页

作者： Li Zhong Feifei Shuai Conglin Wang Lipeng Han Zhifeng Liu Ming Wu department of Traditional Chinese medicine the First Affi liated HospitalGuizhou University of Chinese MedicineGuiyang 550001China department of Medical critical care medicine General Hospital of Southern Theatre Command of People’s Liberation ArmyGuangzhou 510010China department of Infection and critical care medicine Shenzhen Second People’s Hospital&First Affi liated Hospital of Shenzhen UniversityHealth Science CenterShenzhen 518035China department of Nosocomial Infection Prevention and Control Shenzhen Second People’s HospitalShenzhen 518035China Key Laboratory of Hot Zone Trauma care and Tissue Repair of People's Liberation Army General Hospital of Southern Theatre Command of People's Liberation ArmyGuangzhou 510010China

BACKGROUND:Heatstroke has become a common emergency event in ***(PCT)is used as a biomarker of infection in the emergency department(ED),but its role in rhabdomyolysis(RM)following exertional heatstroke(EHS)remains ***:A retrospective cohort study enrolled patients with EHS from the intensive care unit(ICU).We collected RM biomarkers,inflammation markers,critical disease scores at admission,24 h,48 h,and discharge,and 90-day *** analysis,linear regression and curve fi tting were used to identify the relationship between PCT and ***:A total of 162 patients were recruited and divided into RM(n=56)and non-RM(n=106)*** was positively correlated with myoglobin(Mb),acute hepatic injury,disseminated intravascular coagulation(DIC),Sequential Organ Failure Assessment(SOFA)score,and Acute Physiology and Chronic Health Evaluation II(APACHE II)score,with correlation coefficients of 0.214,0.237,0.285,0.454,and 0.368,respectively(all Pcritically ill *** PCT concentrations should be interpreted cautiously in patients with EHS in the ED.

关键词： Procalcitonin Myoglobin Rhabdomyolysis Exertional heatstroke

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Outcomes of early versus late irrigation and debridement of pediatric open long bone fractures

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World Journal of Orthopedics 2024年第6期15卷 539-546页

作者： Riya Savla Yen-Hong Kuo Nasim Ahmed department of Surgery and Trauma Hackensack Meridian School of MedicineNutleyNJ 07110United States department of Medical Sciences Hackensack Meridian School of medicineNutleyNJ 08753United States Office of Research Administration Hackensack Meridian Health Research InstituteNutleyNJ 077110United States department of Surgery Department of Trauma and Surgical Critical CareJersey Shore University Medical CenterNeptuneNJ 07754United States department of Surgery Department of Trauma and Surgical Critical CareHackensack Meridian School of MedicineNutleyNJ 07110United States

BACKGROUND Open long bone fractures are a major concern for pediatric patients due to the risk of surgical site infection(SSI).Early studies have recommended irrigation and debridement of open fractures within 6 hours-8 hours for the prevention of *** to the American College of Surgeons(ACS)Best Practice Guidelines,in 2015,irrigation and debridement should be done within 24 *** To identify whether early irrigation and debridement,within 8 hours,vs late,between 8 hours and 24 hours,for pediatric open long bone fractures impacts rate of *** Using retrospective data review from the National Trauma Data Bank,Trauma Quality Improvement Project(TQIP)of *** database is own by the ACS and it is the largest database for trauma quality program in the *** matching analysis was performed for the *** There were 390 pediatric patients with open long bone fractures who were incl-uded in the *** completing propensity score matching,we had 176 patients in each category,irrigation and debridement within 8 hours and irrigation and debridement between 8 hours and 24 *** found no significant differences between each group for the rate of deep SSI which was 0.6%for patients who received surgical irrigation and debridement within 8 hours and 1.1%for those who received it after 8 hours[adjusted odd ratio(AOR):0.5,95%CI:0.268-30.909,P>0.99].For the secondary outcomes studied,in terms of length of hospital stay,patients who received irrigation and debridement within 8 hours stayed for an average of 3.5 days,and those who received it after 8 hours stayed for an average of 3 days,with no significant difference found,and there were also no sig-nificant differences found between the discharge dispositions of the *** Our findings support the recommendation for managing open long bone fractures from the ACS:Complete surgical irrigation and debridement within 24 hours.

关键词： Pediatric trauma Open tibia fracture Irrigation and debridement Timing of intervention surgical site infection

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