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Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1647-1659页

作者： Ju-Hang Chu Lu-Yao Huang Ya-Ru Wang Jun Li shi-Long Han Hao Xi Wen-Xue Gao Ying-Yu Cui Ming-Ping Qian Department of General surgery Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghai 200072China Department of Interventional and Vascular surgery Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghai 200072China Department of Pathology Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghai 200072China Clinical Research Management Office Shanghai Tenth People’s HospitalShanghai 200072China Department of Cell Biology Institute of Medical GeneticsState Key Laboratory of CardiologyTongji University School of MedicineShanghai 200331China

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical *** demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and sintilimab is useful for patients with advanced *** sUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal *** computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/***,he was judged to have advanced *** treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of *** the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be *** pathological diagnosis indicated a complete *** patient recovered well after the operation,and no tumor recurrence was *** Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant *** drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

关键词： Hepatocellular therapy Conversion hepatectomy Interventional therapy Epclusa Lenvatinib sintilimab Case report

Physical exercise reverses immuno-cold tumor microenvironment via inhibiting sQLE in non-small cell lung cancer

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Military medical Research 2024年第4期11卷 616-619页

作者： Zhi-Wen Luo Ya-Ying sun Wei Xia Jun-Ying Xu Dong-Jing Xie Chun-Meng Jiao Ji-Ze Dong Hui Chen Ren-Wen Wan shi-Yi Chen Jie Mei Wen-Jun Mao Department of sports Medicine Huashan Hospital Affiliated to Fudan UniversityShanghai 200040China Department of sports Medicine Shanghai General HospitalShanghai 200080China Department of Critical Care Medicine the Affiliated Wuxi People’s Hospital of Nanjing Medical UniversityWuxi 214023JiangsuChina Department of Oncology the Affiliated Wuxi People’s Hospital of Nanjing Medical UniversityWuxi 214023JiangsuChina Guangdong Pharmaceutical university Guangzhou 510006China Institute of Acupuncture Research Institutes of Integrative MedicineFudan UniversityShanghai 200433China Department of Cardiothoracic surgery the Affiliated Wuxi People’s Hospital of Nanjing Medical UniversityWuxi 214023JiangsuChina

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are *** regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

关键词： Physical exercise Non-small cell lung cancer(NsCLC) squalene epoxidase(sQLE) Tumor immune microenvironment(TIME)

First-line camrelizumab(a PD-1 inhibitor)plus apatinib(an VEGFR-2 inhibitor)and chemotherapy for advanced gastric cancer(sPACE):a phase 1 study

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signal Transduction and Targeted Therapy 2024年第4期9卷 1760-1767页

作者： Xiaofeng Chen Hao Xu Xiaobing Chen Tongpeng Xu Yitong Tian Deqiang Wang Fen Guo Kangxin Wang Guangfu Jin Xiao Li Rong Wang Fengyuan Li Yongbin Ding Jie Tang Yueyu Fang Jing Zhao Liang Liu Ling Ma Lijuan Meng Zhiguo Hou Rongrong Zheng Yang Liu Ni Guan Bei Zhang shuang Tong shiqing Chen Xing Li Yongqian shu Department of Oncology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Gusu school Nanjing medical UniversitySuzhouChina Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingChina Department of General surgery The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of Oncology Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouChina Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer&Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer ZhengzhouChina Department of Oncology Digestive Disease Institute&Cancer Institute of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology Suzhou Hospital of Nanjing Medical UniversitySuzhouChina Department of Oncology Nanjing PuKou People’s HospitalNanjingChina Department of Epidemiology School of Public HealthNanjing Medical UniversityNanjingChina Department of Pathology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of general surgery Jurong Branch hospital of Jiangsu Province People HospitalJurongChina Department of medical Oncology Liyang People’s HospitalLiyangChina Department of radiology Nanjing PuKou People’s HospitalNanjingChina Jiangsu Hengrui Pharmaceuticals ShanghaiChina Department of medical Affairs 3D Medicines Inc.ShanghaiChina shanghai OrigiMed Co. Ltd.ShanghaiChina

Patients with advanced gastric cancer typically face a grim *** phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapyfor advanced gastric or gastroesophageal junction *** primary endpoints included maximum tolerated dose(MTD)in phase 1a and objective response rate(ORR)across phase 1a and *** 1a tested three dose regimens of camrelizumab,apatinib,oxaliplatin,and *** regimen 1:camrelizumab 200 mg on day 1,apatinib 250 mg every other day,oxaliplatin 100 mg/m^(2) on day 1,and s-140 mg twice a day on days *** regimen 2:same as dose regimen 1,but oxaliplatin 130mg/*** regimen3:same as dose regimen 2,but apatinib 250 mg ***-four patients were included(9 in phase 1a,25 in phase 1b).No dose-limiting toxicities occurred so no MTD was *** 3 was set for the recommended phase 2 doses and administered in phase *** confrmed ORR was 76.5%(95%CI 58.8-89.3).The median progression-free survival was 8.4 months(95%CI 5.9-not evaluable[NE]),and the median overall survival(Os)was not mature(11.6-NE).Ten patients underwent surgery after treatment and the multidisciplinary team *** 24 patients without surgery,the median Os was 19.6 months(7.8-NE).Eighteen patients(52.9%)developed grade≥3 treatment-emergent adverse *** plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer(ChiCTR2000034109).

关键词： regimen cancer doses

Modeling human gastric cancers in immunocompetent mice

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Cancer Biology & Medicine 2024年第7期21卷 553-570页

作者： Weihong Zhang shilong Wang Hui Zhang Yan Meng shi Jiao Liwei An Zhaocai Zhou Department of stomatology Department of Medical UltrasoundShanghai Tenth People's HospitalTongji University Cancer CenterTongji University School of MedicineShanghai 200072China state Key Laboratory of Genetic Engineering School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China Collaborative Innovation Center for Cancer Personalized Medicine School of Public HealthNanjing Medical UniversityNanjing 211166China

Gastric cancer(GC)is a major cause of cancer-related mortality *** is determined by multiple(epi)genetic and environmental factors;can occur at distinct anatomic positions of the stomach;and displays high heterogeneity,with different cellular origins and diverse histological and molecular *** heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient *** the past decade,great progress has been made in the study of GC,particularly in molecular subtyping,investigation of the immune microenvironment,and defining the evolutionary path and *** mouse models,particularly immunocompetent models that mimic the cellular and molecular features of human GC,in combination with organoid culture and clinical studies,have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion,and the development of novel therapeutic ***,we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models,emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.

关键词： Gastric cancer heterogeneity mouse model GEMM immunocompetent

Development and validation of a novel criterion of histologic healing in ulcerative colitis defined by inflammatory cell enumeration in lamina propria mucosa:A multicenter retrospective cohort in China

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Chinese medical Journal 2024年第11期137卷 1316-1323页

作者： Han Gao Kangsheng Peng Yadi shi shenshen Zhu Ruicong sun Chunjin Xu Ping Liu Zhi Pang Lanxiang Zhu Weichang Chen Baisui Feng Huili Wu Guangxi Zhou Mingsong Li Junxiang Li Baijing Ding Zhanju Liu Center for IBD Research and Department of Gastroenterology Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200085China Clinical Medicine Sanquan College of Xinxiang Medical UniversityXinxiangHenan 453003China Department of Gastroenterology The First People’s Hospital of Shangqiu City Affiliated to Xinxiang Medical UniversityShangqiuHenan 476100China Department of Gastroenterology Wuhu First People’s HospitalWuhuAnhui 241000China Department of Gastroenterology Suzhou Municipal Hospital Affiliated to Nanjing Medical UniversitySuzhouJiangsu 215008China Department of Gastroenterology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 251006China Department of Gastroenterology The Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450014China Department of Gastroenterology Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhouHenan 450000China Department of Gastroenterology The Affiliated Hospital of Jining Medical CollegeJiningShandong 272004China Department of Gastroenterology The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510140China Department of Gastroenterology Dongfang Hospital of Beijing University of Chinese MedicineBeijing 100078China

Background:Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis(UC).Here,we developed a novel diagnostic criterion for assessing histological healing in UC ***:We conducted a retrospective cohort study in UC patients,whose treatment was iteratively optimized to achieve mucosal healing at shanghai tenth people’s hospital of Tongji university from January 2017 to May *** identified an inflammatory cell enumeration index(ICEI)for assessing histological healing based on the proportions of eosinophils,CD177^(+)neutrophils,and CD40L^(+)T cells in the colonic lamina propria under high power field(HPF),and the outcomes(risks of symptomatic relapses)of achieving histological remission *** histological inflammation using Kaplan-Meier *** reliability and inter-reader reliability were evaluated by each *** relationships to the changes in the Nancy index and the Geboes score were also assessed for *** ICEI was further validated in a new cohort of UC patients from other nine university ***:We developed an ICEI for clinical diagnosis of histological healing,i.e.,Y=1.701X_(1)+0.758X_(2)+1.347X_(3)-7.745(X_(1),X_(2),and X_(3)represent the proportions of CD177^(+)neutrophils,eosinophils,and CD40L^(+)T cells,respectively,in the colonic lamina propria under HPF).The receiver operating characteristics curve(ROC)analysis revealed that Ys the cutoff value for the diagnosis of histological healing and that an area under the curve(AUC)was 0.942(95%confidence interval[CI]:0.905-0.979)with a sensitivity of 92.5%and a specificity of 83.6%(Pss correlation coefficient(ICC)for the intrareader reliability was 0.855(95%CI:0.781-0.909),and ICEI had good inter-reader reliability of 0.832(95%CI:0.748-0.894).During an 18-month follow-up,patients with histological healing had a substantially better outcome com

关键词： Ulcerative colitis Histological healing Inflammatory cell enumeration index Prognosis

self‑Healing Dynamic Hydrogel Microparticles with structural Color for Wound Management

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Nano-Micro Letters 2024年第11期16卷 177-190页

作者： Li Wang Xiaoya Ding Lu Fan Anne M.Filppula Qinyu Li Hongbo Zhang Yuanjin Zhao Luoran shang Department of General surgery Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025People’s Republic of China Department of Rheumatology and Immunology Nanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096People’s Republic of China Pharmaceutical sciences Laboratory Åbo Akademi University20520 TurkuFinland Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325001People’s Republic of China shanghai Xuhui Central hospital Zhongshan‑Xuhui Hospitaland the Shanghai Key Laboratory of Medical Epigeneticsthe International Co‑laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)Institutes of Biomedical SciencesFudan UniversityShanghai 200032People’s Republic of China

Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing *** is vital to develop multifunctional hydrogel dressings,with well-designed morphology and structure to enhance flexibility and effectiveness in wound *** achieve these,we propose a self-healing hydrogel dressing based on structural color microspheres for wound *** microsphere comprised a photothermal-responsive inverse opal framework,which was constructed by hyaluronic acid methacryloyl,silk fibroin methacryloyl and black phosphorus quantum dots(BPQDs),and was further re-filled with a dynamic *** dynamic hydrogel filler was formed by Knoevenagel condensation reaction between cyanoacetate and benzaldehyde-functionalized dextran(DEX-CA and DEX-BA).Notably,the composite microspheres can be applied arbitrarily,and they can adhere together upon near-infrared irradiation by leveraging the BPQDs-mediated photothermal effect and the thermoreversible stiffness change of dynamic ***,eumenitin and vascular endothelial growth factor were co-loaded in the microspheres and their release behavior can be regulated by the same ***,effective monitoring of the drug release process can be achieved through visual color *** microsphere system has demonstrated desired capabilities of controllable drug release and efficient wound *** characteristics suggest broad prospects for the proposed composite microspheres in clinical applications.

关键词： Black phosphorus structural color Dynamic hydrogel Inverse opal Wound management

Genetic landscape and clinical significance of cuproptosis-related genes in liver hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 516-519页

作者： Dingtao Hu Yichuan Wang Xu shen Tiantian Mao Xijun Liang Tengjiao Wang Weifeng shen Yugang Zhuang Jin Ding Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghai 200433China Department of Emergency Shanghai Tenth People's HospitalTongji UniversitySchool of MedicineShanghai 200072China Bioinformatics Analysis Laboratory Center for Translational MedicineNaval Medical UniversityShanghai 200433China The Department of Hepatic surgery Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China

Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-s cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAs,FDX1,CDKN2A,GLs,and MTF1.1 since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.s1A;Fig.1A),suggesting the distinct role of CRGs in *** then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical *** detailed methods were described in the supplementary material.

关键词： clinical metabolism hepatocellular

GRK2-YAP signaling is implicated in pulmonary arterial hypertension development

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Chinese medical Journal 2024年第7期137卷 846-858页

作者： Peng Ye Yunfei Deng Yue Gu Pengfei Liu Jie Luo Jiangqin Pu Jingyu Chen Yu Huang Nanping Wang Yong Ji shaoliang Chen Division of Cardiovascular Molecular Laboratory Third Clinical CollegeNanjing Medical UniversityNanjingJiangsu 210006China Division of Cardiovascular Laboratory Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China Division of Cardiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200080China Division of Pulmonary surgery Wuxi People’s HospitalNanjing Medical UniversityWuxiJiangsu 300247China Institute of Vascular Medicine The Chinese University of Hong KongHongkong 999077China Health science Center East China Normal UniversityShanghai 200241China school of Pharmacy Nanjing Medical UniversityNanjingJiangsu 210004China Division of Cardiology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China

Background:Pulmonary arterial hypertension(PAH)is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells(PAsMCs),endothelial dysfunction,and extracellular matrix remodeling.G protein-coupled receptor kinase 2(GRK2)plays an important role in the maintenance of vascular tone and blood ***,the role of GRK2 in the pathogenesis of PAH is ***:GRK2 levels were detected in lung tissues from healthy people and PAH patients.C57BL/6 mice,vascular smooth muscle cell-specific Grk2-knockout mice(Grk2^(∆sM22)),and littermate controls(Grk2^(flox/flox))were grouped into control and hypoxia mice(n=8).Pulmonary hypertension(PH)was induced by exposure to chronic hypoxia(10%)combined with injection of the sU5416(cHx/sU).The expression levels of GRK2 and Yes-associated protein(YAP)in pulmonary arteries and PAsMCs were detected by Western blotting and immunofluorescence *** mRNA expression levels of Grk2 and Yes-associated protein(YAP)in PAsMCs were quantified with real-time polymerase chain reaction(RT-PCR).Wound-healing assay,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)assay,and 5-Ethynyl-2′-deoxyuridine(EdU)staining were performed to evaluate the proliferation and migration of ***,the interaction among proteins was detected by immunoprecipitation ***:The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH ***,cHx/sU-induced PH was attenuated in Grk2^(∆sM22) mice compared with littermate *** amelioration of PH in Grk2^(∆sM22) mice was accompanied by reduced pulmonary vascular *** vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PAsMCs proliferation and migration,whereas this effect was severely intensified by overexpression of *** also identified that GRK2 promoted YAP expression and nuclear translocation in PAsMCs,resulting in excessive PA

关键词： Pulmonary arterial hypertension GRK2 YAP Pulmonary artery smooth muscle cell Hypoxia

Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation

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Protein & Cell 2024年第7期15卷 512-529页

作者： Kai-Hui Zhang Fei-Fei Zhang Zhi-Ling Zhang Ke-Fei Fang Wen-Xing sun Na Kong Min Wu Hai-Ou Liu Yan Liu Zhi Li Qing-Qing Cai Yang Wang Quan-Wei Wei Peng-Cheng Lin Yan Lin Wei Xu Cong-Jian Xu Yi-Yuan Yuan shi-Min Zhao The Obstetrics&Gynecology hospital of Fudan university State Key Laboratory of Genetic EngineeringFudan UniversityShanghai 200090China shanghai Key Laboratory of Metabolic Remodeling and Children’s Hospital of Fudan UniversityShanghai 200032China school of Life sciences and Institutes of Biomedical sciences Fudan UniversityShanghai 200438China Department of Nutrition and Food Hygiene School of Public HealthNantong UniversityNantong 226019China Reproductive Medicine Center The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China shanghai Fifth people’s hospital of Fudan university Fudan UniversityShanghai 200240China Department of Animal science and Technology Nanjing Agricultural UniversityNanjing 210014China Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province College of PharmacyQinghai University for NationalitiesXining 810007China Pediatric Research Institute Children’s Hospital Affiliated to Shandong University(Jinan Children’s Hospital)Jinan 250022China

Polycystic ovary syndrome(PCOs)is the leading cause of anovulatory *** understanding of the ovulation drivers hinders PCOs ***,we report that follicle stimulating hormone(FsH)controls follicular fluid(FF)glutamine levels to determine *** ovulation starts from FF-exposing granulosa cell(GC)*** glutamine,which decreases in pre-ovulation porcine FF,elevates in PCOs patients ***-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal,metabolic,and morphologic PCOs ***,follicle-development-driving FsH promotes GC glutamine synthesis to elevate FF glutamine,which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating AsK1-JNK apoptotic *** and glutamine inhibit the rapture of cultured murine *** removal or AsK1-JNK pathway activation with metformin or AT-101 reversed PCOs traits in PCOs models that are induced with either glutamine or *** suggest that glutamine,FsH,and AsK1-JNK pathway are targetable to alleviate PCOs.

关键词： ovulation glutamine granulosa cells PCOs FsH