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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期68卷 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang department of Oncology The Fifth Medical Center of Chinese PLA General Hospital department of thoracic surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteraction<0.001).Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs（P=0.040） and sqNSCLCs（P=0.014）,*** the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNSCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

关键词： non-squamous NSCLC squamous NSCLC LRP1B deleterious mutations predictive biomarker immune checkpoint inhibitor

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Unlocking the future:Mitochondrial genes and neural networks in predicting ovarian cancer prognosis and immunotherapy response

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World Journal of Clinical Oncology 2025年第1期16卷 43-52页

作者： Zhi-Jian Tang Yuan-Ming Pan Wei Li Rui-Qiong Ma Jian-Liu Wang department of Obstetrics and Gynecology Peking University People’s HospitalBeijing 100044China Cancer Research Center Beijing Chest HospitalBeijing 101149China department of thoracic surgery Sichuan Provincial People's HospitalChengdu 610072Sichuan ProvinceChina

BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment *** To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural *** Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression *** genes were sourced from the MitoCarta3.0 *** discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation *** the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were *** In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy *** average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation *** average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation *** The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.

关键词： Ovarian cancer Mitochondria Prognosis Immunotherapy Neural network

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High Serum CEA and CYFRA21-1 Levels after a Two-Cycle Adjuvant Chemotherapy for NSCLC:Possible Poor Prognostic Factors

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Clinical oncology and cancer researeh 2012年第4期9卷 270-273页

作者： Xue-feng Lin Xiao-dong Wang Da-qiang Sun Zhi Li Yue Bai tianjin Medical College department of thoracic surgery Tianjin Chest Hospital

Objective The aim of this study was to test whether carcinoembryonic antigen （CEA） and cytokeratin 19 fragments （CYFRA21-1） can be used as a prognostic factor for non-small-cell lung cancer （NSCLC） after two cycles of adjuvant chemotherapy in NSCLC patients. Methods A total of 169 patients underwent at least two cycles of adjuvant chemotherapy. The serum levels of CEA and CYFRA21-1 were recorded after the second cycle of chemotherapy, and the patient follow-up was conducted. Overall survival （OS） and disease- free survival （DFS） were used as the primary endpoint and the secondary endpoint, respectively. Results The high levels of CEA and CYFRA21-1 after two cycles of adjuvant chemotherapy were poor prognostic factors for OS, with risk ratios （RR） of 2.003 and 1.702, respectively. A high CEA level was a poor prognostic factor （RR 1.152） for DFS. The median survival time （MST） of the high CEA level group was 26 months, whereas that of the normal group was 61 months （P〈0.0001）. The median DFS time of the high CEA group and the normal group was 34 and 53 months, respectively （P〈0.0001）. The MST of the high CYFRA21-1 group and the normal group was 43 and 56 months, respectively （P〈0.0001）. Conclusions The high serum levels of CEA or CYFRA21-1 after two cycles of adjuvant chemotherapy are poor prognostic factors for NSCLC patients.

关键词： non-small-cell lung cancer carcinoembryonic antigen cytokeratin 19 fragement adjuvant chemotherapy prognosis.

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Expression of SKP2 Protein in Lung Carcinoma

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Chinese Journal of Cancer Research 2008年第3期20卷 216-221页

作者：赵君杨春鹿张欢丁卫忠柳致平刘景义 department of thoracic surgery the First Affiliated HospitalChina Medical University Center of Supersound the MCH Hospital of Tanggu District in Tianjin City department of thoracic surgery Shenyang Municipal Thoracic Hospital

Objective： To study the expressive characteristics of SKP2 protein in lung carcinoma and its implication for prognosis. Methods： The expression of SKP2 protein was detected in 89 non small cell lung carcinoma, 13 small cell lung carcinoma, 10 lung benign lesion tissues by Tissue Chip and Immunohistochemistry technology. Results： The positive rate of SKP2 protein staining was （23.52±13.57）% in non small cell lung carcinoma and （53.85±12.26）% in small cell lung carcinoma, which were significantly higher than （2.91±1.27）% in lung benign lesion tissues. It was highest in small cell lung carcinoma and lowest in lung benign lesion tissues, with a significant difference between them （P=0.000）. The expressive level of SKP2 protein in lung carcinoma tissues was closely related to cell differentiation, lymph node metastasis and pathological types, but not to age, sex, smoking history, tumor site and size, and TNM staging. The survival analysis revealed that the 5-year survival rate of lung carcinoma patients was lower in SKP2 protein positive expression group than that in negative expression group （P1=0.003/0.002; r=-0.275, P2=0.005）. Conclusion. The positive expression of SKP2 protein is higher in lung carcinoma than in lung benign lesion tissues, in particular, much higher in small cell lung carcinoma. In lung carcinoma, its expressive level was closely related to cell differentiation, lymph node metastasis and pathological types. Moreover, it may be an independent factor to prognosis of patients with lung carcinoma.

关键词： Lung carcinoma SKP2 protein Tissue Chip Immunohistochemistry

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Left ventricular thrombosis caused cerebral embolism during venoarterial extracorporeal membrane oxygenation support: A case report

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World Journal of Clinical Cases 2024年第5期12卷 973-979页

作者： Yao-Bang Bai Feng Zhao Zhen-Hua Wu Guo-Ning Shi Nan Jiang Intensive Care Unit Department of Cardiac SurgeryTianjin Chest HospitalTianjin 300222China department of Cardiac surgery Tianjin Chest HospitalTianjin 300222China

BACKGROUND Venoarterial(VA)extracorporeal membrane oxygenation(ECMO),an effective short-term circulatory support method for refractory cardiogenic shock,is widely ***,retrospective analyses have shown that VA-ECMO-assisted cases were associated with a relatively high mortality rate of approximately 60%.Embolization in important organs caused by complications of left ventricular thrombosis(LVT)during VA-ECMO is also an important *** the incidence of LVT during VA-ECMO is not high,the consequences of embolization are *** SUMMARY A 37-year-old female patient was admitted to hospital because of fever for 4 d and palpitations for 3 *** excluding the diagnosis of coronary heart disease,we established a diagnosis of“clinically explosive myocarditis”.The patient still had unstable hemodynamics after drug treatment supported by VA-ECMO,with heparin for *** day 4 of ECMO support,a left ventricular thro-mbus attached to the papillary muscle root of the mitral valve was found by transthoracic *** ventricular decompression was performed and ECMO was successfully removed,but the patient eventually died of multiple cerebral *** LVT with high mobility during VA-ECMO may cause embolism in important ***,a"wait and see"strategy should be avoided.

关键词： Venoarterial extracorporeal membrane oxygenation Left ventricular thrombosis Cerebral embolism Magnetic Resonance Imaging Therapy Case report

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Effect and molecular mechanism of mir-146a on proliferation of lung cancer cells by targeting and regulating MIF gene

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Asian Pacific Journal of Tropical Medicine 2016年第8期9卷 783-788页

作者： Wu-Ming Wang Ji-Chun Liu Medical College of Nanchang University department of thoracic surgery Jiangxi Chest Hospital department of thoracic & Cardiovascular surgery the First Affiliated Hospital of Nanchang University

Objective: To discuss the effect and molecular mechanism of mi R-146 a on the proliferation of lung cancer cells by targeting and regulating the macrophage migration inhibitory factor(MIF) gene. Methods: RT-PCR was employed to detect expression of mi R-146a; immunohistochemistry was used to detect the expression of MIF. The luciferase reporter gene technique was adopted to verify that MIF was the specific reverse target gene of mi R-146 a and the liposome LipofectamineTM2000 was employed to transfer the modeled mi R-146 a mimics, and mi R-146 a negative control(NC) in NSCLC cells to detect the expression of MIF m RNA and protein. MTT assay was used to detect cell viability, cloning technique to detect cell proliferation ability, Annexin V-PI to detect cell apoptosis, UV spectrophotometry to detect viability of cysteinyl aspartate specific proteinase 3(Caspase 3), and western blot to detect expression of nuclear factor-κB(NF-κB) in cells. Results: The expression of mi R-146 a in NSCLC lung tissues was lower than that in the normal lung tissues besides the lung cancer; while the expression of mi R-146 a in NSCLC cells was lower than that in normal human embryonic lung tissues. It was chosen as the subsequent cell line for its appropriate expression in A549. The expression of MIF protein in NSCLC lung tissues was higher than that in the normal lung tissues besides the lung cancer. The luciferase reporter gene proved that MIF was the reverse target gene of mi R-146 a. The mi R-146 a mimics were transfected into A549 cells through the liposome. Compared with NC group, the expression of MIF protein and m RNA was significantly decreased(P<0.01), with the decrease in the cell viability(P<0.01), the decrease in the number of clones(P<0.01), cell apoptosis(P<0.01), the increase in the activity of Caspase 3(P<0.01), and decrease in the phosphorylation of NF-κB p65(P<0.01). Conclusions: mi R-146 a has low expression in NSCLC tissues and cell lines, while MIF has the over expres

关键词： MicroRNA-146a Macrophage migration inhibition factor Non-small cell lung cancer Proliferation

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Lymph node dissection in esophageal carcinoma: Minimally invasive esophagectomy vs open surgery

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World Journal of Gastroenterology 2016年第19期22卷 4750-4756页

作者： Bo Ye Chen-Xi Zhong Yu Yang Wen-Tao Fang Teng Mao Chun-Yu Ji Zhi-Gang Li department of thoracic surgery Shanghai Chest Hospital Shanghai Jiao Tong University

AIM: To compare lymph node dissection results of minimally invasive esophagectomy(MIE) and open surgery for esophageal squamous cell ***: We retrospectively reviewed data from patients who underwent MIE or open surgery for esophageal squamous cell carcinoma from January 2011 to September 2014. Number of lymph nodes resected, positive lymph node(p N+) rate, lymph node sampling(LNS) rate and lymph node metastatic(LNM) rate were evaluated. R E S U LT S : A m o n g 4 4 7 p a t i e n t s i n c l u d e d, 1 2 3 underwent MIE and 324 underwent open surgery. The number of lymph nodes resected did not significantly differ between the MIE and open surgery groups(21.1 ± 4.3 vs 20.4 ± 3.8, respectively, P = 0.0944). The p N+ rate of stage T3 esophageal squamous cell carcinoma in the open surgery group was higher than that in the MIE group(16.3% vs 11.4%, P = 0.031), but no differences was observed for stages T1 and T2 esophageal squamous cell carcinoma. The LNS rate at left para-recurrent laryngeal nerve(RLN) site was significantly higher for open surgery than for MIE(80.2% vs 43.9%, P surgery group was significantly higher than that in the MIE group, regardless of pathologic T stage. CONCLUSION: For stages T1 and T2 esophageal squamous cell carcinoma, the lymph node dissection result after MIE was comparable to that achieved by open surgery. However, the efficacy of MIE in lymphadenectomy for stage T3 esophageal squamous cell carcinoma, particularly at left para-RLN site, remains to be improved.

关键词： Esophageal cancer Lymph node Minimally invasive surgery

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CARDIAC　ARRHYTHMIA　AFTER　LUNG　CANCER　surgery　－－ANALYSIS　OF　140　PNEUMONECTTOMY　CASES

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Chinese Journal of Cancer Research 1995年第4期7卷 272-274页

作者：吴怀申周允中张良平张新民陈文虎郑敏 department of thoracic surgery Shanghai Chest Hospital Shanghai

Among 808 surgically resected lung cancer cases at Shanghai chest hospital during 1991 to 1992, 140 of them (17.3%) underwent Pneumonectomy. Of the 140 cases:124 male, 16 female; aged 27-74 yrs, 35.7% elder (60 and over), preoperative abnormal EKG was found in 38 cases, operative mortality was 4.3%. The histopathological diagnosis were: squamous 43.6%, adeno. 36.4%, small cell 8.6%, mixed type 11.4%. The pTNM stages: stage I 2.9%, II 17.1%, IIIa 55.0%, IIIb 21.4%, IV 3.6%.Postoperatively, arrhythmia occuried in 76 cases, with an incidence of 54.3%. Of the 76 arrhythmias, atrial fibrillation was seen in 7 patients, atrial premature beats in 2, supraventricular tachycardia in 1, and sinus tachycardia in 66. The incidences of cadiac arrhythmia during the postoperative day (DO), first day (D1), D2, D3,and D4 were 48.7%, 35.5%, 7.9%, 4.0%and 2.6%respectively. Conclusion: the cardiac arrhythmia is the most common complication after pneumonectomy for lung cancer surgery. The major causes were incisional pain, hypovolemia due to blood loss and respirative insufficiency due to anomia. The perioperative prevention and treatment for arrhythmia were also discussed.

关键词： Lung cancer Pneumonectomy Cardiac arrhythmia,Complication,Morbidity.

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Lactobacillus levels and prognosis of patients with acute myocardial infarction

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Journal of Geriatric Cardiology 2022年第2期19卷 101-114页

作者： Jing-Jing CAI Yin LIU Jie WANG Jing-Xian WANG Yuan WANG Shi-Bo XU Zhuang CUI Jing GAO Graduate School Tianjin Medical UniversityTianjinChina department of Cardiology Xing’anmeng People’s HospitalInner MongoliaChina Clinical School of thoracic Tianjin Medical UniversityTianjinChina department of Cardiology Tianjin Chest HospitalTianjinChina School of Public Health Tianjin Medical UniversityTianjinChina Cardiovascular Institute Tianjin Chest HospitalTianjinChina

OBJECTIVE To explore the relationship between Lactobacillus and prognosis of acute myocardial infarction(AMI)patients treated by percutaneous coronary intervention(PCI)and its correlation with clinical *** Consecutive patients with AMI in the coronary care unit of tianjin chest hospital in China who received emergency PCI between July 2017 and December 2018 were ***’fecal 16 S r DNA gene sequencing data were analyzed and subjects were categorized into low,medium and high level groups according to stool Lactobacillus *** primary endpoints were major adverse cardiac *** regression analysis was used to analyze the relationship between Lactobacillus and *** correlation analysis and trend tests were used to assess the relationship between Lactobacillus and the clinical *** The data of 254 patients were included in the *** age was 65.90±11.56 years,and 152 patients(59.84%)were ***-up time was 652(548.25-753.00)*** Cox regression analysis showed a significantly lower risk of major adverse cardiac events in patients with Lactobacillus>7.1 copies/g[adjusted hazard ratio(HR)=0.216,95%CI:0.094-0.493,P<0.001]compared to patients with Lactobacillus≤3.6 copies/*** significant differences were shown in ST-segment elevation myocardial infarction(STEMI)(HR=0.217,95%CI:0.085-0.551,P=0.001).Lactobacillus was a protective factor for male smokers aged over 60 years whose brain natriuretic peptide was over 1,000 pg/m *** correlation analysis showed that Lactobacillus correlated negatively with white blood cells,neutrophils,high-sensitivity C-reactive protein,Troponin T,creatine kinase,creatine kinase-MB and brain natriuretic peptide(downward trend),and correlated positively with left ventricular ejection fraction(upward trend).CONCLUSIONS This study is the first to reveal the correlation between Lactobacillus and inflammation and myocardial damage after STEMI.

关键词： patients infarction prognosis

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thoracic exploration for the diagnosis of multiple pulmonary vein varices:case report

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Chinese Medical Journal 2007年第22期120卷 2053-2055页

作者： ZHANG Xun HAN Hong-li SHI Zhen-liang department of thoracic surgery Tianjin Chest Hospital Tianjin 300051 China

Pulmonary vein varix, congenital or acquired dilation of the pulmonary vein, is a rare vascular *** disease often presents as a pulmonary mass on chest roentgenography, and pulmonary angiography, computed tomography （CT）, or magnetic resonance imaging （MRI） is considered necessary for diagnosis. The diagnosis of the disease by thoracic exploration is rare because the present case was diagnosed as a pulmonary arteriovenous fistula before operation.

关键词： pulmonary vein varix thoracic exploration diagnosis

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