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Hepatic vein reconstruction during hepatectomy:A feasible and underused technique

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 421-427页

作者： Manish Ahuja Kunal Joshi Chris Coldham Paulo Muiesan Bobby Dasari Manuel Abradelo Ravi Marudanayagam Darius Mirza John Isaac David Bartlett Nikolaos A Chatzizacharias Robert P Sutcliffe Keith J Roberts Department of HPB and Liver Transplant surgery University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Immunology and Immunotherapy University of BirminghamBirminghamUK

Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].tumors invading to the proximity of the hepatic venous outflow pose a peculiar challenge to achieve R0 resections,because this location may render a tumor *** median survival of patients with liver tumor without surgery is less than 12 months[2].Even with surgery,post-hepatectomy liver failure and subsequently increased mortality are the main problems associated with complex resection[3].Moreover,when the vein is affected,vein resection and subsequent reconstruction are *** resection is a standard practice in liver resection and transplantation[4],for example,hepatic vein reconstruction during a living-donor liver transplant,porto-mesenteric axis reconstruction during resection of advanced pancreatic cancer and caval reconstruction during resection of retroperitoneal ***,novel techniques like total hepatic vascular exclusion(HVE)[5],veno-venous bypass[6]and ex vivo hepatic resection[7,8]have facilitated curative resections of tumors close to one or more major hepatic veins.

关键词： hepatectomy surgery mortality

Whole breast ultrafractionation radiotherapy after breast-conserving surgery in early breast cancer: A single-center, prospective, observational study from China

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Malignancy Spectrum 2024年第2期1卷 113-122页

作者： Rui-Zhi Zhao Cheng Huang Tian-Lan Tang Gui-Qing Shi Si-Lin Chen Yu-Ping Lin Ying Wang Liu-Qing Jiang Jin-Hua Chen Chun-Sen Xu Fang-Meng Fu Zhong-Hua Han Shun-Guo Lin Chuan Wang Yong Yang Department of Radiation Oncology Fujian Medical University Union HospitalFujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors(Fujian Medical University)Clinical Research Center for Radiology and Radiotherapy of Fujian Province(DigestiveHematological and Breast Malignancies)FuzhouFujianChina Department of Follow-Up Center Fujian Medical University Union HospitalFuzhouFujianChina Department of Breast surgery Fujian Medical University Union HospitalFuzhouFujianChina

Objective:This single-center,prospective,observational study was designed to investigate the toxicities,patient-reported outcome(PRO),and dosimetric analysis of whole breast ultrafractionation radiotherapy(RT)after breast-conserving surgery(BCS)in early breast cancer(BC).Patients and methods:Patients diagnosed with BC stage I,II and treated with BCS were enrolled.A dose of 26 Gray(Gy)in five fractions was prescribed to the whole breast and tumor *** endpoints included toxicities,PRO,and dosimetric *** was measured by the European Organization for Research and Treatment of Cancer general quality of life questionnaire(EORTC QLQ-C30)and the BC-specific questionnaire(EORTC QLQ-BR23)***:Between January 2022 and June 2023,62 female patients were *** median age was 45 *** patients(83.9%)were diagnosed with pathological stage I *** median planning target volume(PTV)was 456.4 *** minimum,maximum,and mean doses,and D95(dose of PTV irradiated volume more than 95%)to PTV were 20.2,28.8,27.2,and 26.3 Gy,*** median mean lung dose and percentage lung volume receiving 8 Gy(V8)were 3.6 Gy and 13.4%,*** median mean heart dose,V1.5(percentage of organ volume irradiated with 1.5 Gy or higher),and V7(percentage of organ volume irradiated with 7 Gy or higher)were 0.6 Gy,6.8%,and 0.4%,*** effects before RT showed no obvious differences compared to that post *** toxicities of grade 3 or higher *** patients had asymptomatic radiation pneumonia(grade 1),and 12 patients had radiation dermatitis(grade 1).No factor was significantly related to radiation dermatitis or radiation *** the EORTC QLQ-C30 and QLQ-BR23 questionnaires,all function and symptom scores before RT had no significant differences compared with that after RT,1−2 months after RT,and 3−4 months after *** RT did not worsen *** 1-year crude local control was 100%.Conclusion:Whole br

关键词： ultrafractionation radiotherapy breast cancer breast-conserving surgery toxicities patient-reported outcome

Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma

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Cancer Communications 2024年第2期44卷 226-250页

作者： Weiren Liu Huqiang Wang Qianfu Zhao Chenyang Tao Weifeng Qu Yushan Hou Run Huang Zimei Sun Guiqi Zhu Xifei Jiang Yuan Fang Jun Gao Xiaoling Wu Zhixiang Yang Rongyu Ping Jiafeng Chen Rui Yang Tianhao Chu Jian Zhou Jia Fan Zheng Tang Dong Yang Yinghong Shi Department of Liver surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationShanghaiP.R.China Research unit of Liver cancer Recurrence and Metastasis Chinese Academy of Medical SciencesBeijingP.R.China State Key Laboratory of Medical Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingP.R.China

Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic *** metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely ***,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat ***:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome *** on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was *** and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic *** proliferation analysis,5-ethynyl-2’-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA ***:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were *** metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic *** S2 subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)*** the S2 subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)***:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing

关键词： diacylglycerol kinaseα intrahepatic cholangiocarcinoma MAPK signaling metabolic classifi-cation multiomics analysis phosphatidic acid metabolism

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

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

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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

Diagnosis and treatment of biliary mucinous cystic neoplasms: A single-center experience

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 495-501页

作者： Jun-Jun Jia Ya-Fen Cheng Mei-Bao Feng Li Liu Ming-Qi Shuai Xiao-Dong Shen Xiao-Feng Tang Shu-Sen Zheng Division of Hepatobiliary and Pancreatic surgery Department of Surgerythe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of International Healthcare Center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Pathology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Library the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: Biliary mucinous cystic neoplasms(BMCNs) are rare hepatobiliary cystic tumors, which can be divided into noninvasive and invasive types. This study aimed to investigate the diagnosis, treatment, and prognosis of BMCNs in a large single center. Methods: We analyzed 49 patients with BMCNs confirmed by postoperative pathology at the First Afflliated Hospital, Zhejiang University School of Medicine between January 2007 and December 2021. Results: Among the 49 patients, 37 were female(75.5%), and the average age was 57.04 years. Common symptoms included abdominal discomfort, jaundice and fever, while 22 patients(44.9%) had no symptoms. Serum carbohydrate antigen(CA) 19-9 and CA125 concentrations were elevated in 34.8% and 19.6% of patients, respectively. Forty-eight patients had tumors in the intrahepatic bile ducts and only one had a tumor in the extrahepatic bile duct. Forty-eight patients with noninvasive intrahepatic BMCNs were further analyzed in terms of pathological features: 34(70.8%) had low-grade intraepithelial neoplasms(LGINs), and 14(29.2%) had high-grade intraepithelial neoplasms(HGINs). The potential immunohistochemical markers of BMCNs were cytokeratin(CK) 19, CK7, estrogen receptor and progesterone receptor. Follow-up data for 37 patients with intrahepatic BMCNs were obtained. The median overall survival(OS) of BMCNs was not reached. The longest survival time was 137 *** 5-and 10-year OS rates were 100% and 85.4%, respectively. The 5-and 10-year recurrence-free survival(RFS) rates were 93.9% and 80.2%, respectively. Conclusions: BMCNs are rare cystic neoplasms that commonly occur in middle-aged females. BMCNs can only be diagnosed and classified by postoperative pathology, as there are no specific clinical presentations, serological indicators or imaging modalities for preoperative diagnosis. Complete surgical resection is necessary for BMCNs, and the postoperative prognosis is favorable.

关键词： Biliary mucinous cystic neoplasms Low-grade intraepithelial neoplasms High-grade intraepithelial neoplasms Overall survival Recurrence-free survival

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

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Neural Regeneration Research 2025年第7期20卷 1883-1899页

作者： Mingyu Zhang Chunyu Xiang Renrui Niu Xiaodong He Wenqi Luo Wanguo Liu Rui Gu Department of Orthopedic surgery China-Japan Union Hospital of Jilin UniversityChangchunJilin ProvinceChina

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely ***,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic *** are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and ***,they can potentially treat traumatic and nontraumatic central nervous system *** this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics ***,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain *** studies related to liposomes are still in the laboratory stage and have not yet entered clinical ***,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and ***,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

关键词： Alzheimer's disease amyotrophic lateral sclerosis brain tumors central nervous system Huntington's disease liposome drug delivery neurological disorders Parkinson's disease spinal cord injury traumatic brain injury

Effects of dietary intervention on human diseases:molecular mechanisms and therapeutic potential

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1389-1422页

作者： Yu-Ling Xiao Yue Gong Ying-Jia Qi Zhi-Ming Shao Yi-Zhou Jiang Key Laboratory of Breast Cancer in Shanghai Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudanUniversityShanghai200032China

Diet,serving as a vital source of nutrients,exerts a profound influence on human health and disease ***,dietary interventions have emerged as promising adjunctive treatment strategies not only for cancer but also for neurodegenerative diseases,autoimmune diseases,cardiovascular diseases,and metabolic *** interventions have demonstrated substantial potential in modulating metabolism,disease trajectory,and therapeutic *** reprogramming is a hallmark of malignant progression,and a deeper understanding of this phenomenon in tumors and its effects on immune regulation is a significant challenge that impedes cancer *** intake,as a key environmental factor,can influence tumor *** evidence indicates that dietary interventions might affect the nutrient availability in tumors,thereby increasing the efficacy of cancer ***,the intricate interplay between dietary interventions and the pathogenesis of cancer and other diseases is *** encouraging results,the mechanisms underlying diet-based therapeutic strategies remain largely unexplored,often resulting in underutilization in disease *** this review,we aim to illuminate the potential effects of various dietary interventions,including calorie restriction,fasting-mimicking diet,ketogenic diet,protein restriction diet,high-salt diet,high-fat diet,and high-fiber diet,on cancer and the aforementioned *** explore the multifaceted impacts of these dietary interventions,encompassing their immunomodulatory effects,other biological impacts,and underlying molecular *** review offers valuable insights into the potential application of these dietary interventions as adjunctive therapies in disease management.

关键词： diseases metabolism potential

Uniportal video-assisted thoracoscopic fissureless right upper lobe anterior segmentectomy for inflammatory myofibroblastic tumor:A case report

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World Journal of Clinical Cases 2024年第2期12卷 425-430页

作者： Seha Ahn Youngkyu Moon Department of Thoracic and Cardiovascular surgery Eunpyeong St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 03312South Korea

BACKGROUND Inflammatory myofibroblastic tumors(IMTs)are exceptionally rare neoplasms with intermediate malignant *** is the accepted treatment option,aiming for complete resection with clear *** SUMMARY A 39-year-old woman presented with a growing solitary pulmonary nodule measuring 2.0 cm in the right upper lobe(RUL)of the *** patient underwent a RUL anterior segmentectomy using uniportal video-assisted thoracoscopy.A preliminary tissue diagnosis indicated malignancy;however,it was later revised to an *** to the absence of a minor fissure between the right upper and middle lobes,an alternative resection approach was ***,we utilized indocyanine green injection to aid in delineating the intersegmental *** an uneventful recovery,the patient was discharged on the third postoperative ***,annual chest tomography scans were scheduled to monitor for potential local *** This case underscores the challenges in diagnosing and managing IMTs,showing the importance of accurate pathologic assessments and tailored surgical strategies.

关键词： Uniportal video-assisted thoracoscopic surgery Fissureless Anterior segmentectomy Inflammatory fibroblastic tumor Case report