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The diagnostic value of tenascin-C in acute aortic syndrome

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 ***-C(TN-C)is an extracellular matrix glycoprotein related to cardiovascular *** elevation of TN-C in AAS and whether it can discriminate suddenonset of acute chest pain in Chinese remains *** We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back *** to discriminate AAS from acute coronary syndrome(ACS)were compared and *** 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 *** 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 *** area under receiver operating characteristic curve for AAS patients versus NCV was 0.979(95%CI:0.964-0.994)for *** 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 *** The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and ***-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

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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 ***,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well ***: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 *** also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time(OS)using Kaplan-Meier survival ***,we investigated the correlations between POLY expression and immune cells,DNA damage repair(DDR)pathways,and *** sensitivity analysis was performed to assess the relationship between POLY expression and drug ***: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 *** POLYs showed heightened expression in specific cancer subtypes,while others exhibited low ***-Meier survival curves demonstrated significant prognostic value of POLYs in multiple cancers,including PAAD,KIRC,and *** analysis further validated these *** patterns of POLYs varied significantly among different cancer types and were associated with poorer survival *** correlations were observed between the expression of POLY members and immune cells,DDR pathways,and *** sensitivity analysis indicated an inverse relationship between POLY expression and drug ***:Our comprehensive study highlights the significant role of POLYs in cancer development and identifies them as promising prognostic and

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

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Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

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Journal of Pharmaceutical Analysis 2024年第2期14卷 196-210页

作者： Mariola Olkowicz Khaled Ramadan Hernando Rosales-Solano Miao Yu Aizhou Wang Marcelo Cypel Janusz Pawliszyn department of Chemistry University of WaterlooWaterlooONCanada Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian UniversityKrakowPoland Latner thoracic surgery Research Laboratories Toronto General Hospital Research InstituteUniversity Health NetworkTorontoONCanada The Jackson Laboratory JAX Genomic MedicineFarmingtonCTUSA Division of thoracic surgery Department of SurgeryUniversity Health NetworkUniversity of TorontoToronto Lung Transplant ProgramTorontoONCanada

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

关键词： Pulmonary metastases Colorectal cancer Adjuvant chemotherapy In vivo lung chemo-perfusion Solid-phase microextraction(SPME)microprobes Spatial metabolomics

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Chronic active and atrophic gastritis as significant contributing factor to the development of gastric cystica profunda

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World Journal of Gastroenterology 2024年第17期30卷 2308-2310页

作者： Veronika Papp Pál Miheller department of surgery Transplantation and GastroenterologySemmelweis UniversityBudapest 1082Hungary

Gastric cystica profunda(GCP)is an uncommon but underestimated gastric *** precancerous potential determines its *** addition to previous mucosa injury due to operations,biopsy or polypectomy,chronic active and atrophic gastritis may also lead to the development of *** carefully examining the stomach and taking biopsy samples from the susceptible regions,the stage of atrophy can be *** atrophic gastritis is a risk factor for cancer evolvement and it can also contribute to GCPs *** frequently occur close to early gastric cancers(EGCs)or EGC can arise from the cystic *** resection is an effective and minimally invasive treat-ment in GCP.

关键词： Gastric cystica profunda Chronic active gastritis Atrophic gastritis Operative Link for Gastritis Assessment staging Early gastric cancer Endoscopic resection

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Tet methylcytosine dioxygenase 2(TET2)deficiency elicits EGFR-TKI(tyrosine kinase inhibitors)resistance in non-small cell lung cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1706-1720页

作者： Jian Zhang Kejia Zhao Wenjing Zhou Ran Kang Shiyou Wei Yueli Shu Cheng Yu Yin Ku Yonghong Mao Hao Luo Juqin Yang Jiandong Mei Qiang Pu Senyi Deng Zhengyu Zha Gang Yuan Shensi Shen Yaohui Chen Lunxu Liu department of thoracic surgery and Institute of thoracic Oncology West China Hospital of Sichuan UniversityChengdu 610097China Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of lung Cancer Sichuan UniversityChengdu 610097China Biobank of West China Hospital Sichuan UniversityChengdu 610041China

Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical *** found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC *** perturbationof TET2 rendered parental cells more tolerant to TKI ***2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI *** or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in *** findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 ***,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

关键词： TET2 TKI resistance

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Neoadjuvant camrelizumab(an anti-PD-1 antibody)plus chemotherapy or apatinib(a VEGFR-2 inhibitor)for initially unresectable stage II–III non-small-cell lung cancer:a multicentre,two-arm,phase 2 exploratory study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3015-3023页

作者： Haoran Xia Han Zhang Zheng Ruan Huibiao Zhang Liangdong Sun Hezhong Chen Yongxin Zhou Lele Zhang Dongliang Bian Xinsheng Zhu Jing Zhang Fenghuan Sun Huansha Yu Nan Song Xiaogang Liu Yuming Zhu Haiping Zhang Wenxin He Jian Chen Jie Yang Guohan Chen Shiliang Xie Dongfang Tang Xiaomiao Zhang Liang Duan Deping Zhao Qinchuan Li Peng Zhang Gening Jiang department of thoracic surgery Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of thoracic surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of thoracic surgery Huadong Hospital Affiliated to Fudan UniversityShanghaiChina department of thoracic surgery Changhai HospitalNaval Medical UniversityShanghaiChina department of thoracic-Cardiovascular surgery Tongji HospitalTongji University School of MedicineShanghaiChina Central Laboratory Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Experimental Animal Center Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of thoracic surgery Shanghai East HospitalTongji University School of MedicineShanghaiChina

This multicentre,two-arm,phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II–III non-small-cell lung cancer(NSCLC).Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks(arm A)or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily(arm B),for 2–4 cycles,followed by *** primary endpoint was major pathological response(MPR)*** patients in arm A and 21 in arm B were *** rates were 50.0%(15/30)in arm A and 42.9%(9/21)in arm B,with all patients achieving R0 *** these patients,the MPR and pathological complete response rates were both 20.0%(95%CI 4.3–48.1)in arm A and were 55.6%(95%CI 21.2–86.3)and 11.1%(95%CI 0.3–48.2)in arm B,*** corresponding objective response rates were 33.3%(95%CI 11.8–61.6)and 55.6%(95%CI 21.2–86.3).With a median follow-up of 22.4 months(95%CI 19.0–26.0),the median event-free survival was not reached(NR;95%CI 13.6-NR)in arm A and 16.8 months(95%CI 8.6-NR)in arm *** 3 or above treatment-related adverse events occurred in eight(26.7%)patients in arm A and three(14.3%)in arm *** analysis showed baseline TYROBP expression was predictive of treatment response in arm *** camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II–III NSCLC.

关键词： surgery chemotherapy treatment

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Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 117-122页

作者： Xin Yang Lu Lu Wen-Wei Zhu Yi-Feng Tao Cong-Huan Shen Jin-Hong Chen Zheng-Xin Wang Lun-Xiu Qin Hepatobiliary surgery and Liver transplantation Centers Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan UniversityShanghai 200040China

Hepatectomy is still the major curative treatment for patients with liver ***,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic *** vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver *** to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver *** efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar ***,the application of ELRA for liver malignances has gained more ***,standardization of clinical practice norms and international consensus are still *** prognostic impact in these oncologic patients also needs further *** this review,we summarized the principles and recent progresses on ELRA.

关键词： Ex vivo liver resection Liver auto-transplantation Oncology Liver malignancies

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Promising prognostic value of ATP binding cassette transporters and their correlation with tumor-infiltrating immune cells in lung adenocarcinoma

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Genes & Diseases 2024年第5期11卷 91-93页

作者： Linzi Wei Qian Yu Xueying Yang department of thoracic surgery The Fourth Affiliated Hospital of China Medical UniversityShenyangLiaoning 110032China

lung cancer(LC)is a prevalent and fatal malignancy,with high incidence and mortality rates.1 ATP binding cassette(ABC)transporters,a superfamily of integral membrane proteins,use ATP hydrolysis to facilitate substrate transport across cellular membranes.2 The pivotal role of ABC transporters in tumorigenesis was initially established by Mochida,3 who demonstrated that the loss of ABCB1 suppresses intestinal polyp formation and tumor progression in *** investigations have reported correlations between ABC transporters and the tumor microenvironment and cancer immunotherapy response,suggesting their modulatory effects on tumor progression and immunotherapy.

关键词： mortality adenocarcinoma lung

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Stem cell technology for antitumor drug loading and delivery in oncology

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Oncology Research 2024年第3期32卷 433-437页

作者： FRANCESCO PETRELLA ENRICO MARIO CASSINA LIDIA LIBRETTI EMANUELE PIRONDINI FEDERICO RAVEGLIA ANTONIO TUORO department of thoracic surgery Fondazione IRCCSS an Gerardo dei TintoriMonza20900Italy

The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic *** stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family *** the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy *** chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options *** some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.

关键词： Mesenchymal stromal cell Drug loading Drug delivery Mesothelioma Melanoma Glioblastoma Pancreatic ductal adenocarcinoma Multiple myeloma

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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 Affiliated to Shandong First Medical UniversityJinan 250021China

Objective:lung squamous cell carcinoma(LUSC)is associated with a low survival *** suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and ***,a comprehensive analysis of their role in LUSC is *** study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of ***:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO ***,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in *** 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 *** specimens were examined by immunohistochemical analysis to confirm the diagnostic value in ***,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 ***: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 ***10 showed a significant positive correlation with immune cell infiltration and immune checkpoint ***: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

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