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Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in chinese Patients with Early Breast Cancer:A Single-Institution Study

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Biomedical and Environmental Sciences 2024年第5期37卷 457-470页

作者： KONG Zi Qing LIU Li Qun HUANG De Qin WANG Yu Tong LI Jing Jie ZHANG Zheng WANG Xi Xi LIU Chuan Ling ZHANG Ya Di SHAO Jia Kang ZHU Yi Min CHEN Yi Meng LIU Mei ZHAO Wei Hong Medical School of chinese pla Beijing 100853China department of Medical Oncology the First Medical CenterGeneral Hospital of the Chinese People’s Liberation ArmyBeijing 100853China Nankai University School of Medicine Tianjin 300071China department of Medical Oncology the Fifth Medical CenterGeneral Hospital of the Chinese People’s Liberation ArmyBeijing 100039China department of Medical Oncology Xi'an Jiaotong UniversityXi’an 710061ShaanxiChina department of Pathology the Sixth Medical CenterGeneral Hospital of the Chinese People’s Liberation ArmyBeijing 100037China

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 *** Patients diagnosed with HER2-negative BC(N=999)at our institution between January2011 and December 2015 formed our study *** characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were ***-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low *** HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszelχ^(2)test,P<0.001,Pearson’s R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative *** were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%.Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

关键词： HER2 HER2-low Breast cancer Estrogen receptor Trastuzumab deruxtecan

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Characterization of SH3GLB1 in the Checkfor auditory system and its potential role in updates mitophagy

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Genes & Diseases 2024年第4期11卷 61-64页

作者： Xue Gao Weiqian Wang Jincao Xu Shasha Huang Kun Yang Jinyuan Yang Yijin Chen Guojian Wang Mingyu Han Zhendong Wang Dongyang Kang Yongyi Yuan Pu Dai College of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijing 100853China National Clinical Research Center for Otolaryngologic Diseases State Key Lab of Hearing ScienceMinistry of EducationBeijing 100853China Beijing Key Lab of Hearing Impairment Prevention and Treatment Chinese PLA Medical SchoolBeijing 100853China department of Otolaryngology PLA Rocket Force Characteristic Medical CenterBeijing 100088China

Mitochondria energize the inner ear to maintain the cochlear potential createdbythe striavascularis,assist the motility of outer hair cells,perform synaptic processes,and maintain the spontaneous and sound-driven discharges of the spiral ganglion neurons(SGNs).Mitophagy deficiencies induce the accumulation of damaged organelles and mitochondria in cells and are a primary cause of drug-induced hearing loss.

关键词： auditory maintain potential

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Treatment patterns and survival outcomes in patients with nonmetastatic early-onset pancreatic cancer

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World Journal of Gastroenterology 2024年第12期30卷 1739-1750页

作者： Le-Tian Zhang Ying Zhang Bi-Yang Cao Chen-Chen Wu Jing Wang Graduate School Chinese PLA Medical SchoolBeijing 100853China department of Radiation Oncology First Medical Center of Chinese PLA General HospitalBeijing 100853China department of Internal Medicine Hospital of University of Science and Technology BeijingBeijing 100083China department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND The incidence of patients with early-onset pancreatic cancer(EOPC;age≤50 years at diagnosis)is on the rise,placing a heavy burden on individuals,families,and *** role of combination therapy including surgery,radiotherapy,and chemotherapy in non-metastatic EOPC is not *** To investigate the treatment patterns and survival outcomes in patients with non-metastatic *** A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated *** survival(OS),disease-free survival,and progression-free survival were estimated using the Kaplan-Meier *** and multivariate analyses with the Cox proportional hazards model were used to identify prognostic *** With a median follow-up time of 34.6 months,the 1-year,2-year,and 3-year OS rates for the entire cohort were 84.3%,51.5%,and 27.6%,*** median OS of patients with localized disease who received surgery alone and adjuvant therapy(AT)were 21.2 months and 28.8 months,respectively(P=0.007).The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy(RCT),surgery after neoadjuvant therapy(NAT),and chemotherapy were 28.5 months,25.6 months,and 14.0 months,respectively(P=0.002).The median OS after regional recurrence were 16.0 months,13.4 months,and 8.9 months in the RCT,chemotherapy,and supportive therapy groups,respectively(P=0.035).Multivariate analysis demonstrated that carbohydrate antigen 19-9 level,pathological grade,T-stage,N-stage,and resection were independent prognostic factors for non-metastatic *** AT improves postoperative survival in localized *** after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

关键词： Pancreatic cancer Early-onset Non-metastatic Multimodal treatment Radiotherapy Overall survival

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Lecithin-cholesterol acyltransferase is a potential tumor suppressor and predictive marker for hepatocellular carcinoma metastasis

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3651-3671页

作者： Yan Li Li-Na Jiang Bo-Kang Zhao Mei-Ling Li Yi-Yun Jiang Yi-Si Liu Shu-Hong Liu Li Zhu Xin Ye Jing-Min Zhao department of Pathology and Hepatology The Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China department of Hepatology Center of Infectious Diseases and Pathogen BiologyThe First Hospital of Jilin UniversityChangchun 130061Jilin ProvinceChina First department of Liver Disease Center Beijing Youan HospitalCapital Medical UniversityBeijing 100069China Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100190China department of Pathology The Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China

BACKGROUND Hepatocellular carcinoma(HCC)is a major cause of cancer mortality worldwide,and metastasis is the main cause of early recurrence and poor ***,the mechanism of metastasis remains poorly *** To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC *** The candidate molecule lecithin-cholesterol acyltransferase(LCAT)was screened by gene microarray and bioinformatics *** expression levels of LCAT in clinical cohort samples was detected by quantitative realtime polymerase chain reaction and western *** proliferation,migration,invasion and tumor-forming ability were measured by Cell Counting Kit-8,Transwell cell migration,invasion,and clonal formation assays,*** formation was detected in nude mice after LCAT gene knockdown or *** immunohistochemistry for Ki67,E-cadherin,N-cadherin,matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on *** set enrichment analysis(GSEA)on various gene signatures were analyzed with GSEA version *** machine-learning algorithms(random forest,support vector machine,and logistic regression)were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO *** LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC *** was significantly downregulated in HCC tissues,which is correlated with recurrence,metastasis and poor outcome of HCC *** analysis indicated that LCAT inhibited HCC cell proliferation,migration and invasion both in vitro and in *** data showed that LCAT was negatively associated with HCC size and metastasis(HCC size≤3 cm vs 3-9 cm,P9 cm,P<0.01;metastatic-free HCC vs extrahepatic metastatic HCC,P<0.05).LCAT suppressed the growth,migration and invasion of HCC cell lines via PI3K/A

关键词： Lecithin-cholesterol acyltransferase Tumor suppressor gene Hepatocellular carcinoma PI3K/AKT/mTOR Predicting model

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Development of a diagnostic nomogram for alpha-fetoproteinnegative hepatocellular carcinoma based on serological biomarkers

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2463-2475页

作者： Li He Cui Zhang Lan-Lan Liu Li-Ping Huang Wen-Jing Lu Yuan-Yuan Zhang De-Yong Zou Yu-Fei Wang Qing Zhang Xiao-Li Yang School of Clinical Medicine Weifang Medical UniversityWeifang 261053Shandong ProvinceChina department of Organ Transplantation The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China department of Laboratory Medicine The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China department of Laboratory Medicine Jingyu County People’s HospitalBaishan 135200Jilin ProvinceChina School of Laboratory Medicine Weifang Medical UniversityWeifang 261053Shandong ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related death *** biomarkers play an important role in the early diagnosis and prognosis of *** a certain percentage of HCC patients are negative for alpha-fetoprotein(AFP),the diagnosis of AFP-negative HCC is essential to improve the detection rate of *** To establish an effective model for diagnosing AFP-negative HCC based on serum tumour *** A total of 180 HCC patients were enrolled in this *** expression levels of GP73,des-γ-carboxyprothrombin(DCP),CK18-M65,and CK18-M30 were detected by a fully automated chemiluminescence *** variables were selected by logistic regression *** models were constructed using stepwise backward logistic *** performance of the models was compared using the C statistic,integrated discrimination improvement,net reclassification improvement,and calibration *** clinical utility of the nomogram was assessed using decision curve analysis(DCA).RESULTS The results showed that the expression levels of GP73,DCP,CK18-M65,and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls(P<0.001).Multivariate logistic regression analysis revealed that GP73,DCP,and CK18-M65 were independent factors for diagnosing AFP-negative *** comparing the diagnostic performance of multiple models,we included GP73 and CK18-M65 as the model variables,and the model had good discrimination ability(area under the curve=0.946)and good goodness of *** DCA curves indicated the good clinical utility of the *** Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative *** diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.

关键词： Hepatocellular carcinoma Alpha-fetoprotein-negative Diagnostic Nomogram Biomarker

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Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第21期30卷 2763-2776页

作者： Li He Wan-Sheng Ji Hai-Long Jin Wen-Jing Lu Yuan-Yuan Zhang Hua-Guang Wang Yu-Yu Liu Shuang Qiu Meng Xu Zi-Peng Lei Qian Zheng Xiao-Li Yang Qing Zhang department of Organ Transplantation The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China School of Clinical Medicine Shandong Second Medical UniversityWeifang 261053Shandong ProvinceChina Clinical Research Center The Affiliated Hospital of Shandong Second Medical UniversityWeifang 261053Shandong ProvinceChina department of Laboratory Medicine The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China Physiatry department Naval Aviation UniversityYantai 100071Shandong ProvinceChina

BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver *** To develop a model for predicting prognosis after LT in patients with *** Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and *** expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence *** best cutoff value of biomarkers was determined using the Youden *** regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest *** evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the *** The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after *** nomogram had a higher predictive accuracy than the Milan,University of California,San Francisco,and Hangzhou *** calibration curve analyses indicated a good *** survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical *** The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after *** can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.

关键词： Hepatocellular carcinoma Liver transplantation Liver cancer Nomogram Prognosis

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Early and minimal changes in serum creatinine can predict prognosis in elderly patients receiving invasive mechanical ventilation:A retrospective observational study

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Journal of Intensive Medicine 2024年第3期4卷 368-375页

作者： Qinglin Li Guanggang Li Dawei Li Yan Chen Feihu Zhou department of Critical Care Medicine The First Medical CenterChinese PLA General HospitalBeijingChina department of Critical Care Medicine The Seventh Medical CenterChinese PLA General HospitalBeijingChina department of Critical Care Medicine The Sixth Medical CenterChinese PLA General HospitalBeijingChina department of Anesthesiology The First Medical CenterChinese PLA General HospitalBeijingChina Medical Engineering Laboratory of chinese pla general hospital BeijingChina

BackgroundEmerging evidence suggests that minimal acute kidney injury (stage 1 AKI) is associated with increased hospital mortality rates. However, for those who do not meet the AKI diagnostic criteria, whether a small increase in serum creatinine (SCr) levels is associated with an increased mortality rate in elderly patients is not known. Therefore, we aimed to investigate small elevations in SCr of general conditions and clinical characteristics were compared between the six groups. Prognostic survival factors were identified using Cox regression analysis. Kaplan–Meier survival analysis was employed for the accumulative survival *** total of 1292 patients (1171 men) with a median age of 89 (interquartile range: 85–92) with MV were suitable for further analysis. In all, 376 patients had any stage of early AKI, and 916 patients had no AKI. Among 916 non-AKI patients, 349 patients were in the ratio <10%, 291 in the 10%–<20% group, 169 in the 20%–<30% group, 68 in the 30%–<40% group, 25 in the 40%–<50% group, and 14 in the ≥50% group. The 28-day mortality rates in the six groups from the lowest (<10%) to the highest (≥50%) were 8.0%, 16.8%, 28.4%, 54.4%, 80.0%, and 85.7%, respectively. In the multivariable-adjusted a

关键词： Mechanical ventilation Aged Mortality Ratio △SCr

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Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

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Neural Regeneration Research 2024年第4期19卷 872-880页

作者： Mou Gao Qin Dong Zhijun Yang Dan Zou Yajuan Han Zhanfeng Chen Ruxiang Xu department of Neurosurgery Sichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of China department of Neurosurgery Chinese PLA General Hospital Zhongsai Stem Cell Genetic Engineering Co. Ltd. department of Neurology Fu Xing HospitalCapital Medical University

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head *** previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell ***,the neural regeneration efficiency of induced neural stem cells remains *** this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem *** found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem ***,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived *** predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem *** H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 ***,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem ***,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury *** results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

关键词： closed head injury Ctbp2 induced neural stem cell lncRNA H19 miR-325-3p neurogenesis

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Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2060-2073页

作者： Jing Zhou Mei-Ying Zhang Ai-Ai Gao Cheng Zhu Tao He James G Herman Ming-Zhou Guo School of Medicine NanKai UniversityTianjin 300071China department of Gastroenterology and Hepatology The First Medical CenterChinese PLA General HospitalBeijing 100853China departments of Pathology Characteristic Medical Center of The Chinese People’s Armed Police ForceTianjin 300162China The Hillman Cancer Center University of Pittsburgh Cancer InstitutePittsburghPA 15213United States National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100853China

BACKGROUND Targeting DNA damage response(DDR)pathway is a cutting-edge *** has been reported that Schlafen-11(SLFN11)contributes to increase chemosensitivity by participating in ***,the detailed mechanism is *** To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 *** To reach the purpose,eight esophageal squamous carcinoma cell lines,142 esophageal dysplasia(ED)and 1007 primary esophageal squamous cell carcinoma(ESCC)samples and various techniques were utilized,including methylationspecific polymerase chain reaction,CRISPR/Cas9 technique,Western blot,colony formation assay,and xenograft mouse *** Methylation of SLFN11 was exhibited in 9.15%of(13/142)ED and 25.62%of primary(258/1007)ESCC cases,and its expression was regulated by promoter region ***11 methylation was significantly associated with tumor differentiation and tumor size(both Pplatin,SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways,while inhibiting the ATM/CHK2 signaling *** silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor(AZD0156),both in vitro and in *** SLFN11 is frequently methylated in human *** of SLFN11 is sensitive marker of ATM inhibitor in ESCC.

关键词： Schlafen-11 Esophageal squamous cell carcinoma DNA methylation Synthetic lethality AZD0156

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The new criteria for differential diagnosis of indeterminate biliary stricture under super minimally invasive peroral cholangioscopy

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chinese Medical Journal 2024年第3期137卷 255-256页

作者： Wengang Zhang Ningli Chai Qingzhen Wu Enqiang Linghu department of Gastroenterology Chinese PLA General HospitalBeijing 100853China

Indeterminate biliary stricture(IBS)refers to biliary stricture with an uncertain histological diagnosis^([1])and can be classified as non-neoplastic stricture or neoplastic *** former is mainly caused by various inflammatory biliopancreatic diseases,congenital malformations,or postoperative bile duct injury,while the latter exists in neoplastic lesions such as cholangiocarcinoma,invasion from pancreatic cancer,and adenomas in the bile *** non-neoplastic strictures can be relieved by endoscopic or conservative medical treatment,and only a few require surgical ***,radical surgery or palliative biliary drainage should be applied for neoplastic strictures according to the progression of the ***,it is essential to obtain an accurate diagnosis for IBS in clinical work.

关键词： diagnosis stricture biliary

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