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Amitriptyline inhibits NLRP3 inflammasome activation via the ASM/CE pathway in a cell model of NAFLD

第二十二届全国中西医结合消化系统疾病学术会议暨消化疾病诊治进展学习班

作者： Jiang Chun-ying,Li Xue-liang,zhang Ai-qing. department of Gastroenterology,the first affiliated hospital of nanjing medical university,nanjing(210029)

Objective The aim of the present study were to assess the distribution of ICC in the colon of patients with slow-transit constipation,and to investigate whether the alteration of ICC in patients with STC is associated...

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BIOCELL 2024年第5期48卷 759-769页

作者： QIN liu CHUNYAN NIU QIANG zhang SHIQIN SUN YUE CHEN YONGQIANG SHI Shengli Clinical medical College Fujian Medical UniversityFuzhou350001China department of Gastroenterology Nanjing Lishui People’s HospitalZhongda Hospital Lishui BranchSoutheast UniversityNanjing211200China department of Gastroenterology Yancheng Third People’s Hospital(The Yancheng School of Clinical Medicine of Nanjing Medical University)Yancheng224000China Administrative department of Teaching and Scientific Research Nanjing Lishui People’s HospitalZhongda Hospital Lishui BranchSoutheast UniversityNanjing211200China

Background:Nonalcoholic fatty liver disease(NAFLD)is a global health concern with the acid sphingomyelinase(ASM)/ceramide(CE)pathway and the NOD-like receptor family,pyrin domain-containing protein 3(NLRP3)inflammasome identified as pivotal players in lipid disorders and *** study explores the interaction mechanism between the ASM/CE pathway and NLRP3 in NAFLD cell models,aiming to understand the impact of amitriptyline(Ami),an ASM inhibitor,on lipid deposition and hepatocyte injury by regulating the ASM/CE-NLRP3 ***:HepG2 and HL-7702 cells were exposed to free fatty acids(FFAs)to establish the NAFLD *** cells were divided into 5 groups:control group,model group,Ami group,tumor necrosis factoralpha(TNF-α)group,and Ami+TNF-α*** lipid droplets were visualized using Oil Red O staining,and Western blot analysis quantified ASM,NLRP3,and caspase 1 protein *** linked immunosorbent assay(ELISA)was measured CE and ASM levels,while qRT-PCR assessed mRNA *** apoptotic rate was evaluated by flow cytometry(FCM).Results:Following FFAs incubation,significant increases in ASM and CE levels were observed in HepG2 and HL-7702 cells,accompanied by elevated expression of NLRP3,and caspase 1,and IL-1β.TNF-αtreatment further amplified these *** demonstrated a reduction in lipid deposition,suppressed ASM/CE pathway activation,downregulated NLRP3 and caspase 1 expression,and improved ***,MCC950,a selective inhibitor of the NLRP3,mitigated NLRP3,caspase 1,and IL-1βexpression,alleviating lipid deposition and apoptosis in the NAFLD cell ***:The ASM/CE-NLRP3 pathway in NAFLD cells promotes hepatocyte steatosis,inflammation,and cell *** emerges as a promising therapeutic agent by inhibiting the ASM/CE-NLRP3 pathway,underscoring its potential as a key target for NAFLD treatment.

关键词： Nonalcoholic fatty liver disease Hepatocyte Amitriptyline ASM/CE pathway NLRP3 Nonalcoholic steatohepatitis

Sintilimab(anti-PD-1 antibody)plus chidamide(histone deacetylase inhibitor)in relapsed or refractory extranodal natural killer T-cell lymphoma(SCENT):a phase Ⅰb/Ⅱ study

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2765-2773页

作者： Yan Gao Haixia He Xueping Li Liling zhang wei Xu Ru Feng Wenyu Li Yin Xiao Xinxiu liu Yu Chen Xiaoxiao wang Bing Bai Huijing Wu Qingqing Cai Zhiming Li Jibin Li Suxia Lin Yanxia He Liqin Ping Cheng Huang Jiaying Mao Xiujin Chen Baitian Zhao Huiqiang Huang State Key Laboratory of Oncology in South China&Collaborative Innovation Center of Cancer Medicine Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouChina department of medical Oncology Sun Yat-sen University Cancer CenterGuangzhouChina department of Radiation Oncology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina department of Hematology Sun Yat-sen University Cancer CenterGuangzhouChina Cancer Center Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and TechnologyWuhanChina department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingChina department of Hematology Nanfang HospitalSouthern Medical UniversityGuangzhouChina department of Lymphoma Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouChina department of pathology Guangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouChina department of medical Oncology Hubei Cancer CenterWuhanChina department of Clinical Research Sun Yat-sen University Cancer CenterGuanzhouChina department of Pathology Sun Yat-sen University Cancer CenterGuangzhouChina

Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma(RR-ENKTL),however,the complete response(CR)rate and the duration of response(DOR)need to be *** phase 1b/2 study investigated the safety and efficacy of sintilimab,a fully human anti-PD-1 antibody,plus chidamide,an oral subtype-selective histone deacetylase inhibitor in 38 patients with *** objective response rate(ORR)of combination treatment was 80%.Patients received escalating doses of chidamide,administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 *** dose-limiting events were observed,RP2D of chidamide was 30 mg twice a ***-nine patients were enrolled in phase *** the intention-to-treat population(n=37),overall response rate was 59.5% with a complete remission rate of 48.6%.The median DOR,progression-free survival(PFS),and overall survival(OS)were 25.3,23.2,and 32.9 months,*** most common grade 3 or higher treatment-emergent adverse events(AEs)were neutropenia(28.9%)and thrombocytopenia(10.5%),immune-related AEs were reported in 18(47.3%)*** biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic ***3 mutation shows an unfavorable *** outcome of anticipate ORR was not achieved,sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first *** is a promising therapeutic option for this population.

关键词： killer lymphoma doses

Prevention of colonic fibrosis by taurine in rats with colitis induced by 2,4,6-trinitrobenzene sulphonic acid

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Prevention of colonic fibrosis by taurine in rats with colit...

Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade

第二十二届全国中西医结合消化系统疾病学术会议暨消化疾病诊治进展学习班

作者： Lin lin,Cheng jiafei,Ning yueji,zhang wei,zhang hongjie department of Gastroenterology,The first affiliated hospital of nanjing medical university,nanjing 210029,P.R.China

Background:Over one-third of patients with Crohn’ s disease(CD) would develop intestinal stricture,with no effective medical intervention,though much adventage has been made during the past several *** has an antifibrotic effect on a number of organs,however, its role in colonic fibrosis remains ***:To investigate the efficacy of taurine on

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2936-2952页

作者： Liang Zhao Yizhen Pang Yangfan Zhou Jianhao Chen Hao Fu wei Guo weizhi Xu Xin Xue Guoqiang Su Long Sun Hua Wu Jingjing zhang Zhanxiang wang Qin Lin Xiaoyuan Chen Haojun Chen department of Nuclear Medicine and Minnan PET Center Xiamen Key Laboratory of RadiopharmaceuticalsThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingaporeSingapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore department of Radiation Oncology Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina department of Colorectal Tumor Surgery Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina department of Cardiothoracic Surgery Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingChina Nanomedicine Translational Research Program NUS Center for NanomedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore department of Neurosurgery and department of Neuroscience Fujian Key Laboratory of Brain Tumors Diagnosis and Precision TreatmentXiamen Key Laboratory of Brain Centerthe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstituteChinese Academy of SciencesXiamenChina

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor *** radionuclide therapy delivers radiation directly to tumor ***1004 is a fibroblast activation protein(FAP)-targeting radiopharmaceutical,conjugated with the albumin binder Evans Blue,which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical ***,we demonstrate that^(68)Ga/^(177)Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor *** therapy with^(177)Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor *** combination of^(177)Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice,with mice showing 100%tumor rejection upon ***,single-cell RNA sequencing(scRNA-seq),and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication,CD8^(+)T-cell activation and expansion,M1 macrophage counts,antitumor activity of neutrophils,and T-cell receptor diversity.A preliminary clinical study demonstrated that^(177)Lu-LNC1004 was well-tolerated and effective in patients with refractory ***,scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade *** was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell *** conclusion,our data supported the efficacy of immunotherapy combined with^(177)Lu-LNC1004 for cancer patients with FAP-positive tumors.

关键词： immunity retention holds

The Relationship between Viral Replication and the Severity of Hepatic Necroinflammatory Damage Changed before HBeAg Loss in Patients with Chronic Hepatitis B Virus Infection

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Journal of Clinical and Translational Hepatology 2024年第4期12卷 381-388页

作者： Leijie wang Jian wang Kunyu Zhao Lina Jiang Xinxin zhang Jingming Zhao Jie Li Fengmin Lu department of Microbiology and Immunology College of Basic Medical SciencesZhengzhou UniversityZhengzhouHenanChina department of Microbiology&Infectious Disease Center School of Basic Medical SciencesPeking UniversityBeijingChina department of Infectious Diseases Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsuChina department of Pathology and Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina department of Infectious Diseases Rui Jin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Background and Aims:Disease progression of chronic hepatitis B virus(HBV)infection is driven by the interactions between viral replication and the host immune response against the *** study aimed to clarify the relationship between HBV replication and hepatic inflammation during disease ***:Two cross-sectional,one validation cohort,and meta-analyses were used to explore the relationship between HBV replication and liver *** analysis,multiple linear regression,and logistic regression were used to explore the relationship between ***:In the cross-sectional cohorts A and B including 1,350 chronic hepatitis B patients,Spearman analysis revealed a negative relationship between HBV replication(such as HBV DNA)and liver inflammation(such as ALT)in HBeAg-positive patients with higher HBV DNA>2×10^(6) IU/mL(rho=0.278 and 0.260)and HBeAg-negative patients(rho=0.450 and 0.363).After adjustment for sex,age,and anti-HBe,results from logistic regression and multiple linear regression showed the opposite relationship still existed in HBeAg-positive patients with different DNA levels;the opposite relationship in HBeAg-positive patients with different DNA levels was validated in a third cohort;the opposite relationship in patients with different HBeAg status was partially confirmed by meta-analysis(overall R:-0.004 vs 0.481).Conclusions:These results suggested a negative relationship between viral replication and liver inflammation in HBeAgpositive patients with high HBV DNA,which changed to a positive relationship for those HBeAg-positive patients with DNA less than 2×10^(6) IU/mL and HBeAg-negative patients.

关键词： Chronic hepatitis B HBeAg HBV DNA ALT.

New-onset primary Sjögren's syndrome following exposure to severe acute respiratory syndrome coronavirus 2: A retrospective cohort study

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Rheumatology & Autoimmunity 2024年第1期4卷 37-46页

作者： Shu liu Jing zhang Mian liu Qun Chen Shiying wang Dandan wang Lingyun Sun department of Rheumatology and Immunology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsuChina department of Rheumatology and Immunology Nanjing Drum Tower HospitalClinical College of Nanjing University of Chinese MedicineNanjingJiangsuChina

Background:Understanding the clinical implications of autoimmune manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to reduce its consequences. This study was aimed at determining the activities of new-onset primary Sjögren syndrome (pSS) since the emergence of ***:This retrospective cohort study included data from 471 participants with dry mouths and eyes who had been attending nanjing Drum Tower hospital since December 2019. By April 2023, patients diagnosed with pSS were sequentially assigned to vaccinated group ( n = 24) or vaccinated and infected group based on exposure ( n = 20). Patients diagnosed with pSS within 3 months of vaccination against SARS-CoV-2 were assigned to a vaccinated group, and those who had been vaccinated and then developed pSS within 3 months of follow up after direct exposure to SARS-CoV-2 were assigned to a vaccinated and infected group. The controls comprised age- and sex-matched patients who had not been exposed to SARS-CoV-2 before December 2019 ( n = 21). We then compared data among the three groups. Results:The vaccinated and infected patients had more fever, malaise, splenomegaly, and weight loss before diagnosis and a higher European Alliance of Associations for Rheumatology Sjögren's syndrome disease activity index at the time of onset than the other two groups. Vaccinated patients had a higher frequency of anti-nuclear antibody (ANA) titers > 1:320 ( n = 12;50%) and anti-phospholipid antibodies (aPL) ( n = 7;29%) than the controls. The frequency of anti-Ro/SSA antibodies (13, 65%), ANA titers > 1:320 ( n = 16;80%), and aPLs ( n = 7;29%) ( n = 5;25%) were all significantly higher in vaccinated patients with infection than those in the controls. Higher doses of glucocorticoids, cyclosporin A, and tacrolimus were administered to the vaccinated and infected than the vaccinated and control groups ( p < 0.05, for all). Conclusions:Patients with new-onset pSS and a h

关键词： ESSDAI primary Sjögren's syndrome SARS-CoV-2 vaccination

Surface demineralized freeze-dried bone allograft followed by reimplantation in a failed mandibular dental implant

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Regenerative Biomaterials 2024年第1期3卷 82-93页

作者： Jing zhang Jie wang Jiayi You Xuan Qin Huimin Chen Xiantong Hu Yantao Zhao Yang Xia Jiangsu Key Laboratory of Oral Diseases Nanjing Medical UniversityNanjingJiangsu 210029PR China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical UniversityNanjingJiangsu 210029PR China department of Restorative Dental Sciences Faculty of DentistryThe University of Hong KongHong Kong SARPR China Senior department of Orthopedics The Fourth Medical Center of PLA General HospitalBeijing100048PR China Beijing Engineering Research Center of Orthopedics Implants Beijing 100048PR China State Key Laboratory of Military Stomatology Xi'an 710032PR China

The removal of a failed implant with high torque causes significant damage to the surrounding tissue,compromising bone regeneration and subsequent osseointegration in the defect ***,we report a case of carrier screw fracture followed by immediate implant removal,bone grafting and delayed reimplantation.A dental implant with a fractured central carrier screw was removed using the bur-forceps *** resulting three-wall bone defect was filled with granular surface demineralized freeze-dried bone allograft(SD-FDBA).Cone-beam computerized tomography was performed at 1week,6months and 15months postoperatively and standardized for quantitative *** alveolar bone width and height at 15months post-surgery were about 91%of the original values,with a slightly lower bone density,calculated using the gray value *** graft site was reopened and was found to be completely healed with dense and vascularized bone along with some residual bone *** followed by restoration was performed 8months *** quality of regenerated bone following SD-FDBA grafting was adequate for osseointegration and longterm implant *** excellent osteogenic properties of SD-FDBA are attributed to its human origin,cortical bone-like structure,partly demineralized surfaces and bone morphogenetic protein-2-containing *** investigation with more cases and longer follow-up was required to confirm the final clinical effect.

关键词： dental implant implant failure allogeneic bone bone regeneration reimplantation

Chinese expert consensus on the diagnosis and treatment of balanoposthitis

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Chinese medical Journal 2024年第13期137卷 1519-1521页

作者： Li zhang Amer A.A.Abdulrahman Hao Guo Jia’an zhang Xinghua Gao weihua Pan Gang wang Jinhua Xu Yuling Shi liuqing Chen Hongxiang Chen Songmei Geng Yuping Ran Hongwei wang Xiaoyong Man Jianmin Chang Furen zhang Litao zhang Guangwen Yin Jianzhong zhang wei Lai Zhibin Niu Hongkun Jiang Haibo liu Yaolong Chen Jianjian wang department of Dermatology The First Hospital of China Medical UniversityShenyangLiaoning 110001China Key Laboratory of Immunodermatology Ministry of Education and NHCNational Joint Engineering Research Center for Theranostics of Immunological Skin DiseasesShenyangLiaoning 110001China department of Dermatology Chinese Academy of Medical Science and Peking Union Medical CollegeNanjingJiangsu 210042China department of Dermatology Second Affiliated Hospital of Naval Medical UniversityShanghai 200003China department of Dermatology Xijing HospitalFourth Military Medical UniversityXi’anShaanxi 710032China department of Dermatology Huashan HospitalFudan UniversityShanghai 200040China department of Dermatology Shanghai Skin Disease HospitalTongji University School of MedicineShanghai 200443China department of Dermatology Wuhan No.1 HospitalWuhanHubei 430022China department of Dermatology Huazhong University of Science and Technology Union Shenzhen HospitalShenzhenGuangdong 518052China department of Dermatology Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710004China department of Dermatovenereology West China HospitalSichuan UniversityChengduSichuan 610041China department of Dermatology Huadong HospitalFudan UniversityShanghai 200040China department of Dermatology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China department of Dermatology Beijing HospitalBeijing 100730China Shandong Provincial hospital for Skin Diseases&Shandong Provincial Institute of Dermatology and Venereology Shandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250061China department of Dermatology Tianjin Academy of Traditional Chinese Medicine Affiliated HospitalTianjin 300120China department of Dermatology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China department of Dermatology Peking University People’s HospitalBeijing 100044 China department of Dermatology Third Affi

Balanoposthitis(BP),a common male genitalia inflammation,is managed by clinicians from different specialties,including urology,pediatrics,dermatology,and *** to this diverse array of clinicians involved,there exists a lack of consistent,evidence-based recommendations for *** development of the consensus engaged 19 representative hospitals and it adhered to rigorous protocols,encompassing international registration(IPGRP-2021CN003)and the application of evidence grading criteria and recommendation standards[Appendix S1,Supplementary File,http://***/CM9/C42].Over the period from December 2020 to October 2022,consensus on 12 clinical issues was reached through comprehensive evidence searches and two iterations of Delphi surveys[Supplementary File,http://***/CM9/C42].

关键词： Delphi diagnosis rigorous

Concurrent chemoradiotherapyof different radiation doses and different irradiation fields for locally advanced thoracic esophageal squamous cell carcinoma:A randomized,multicenter,phase Ⅲ clinical trial

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Cancer Communications 2024年第10期44卷 1173-1188页

作者： Jian zhang Minghao Li Kaixian zhang Anping Zheng Guang Li wei Huang Shaoshui Chen Xiangming Chen Xiaomin Li Yanxing Sheng Xinchen Sun Liping liu Xiaowei liu Jie Li Jun wang Hong Ge Shucheng Ye Qingsong Pang Xianwen zhang Shengbin Dai Richard Yu Wendong Gu Mingming Dai Gaowa Siqin Yunwei Han Xiaolin Ge Xin Yuan Yongjing Yang Haiwen Zhu Juan Pu Lihua Dong Xiangdong Sun Jundong Zhou weidong Mao Fei Gao Haiqun Lin Heyi Gong Tao Zhou Zhenjiang Li Hongsheng Li Zhongtang wang Baosheng Li department of Oncology Central Hospital Affiliated to Shandong First Medical UniversityJinanShandongP.R.China department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongP.R.China department of Oncology Tengzhou Central People’s HospitalTengzhouShandongP.R.China department of Radiation Oncology Anyang Tumor HospitalAnyangHenanP.R.China department of Radiation Oncology the First Hospital of China Medical UniversityShenyangLiaoningP.R.China department of Oncology Binzhou Medical University HospitalBinzhouShandongP.R.China department of Oncology Taian CentralHospitalTaianShandongP.R.China department of Radiation Oncology Shanxi Province Cancer HospitalTaiyuanShanxiP.R.China department of Oncology Liaocheng People’s HospitalLiaochengShandongP.R.China department of Radiation Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China department of Oncology Jining First People′s HospitalJiningShandongP.R.China department of Oncology the Affiliated Hospital of Jining Medical UniversityJiningShandongP.R.China department of Radiation Oncology the Fourth Hospital of Hebei Medical UniversityHebei Clinical Research Center for Radiation OncologyShijiazhuangHebeiP.R.China department of Radiation Oncology the Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China department of Radiation Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory ofCancer Prevention and TherapyTianjin’s ClinicalResearch Center for CancerTianjinP.R.China department of Oncology Subei People’s Hospital of Jiangsu ProvinceYangzhouJiangsuP.R.China department of Oncology Taizhou People’s Hospital of Jiangsu ProvinceTaizhouZhejiangP.R.China department of Radiation Oncology the Affiliated Hospital of Inner Mongolia Medical UniversityHohhotInner MongoliaP.R.China department of Radiation O

Background:Concurrent chemoradiotherapy(CCRT)is the standard treatment for locally advanced esophageal squamous cell carcinoma(ESCC).However,the optimal radiotherapy regimen,particularly in terms of total dose and planned range of irradiation field,remains *** phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target ***:This trial compared two aspects of radiation treatment,total dose and field,using a two-by-two factorial *** high-dose(HD)group received 59.4 Gy radiation,and the standard-dose(SD)group received 50.4 *** involved field irradiation(IFI)group and elective nodal irradiation(ENI)group adopted different irradiation *** participants were assigned to one of the four groups(HD+ENI,HD+IFI,SD+ENI and SD+IFI).The primary endpoint was overall survival(OS),and the secondary endpoints included progressionfree survival(PFS).The synergy indexwas used to measure the interaction effect between dose and ***:The interaction analysis did not reveal significant synergistic effects between the dose and irradiation *** comparison to the target field,patients in IFI or ENI showed similar OS(hazard ratio[HR]=0.99,95%CI:0.80-1.23,p=0.930)and PFS(HR=1.02,95%CI:0.82–1.25).TheHDtreatment did not show significantly prolonged OS compared with SD(HR=0.90,95%CI:0.72–1.11,p=0.318),but it suggested improved PFS(25.2 months to 18.0 months).Among the four groups,the HD+IFI group presented the best survival,while the SD+IFI group had the worst *** significant difference in the occurrence of severe adverse events was found in dose or field ***:IFI demonstrated similar treatment efficacy to ENI in CCRT of *** HD demonstrated improved PFS,but did not significantly improve *** dose escalation based on IFI(HD+IFI)showed better therapeutic efficacy than the current recommendation(SD+ENI)and is worth further validation.

关键词： clinical trial concurrent chemoradiotherapy elective nodal radiation esophageal squamous cell carcinoma high dose radiation involved field radiation overall survival standard dose radiation