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Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma

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Current Medical Science 2024年第2期44卷 309-327页

作者： Xiao-jun WANG Jia-ping CHEN Xin-wei QIAO Wang-yang MENG Yang-wei WANG Yun-chong MENG Rong ZHAO Wei LIN Yong-de LIAO Han XIAO Pei-yuan MEI department of thoracic surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China department of thoracic surgery Shandong Provincial Hospital Afiliated to Shandong First Medical UniversityJinan 250021China

Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

关键词： lung squamous cell carcinoma tumorigenesis bone morphogenetic protein GDF10 tumor immune microenvironment

The diagnostic value of tenascin-C in acute aortic syndrome

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Journal of Geriatric cardiology 2024年第3期21卷 359-368页

作者： Ming MA Wei CHEN Hai-Long CAO Jun PAN Qing ZHOU Xin-Long TANG Dong-Jin WANG department of thoracic and cardiovascular surgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingChina department of thoracic and cardiovascular surgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingChina department of thoracic surgery Kunshan Hospital of Traditional Chinese MedicineJiangsuChina

OBJECTIVES Misdiagnosis of acute aortic syndrome(AAS)significantly increases mortality.Tenascin-C(TN-C)is an extracellular matrix glycoprotein related to cardiovascular injury.The elevation of TN-C in AAS and whether it can discriminate suddenonset of acute chest pain in Chinese remains unclear.METHODS We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back pain.Measures to discriminate AAS from acute coronary syndrome(ACS)were compared and calculated.RESULTS From October 2016 to September 2021,376 undiagnosed patients with chest or back pain were enrolled.166 of them were finally diagnosed as AAS,100 were ACS and 110 without cardiovascular diseases(NCV).TN-C was significantly elevated in AAS at 18.18 ng/mL(IQR:13.10–27.68)compared with 7.51 ng/mL(IQR:5.67–11.38)in ACS(P<0.001)and 3.68 ng/mL(IQR:2.50–5.29)in NCV(P<0.001).There was no significant difference in TN-C level among the subtypes of AAS.Of the 166 AAS patients,the peaked level of TN-C was at acute stage(P=0.012),then a slight of decrease was observed at subacute stage.The area under receiver operating characteristic curve for AAS patients versus NCV was 0.979(95%CI:0.964-0.994)for TN-C.At a cutoff level of 11.474 ng/mL,TN-C has a sensitivity of 76.0%,specificity of 85.5%,accuracy of 82.0%,positive predictive value(PPV)of 76.0%,negative predictive value(NPV)of 85.5%.Diagnostic performance of TN-C was superior to D-dimer and hs-cTnT.CONCLUSIONS The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and NCV.TN-C could be a new biomarker to distinguish AAS patients in the early stage after symptoms onset from other pain diseases.

关键词： acute cardiovascular elevated

Identification of tumor-suppressor genes in lung squamous cell carcinoma through integrated bioinformatics analyses

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Oncology Research 2024年第1期32卷 187-197页

作者： HENG LI YOUMING LEI GAOFENG LI YUNCHAO HUANG The 2nd department of thoracic surgery The Third Affiliated Hospital of Kunming Medical UniversityYunnan Tumor HospitalKunming650118China The 1st department of thoracic surgery The Third Affiliated Hospital of Kunming Medical UniversityYunnan Tumor HospitalKunming650118China department of Geriatric thoracic surgery The First Affiliated Hospital of Kunming Medical UniversityKunming650032China

Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management.In this study,we aim to identify a panel of signature genes closely associated with LUSC,which can provide novel insights into the progression of LUSC.Gene expression profiles were retrieved from public resources including gene expression omnibus(GEO)and the cancer genome atlas(TCGA)database.Differentially expressed genes(DEGs)between LUSC specimens and normal lung tissues were identified by bioinformatics analyses.A total of 66 DEGs were identified based on two cohorts of data.CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN,ABI3BP,MAMDC2,FGF7,FAM107A,SPARCL1,DCN,COL14A1,and MFAP4 and CHRDL1,which showed significant downregulation in LUSC.Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment.Together,our data revealed novel candidate tumor-suppressor genes in LUSC,suggesting previously unappreciated mechanisms in the progression of LUSC.

关键词： LUSC DEGs WGCNA PPI network Tumor-suppressor

Systematic analysis of DNA polymerases as therapeutic targets in pan-cancers

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BIOCELL 2024年第1期48卷 123-138页

作者： ZHENHUA LI HUILAI LV FAN ZHANG ZIMING ZHU QIANG GUO MINGBO WANG CHAO HUANG LIJUAN CHEN WENPAN ZHANG YUN LI ZIQIANG TIAN department of thoracic surgery Fourth Hospital of Hebei Medical UniversityShijiazhuang050011China department of thoracic surgery The First Hospital of XingtaiXingtai054001China department of thoracic surgery Affiliated Hospital of Hebei UniversityBaoding050017China Shanghai OrigiMed Co. Ltd.Shanghai200000China department of thoracic surgery The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Introduction:DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis.However,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well understood.Methods:We conducted a systematic analysis using TCGA Pan-Cancer Atlas data and Gene Set Cancer Analysis results to examine the expression profiles of 15 DNA polymerases(POLYs)and their clinical correlations.We also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time(OS)using Kaplan-Meier survival curves.Additionally,we investigated the correlations between POLY expression and immune cells,DNA damage repair(DDR)pathways,and ubiquitination.Drug sensitivity analysis was performed to assess the relationship between POLY expression and drug response.Results:Our analysis revealed that 14 out of 15 POLYs exhibited significantly distinct expression patterns between tumor and normal samples across most cancer types,except for DNA nucleotidylexotransferase(DNTT).Specifically,POLD1 and POLE showed elevated expression in almost all cancers,while POLQ exhibited high expression levels in all cancer types.Some POLYs showed heightened expression in specific cancer subtypes,while others exhibited low expression.Kaplan-Meier survival curves demonstrated significant prognostic value of POLYs in multiple cancers,including PAAD,KIRC,and ACC.Cox analysis further validated these findings.Alteration patterns of POLYs varied significantly among different cancer types and were associated with poorer survival outcomes.Significant correlations were observed between the expression of POLY members and immune cells,DDR pathways,and ubiquitination.Drug sensitivity analysis indicated an inverse relationship between POLY expression and drug response.Conclusion:Our comprehensive study highlights the significant role of POLYs in cancer development and identifies them as promising prognostic and immunological biomarkers for various cancer type

关键词： DNA polymerases(POLYs) Prognostic biomarker The Cancer Genome Atlas(TCGA) Ubiquitination network

Hyperacute experimental model of rat lung transplantation using a coronary shunt cannula

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World Journal of Transplantation 2024年第2期14卷 155-161页

作者： Munehisa Takata Yusuke Tanaka Daisuke Saito Shuhei Yoshida Isao Matsumoto department of thoracic surgery Kanazawa UniversityKanazawa 920-8641IshikawaJapan

BACKGROUND Lung transplantation is a well-established treatment of end-stage lung disease.A rodent model is an inexpensive way to collect biological data from a living model after lung transplantation.However,mastering the surgical technique takes time owing to the small organ size.AIM To conduct rat lung transplantation using a shunt cannula(SC)or modified cannula(MC)and assess their efficacy.METHODS Rat lung transplantation was performed in 11 animals in the SC group and 12 in the MC group.We devised a method of rat lung transplantation using a coronary SC for coronary artery bypass surgery as an anastomosis of pulmonary arteri-ovenous vessels and bronchioles.The same surgeon performed all surgical proce-dures in the donor and recipient rats without using a magnifying glass.The success rate of lung transplantation,operating time,and PaO2 values were com-pared after 2-h reperfusion after transplantation.RESULTS Ten and 12 lungs were successfully transplanted in the SC and MC groups,respectively.In the SC group,one animal had cardiac arrest within 1 h after reperfusion owing to bleeding during pulmonary vein anastomosis.The opera-ting time for the removal of the heart-lung block from the donor and preparation of the left lung graft was 26.8±2.3 and 25.7±1.3 min in the SC and MC groups,respectively(P=0.21).The time required for left lung transplantation in the recipients was 37.5±2.8 min and 35.9±1.4 min in the SC and MC groups,respectively(P=0.12).PaO2 values at 2 h after reperfusion were 456.2±25.5 and INTRODUCTION Lung transplantation is a well-established treatment of end-stage lung disease.Many immune and non-immune mech-anisms in lung transplantation are highly complex,and post-transplant complications such as infections and primary and chronic lung allograft dysfunction must be reduced to improve survival.Therefore,there is a need for immunological and pathophysiological analyses using animal lung transplantation models.The rat lung transplantation model was first reported in 1971[1],followed by the Mizuta

关键词： Lung transplantation Rat Shunt cannula Modified cannula Reperfusion

KLF4 Inhibits the Activation of Human Hepatic Stellate Cell In Vitro

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Current Medical Science 2024年第3期44卷 512-518页

作者： Xing-yu YANG Zhe CHEN Jun TAN Yin-kai XUE Hai ZHENG department of Emergency surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China department of thoracic surgery The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an710061China department of thoracic surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Objective Hepatic stellate cells(HSCs)play a crucial role in liver fibrosis.Early-stage liver fibrosis is reversible and intimately associated with the state of HSCs.Kruppel-like factor 4(KLF4)plays a pivotal role in a wide array of physiological and pathological processes.This study aimed to investigate the effect of KLF4 on the proliferation,apoptosis and phenotype of quiescent HSCs Methods We designed a KLF4 lentiviral vector and a KLF4 siRNA lentiviral vector,to upregulate and silence KLF4 expression in human HSC LX-2 cells via transfection.Cell proliferation was assessed using the CCK-8 assay.Flow cytometry was used to detect the cell cycle distribution and apoptosis rate.Western blotting was used to determine the levels of some quiescence and activation markers of HSCs Results Overexpression of KLF4 significantly increased the levels of E-cadherin and ZO-1,which are quiescent HSC markers,while significantly decreased the levels of N-cadherin and a-SMA,known activated HSC markers.In contrast,cell proliferation and apoptosis rates were elevated in LX-2 cells in which KLF4 expression was silenced Conclusion KLF4 inhibits the proliferation and activation of human LX-2 HSCs.It might be a key regulatory protein in the maintenance of HSC quiescence and may serve as a target for the inhibition of hepatic fibrosis.

关键词： Kruppel-like factor 4 hepatic stellate cells LX-2 cells liver fibrosis

Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer:A metaanalysis

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 214-233页

作者： Mao-Xiu Yuan Qi-Gui Cai Zhen-Yang Zhang Jian-Zhong Zhou Cai-Yun Lan Jiang-Bo Lin The Graduate School Fujian Medical UniversityFuzhou 350000Fujian ProvinceChina department of thoracic surgery Affiliated Hospital of Jinggangshan UniversityJi’an 343000Jiangxi ProvinceChina department of thoracic surgery Fujian Medical University Union HospitalFuzhou 350000Fujian ProvinceChina

BACKGROUND The effectiveness of neoadjuvant therapy in esophageal cancer(EC)treatment is still a subject of debate.AIM To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy(nCRT)and neoadjuvant chemotherapy(nCT)for locally advanced EC(LAEC).METHODS A comprehensive search was conducted using multiple databases,including PubMed,EMBASE,MEDLINE,Science Direct,The Cochrane Library,China National Knowledge Infrastructure,Wanfang Database,Chinese Science and Technology Journal Database,and Chinese Biomedical Literature Database Article.Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected.RESULTS The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival.The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate(OSR)[odds ratio(OR)=0.95],complete response rate(OR=3.15),and R0 clearance rate(CR)(OR=2.25).However,nCT demonstrated a better 5-year OSR(OR=1.02)than nCRT.Moreover,when compared to nCRT,nCT showed reduced risks of cardiac complications(OR=1.15)and pulmonary complications(OR=1.30).CONCLUSION Overall,both nCRT and nCT were effective in terms of survival outcomes for LAEC.However,nCT exhibited better performance in terms of postoperative complications.

关键词： Esophageal cancer Neoadjuvant chemoradiotherapy Radical resection for esophageal cancer Neoadjuvant chemotherapy Meta-analysis

Spontaneous coronary artery rupture after lung cancer surgery:A case report and review of literature

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World Journal of cardiology 2024年第2期16卷 92-97页

作者： Ying-Ding Ruan Jian-Wei Han department of thoracic surgery The First People's Hospital of JiandeJiande 311600Zhejiang ProvinceChina

BACKGROUND Spontaneous coronary artery rupture(SCAR)is a rare and life-threatening complication after lung cancer surgery.We present a case of SCAR following left upper lobectomy,successfully managed through emergency thoracotomy and coronary artery ligation.CASE SUMMARY A 61-year-old male patient underwent left upper lobectomy and mediastinal lymph node dissection for lung cancer.The surgery was performed using singleport video-assisted thoracoscopic surgery,and there were no observed complications during the procedure.However,19 h after surgery,the patient experienced chest discomfort and subsequently developed severe symptoms,including nausea,vomiting,and a drop in blood pressure.Urgent measures were taken,leading to the diagnosis of SCAR.The patient underwent emergency thoracotomy and coronary artery ligation,successfully stopping the bleeding and stabilizing the condition.Despite postoperative complications,the patient made a successful recovery and was discharged from the hospital.CONCLUSION SCAR is a rare but life-threatening complication following lung cancer surgery.Immediate thoracotomy has been shown to be a life-saving measure,while stenting is not the preferred initial approach.

关键词： Spontaneous coronary artery rupture Lung cancer surgery Case report

A prognosis model for predicting immunotherapy response of esophageal cancer based on oxidative stress-related signatures

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Oncology Research 2024年第1期32卷 199-212页

作者： JING GUO CHANGYONG TONG JIANGUANG SHI XINJIAN LI XUEQIN CHEN department of thoracic surgery The First Affiliated Hospital of Ningbo UniversityNingboChina department of Chinese Traditional Medicine The First Affiliated Hospital of Ningbo UniversityNingboChina

Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.

关键词： Esophageal carcinoma OS Prognosis Risk markers Immune cell infiltration