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The emerging tumor microbe microenvironment: From delineation to multidisciplinary approach-based interventions

Acta Pharmaceutica Sinica B 2024年第4期14卷 1560-1591页

作者： Yu Fu Jia Li Wenyun Cai Yulan Huang Xinlong Liu Zhongyi Ma Zhongjie Tang Xufei Bian Ji Zheng Jiayun Jiang Chong Li Medical Research Institute College of Pharmaceutical SciencesSouthwest UniversityChongqing 400715China Institute of Hepatobiliary surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Urology Urologic Surgery CenterXinqiao HospitalThird Military Medical University(Army Medical University)Chongqing 400037China

Intratumoral microbiota has become research hotspots,and emerges as a non-negligent new component of tumor microenvironments(TME),due to its powerful infuence on tumor initiation,metas-tasis,immunosurveillance and prognosis despite in *** accumulations of microbes,and their related components and metabolites within tumor tissues,endow TME with additional pluralistic features which are distinct from the conventional ***,it's definitely necessary to comprehen-sively delineate the sophisticated landscapes of tumor microbe microenvironment,as well as their func-tions and related underlying ***,in this review,we focused on the fields of tumor microbe microenvironment,including the heterogeneity of intratumor microbiota in different types of tu-mors,the controversial roles of intratumoral microbiota,the basic features of tumor microbe microenvi-ronment(i.e.,pathogen-associated molecular patterns(PAMPs),typical microbial metabolites,autophagy,infammation,multi-faceted immunomodulation and chemoresistance),as well as the multi-disciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes,microbiota metabolites,antibiotics,synthetic biology and rationally de-signed *** hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial,and facilitate the development of microbes-based tumor-specific treatments.

关键词： Tumor microbe microenvironment Microbiota metabolites Immunomodulation Chemoresistance Multidisciplinary approach Genetically engineered microbiota Autophagy Outer membrane vesicles

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Construction of millimeter-scale vascularized engineered myocardial tissue using a mixed gel

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Regenerative Biomaterials 2024年第3期3卷 56-67页

作者： Ming Ke Wenhui Xu Yansha Hao Feiyang Zheng Guanyuan Yang Yonghong Fan Fangfang Wang Zhiqiang Nie Chuhong Zhu Department of Anatomy Third Military Medical UniversityChongqing 400038China State Key Laboratory of Trauma Burn and Combined InjuryChongqing 400038China Department of Plastic and Aesthetic surgery Southwest HospitalThird Military Medical UniversityChongqing 400038China Engineering Research center of Tissue and Organ Regeneration and Manufacturing Ministry of EducationChongqing 400038China

Engineering myocardium has shown great clinal potential for repairing permanent myocardial ***,the lack of perfusing blood vessels and difficulties in preparing a thick-engineered myocardium result in its limited clinical *** prepared a mixed gel containing fibrin(5 mg/ml)and collagen I(0.2 mg/ml)and verified that human umbilical vein endothelial cells(HUVECs)and human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)could fom microvascular lumens and myocardial cell clusters by harnessing the low-hardness and hyperelastic characteristics of ***-CMs and HUVECs in the mixed gel formed self-organized cell clusters,which were then cultured in different media using a three-phase *** successfully constructed vascularized engineered myocardial tissue had a spherical structure and final diameter of *** tissue exhibited autonomous beats that occured at a frequency similar to a normal human heart *** internal microvascular lumen could be maintained for 6 weeks and showed good results during preliminary surface re-vascularization in vitro and vascular remodeling in *** summary,we propose a simple method for constructing vascularized engineered myocardial tissue,through phased cultivation that does not rely on high-end manufacturing equipment and cutting-edge preparation *** constructed tissue has potential value for clinical use after preliminary evaluation.

关键词： engineered myocardium vascularized hiPSC-CM HUVEC fibrin

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Emerging role of molecular diagnosis and personalized therapy for hepatocellular carcinoma

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iLIVER 2024年第1期3卷 38-44页

作者： Ming-Da Wang Yong-Kang Diao Lan-Qing Yao Zhong-Qi Fan Ke-Chun Wang Han Wu Li-Hui Gu Jia-Hao Xu Chao Li Guo-Yue Lv Tian Yang Department of Hepatobiliary surgery Eastern Hepatobiliary Surgery HospitalSecond Military Medical University(Navy Medical University)Shanghai 200438China Department of Hepatobiliary and Pancreatic surgery General Surgery CenterFirst Hospital of Jilin UniversityChangchun 130021China

Hepatocellular carcinoma(HCC)is a prevalent malignancy worldwide,ranking as the sixth most common malignancy and the third leading cause of cancer-related *** diagnosis,limited management options,and its complex etiology contribute to the poor prognosis and high mortality *** advances in understanding the molecular mechanisms of HCC and innovations in high-throughput sequencing technologies have led to the development of molecular diagnostics and personalized therapies for this challenging *** review provides a comprehensive overview of research on the molecular diagnosis and individualized treatment for *** highlight key advances and potential future directions and discuss the application of next-generation sequencing technologies to identify and characterize genetic and epigenetic alterations in HCC *** technologies may aid in the selection of targeted therapies,prediction of treatment response,and monitoring disease ***,we explore the role of liquid biopsy in HCC diagnosis,prognosis prediction,and treatment monitoring,focusing on circulating tumor cells,circulating tumor DNA,and extracellular *** also explore the evolving landscape of personalized therapy for HCC,including targeted therapies against key oncogenic signaling pathways,immune checkpoint inhibitors,tumor-agnostic therapies,and innovative cellbased *** discuss the challenges and opportunities that lie ahead in the quest to improve HCC patient outcomes through the integration of molecular diagnostics and individualized precision *** emphasize the need for multi-interdisciplinary collaboration,refinement of predictive and prognostic biomarkers,and the development of more effective combination strategies for HCC management in the new area of precision medicine.

关键词： Hepatocellular carcinoma Liquid biopsy Diagnosis Immune checkpoint inhibitors Targeted therapy

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BTF3L4 Overexpression Mediates APAP-induced Liver Injury in Mouse and Cellular Models

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Journal of Clinical and Translational Hepatology 2024年第3期12卷 245-256页

作者： Junchao Lin Aqiang Fan Zhujin Yifu Qibing Xie Liu Hong Wei Zhou State Key Laboratory of Cancer Biology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesAir Force Military Medical UniversityXi’anShaanxiChina Department of Digestive surgery Xijing HospitalAir Force Military Medical UniversityXi’anShaanxiChina

Background and Aims:Acetaminophen(APAP)-induced liver injury(AILI)has an increasing incidence ***,the mechanisms contributing to such liver injury are largely unknown and no targeted therapy is currently *** study aimed to investigate the effect of BTF3L4 overexpression on apoptosis and inflammation regulation in vitro and in ***:We performed a proteomic analysis of the AILI model and found basic transcription factor 3 like 4(BTF3L4)was the only outlier transcription factor overexpressed in the AILI model in ***3L4 overexpression increased the degree of liver injury in the AILI ***:BTF3L4 exerts its pathogenic effect by inducing an inflammatory response and damaging mitochondrial *** BTF3L4 expression increases the degree of apoptosis,reactive oxygen species generation,and oxidative stress,which induces cell death and liver *** damage of mitochondrial function by BTF3L4 triggers a cascade of events,including reactive oxygen species accumulation and oxidative *** to the available AILI data,BTF3L4 expression is positively associated with inflammation and may be a potential biomarker of ***:Our results suggest that BTF3L4 is a pathogenic factor in AILI and may be a potential diagnostic maker for AILI.

关键词： BTF3L4 APAP-induced liver injury Apoptosis Mitochondrial morphology Inflammation

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Potential applications of single-incision laparoscopic totally preperitoneal hernioplasty

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World Journal of Gastrointestinal surgery 2024年第7期16卷 2202-2210页

作者： Xiao-Jun Wang Ting Fei Xiong-Hua Xiang Quan Wang En-Cheng Zhou Department of Gastrointestinal surgery The First Affiliated Hospital of Ningbo UniversityNingbo 315020Zhejiang ProvinceChina Ambulatory surgery center Xijing HospitalAir Force Military Medical UniversityXi’an 710032Shaanxi ProvinceChina

BACKGROUND The totally preperitoneal(TPP)approach is a new concept that was recently *** the TPP approach combined with single-incision laparoscopic hernia repair has its own advantages,there is little evidence reflecting the characteristics and feasibility of either *** To analyze the potential applications of single-incision laparoscopic TPP(SILTPP)inguinal hernia hernioplasty for the treatment of inguinal *** A total of 152 SIL-TPP surgeries were performed at the First Affiliated Hospital of Ningbo University from February 2019 to November 2022.A single-port,named Iconport,and standard laparoscopic instruments were used during the *** data,intraoperative parameters and short-term postoperative outcomes were collected and retrospectively *** The demographic data of 152 patients underwent SIL-TPP were shown in Table *** average age was 49.5 years(range from 21 to 81 years).The average body mass index was 27.7 kg/m^(2)(range from 17.7 kg/m^(2) to 35.6 kg/m^(2)).SIL-TPP were conducted successfully in 147 *** patients were converted to the SILtransabdominal preperitoneal laparoscopic herniorrhaphy at the initial stage of the study due to a lack of *** 2 patients with incisional hernias,an auxiliary operation hole was added during the SIL-TPP procedure,as required for *** mean operative time was 64.5 minutes(range:36.0-110.0 minutes)for unilateral direct and femoral hernias and 81.6 minutes for indirect hernias(range:40.0-150.0 minutes).The mean postoperative hospital stay was 3.4 *** SIL-TPP is feasible and has advantages for inguinal hernia ***-TPP has potential benefits for patients with various abdominal wall ***,doctors should be encouraged to actively apply the TPP approach combined with a single incision in their daily work.

关键词： Totally preperitoneal hernioplasty Iconport Single incision laparoscopic Totally extraperitoneal herniorrhaphy Single incision laparoscopic totally preperitoneal hernioplasty

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Self-adaptive hydrogel for breast cancer therapy via accurate tumor elimination and on-demand adipose tissue regeneration

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Chinese Chemical Letters 2024年第1期35卷 371-378页

作者： Ran Tian Xinyu Qiu Wenyun Mu Bolei Cai Zhongning Liu Shiyu Liu Xin Chen School of Chemical Engineering and Technology Department of Chemical EngineeringShaanxi Key Laboratory of Energy Chemical Process IntensificationXi'an Jiao Tong UniversityXi'an 710049China School of Stomatology State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Clinical Research Center for Oral DiseasesDepartment of Preventive DentistryThe Fourth Military Medical UniversityXi'an 710032China School of Stomatology State Key Laboratory of Military StomatologyDepartment of Oral and Maxillofacial SurgeryThe Fourth Military Medical UniversityXi'an 710032China Department of Prosthodontics Peking University School and Hospital of StomatologyNational Clinical Research Center for Oral DiseasesNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China School of Stomatology State Key Laboratory of Military StomatologyNational Clinical Research Center for Oral DiseasesShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringThe Fourth Military Medical UniversityXi'an 710032China

The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer ***,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection *** hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed *** bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose ***,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.

关键词： Smart hydrogel with self-adaptable size Breast cancer therapy Dual responsive cargoes release Selective tumor elimination On-demand adipose tissue regeneration Effective bacteria inhibition

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The current role of dendritic cells in the progression and treatment of colorectal cancer

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Cancer Biology & Medicine 2024年第9期21卷 769-783页

作者： Yuanci Zhang Songtao Ji Ge Miao Shuya Du Haojia Wang Xiaohua Yang Ang Li Yuanyuan Lu Xin Wang Xiaodi Zhao State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers National Clinical Research Center for Digestive Diseases Xijing Hospital Fourth Military Medical University Department of Gastroenterology Tangdu Hospital Fourth Military Medical University Department of Experimental surgery Xijing Hospital Fourth Military Medical University Department of Gastroenterology the 988th Hospital of PLA Joint Logistics Support Force

Colorectal cancer(CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Dendritic cells(DCs) constitute a heterogeneous group of antigen-presenting cells that are important for initiating and regulating both innate and adaptive immune responses. As a crucial component of the immune system, DCs have a pivotal role in the pathogenesis and clinical treatment of CRC. DCs cross-present tumor-related antigens to activate T cells and trigger an antitumor immune response. However, the antitumor immune function of DCs is impaired and immune tolerance is promoted due to the presence of the tumor microenvironment. This review systematically elucidates the specific characteristics and functions of different DC subsets, as well as the role that DCs play in the immune response and tolerance within the CRC microenvironment. Moreover, how DCs contribute to the progression of CRC and potential therapies to enhance antitumor immunity on the basis of existing data are also discussed, which will provide new perspectives and approaches for immunotherapy in patients with CRC.

关键词： Colorectal cancer dendritic cells treatment strategies tumor progression

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Phospholipase A2 enzymes PLA2G2A and PLA2G12B as potential diagnostic and prognostic biomarkers in cholangiocarcinoma

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World Journal of Gastrointestinal surgery 2024年第2期16卷 289-306页

作者： Chen Qiu Yu-Kai Xiang Xuan-Bo Da Hong-Lei Zhang Xiang-Yu Kong Nian-Zong Hou Cheng Zhang Fu-Zhou Tian Yu-Long Yang center of Gallbladder Disease Shanghai East HospitalInstitute of Gallstone DiseaseSchool of MedicineTongji UniversityShanghai 200092China General surgery center Chengdu Military General HospitalChengdu 610083Sichuan ProvinceChina

BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface ***,these enzymes play a significant role in the development of diverse *** To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression *** study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and *** Set Enrichment Analysis was utilized to pinpoint associated ***,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was *** PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy *** expression of PLA2G2A was correlated with poorer overall survival in CCA ***,the study delineated pathways and miRNAs associated with these *** Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for *** increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.

关键词： PLA2G2A PLA2G12B Diagnostic Prognostic biomarkers cholangiocarcinoma

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Sorafenib sensitization in tumor therapy by iron overload and AMPK activation

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Nano Research 2024年第7期17卷 6386-6399页

作者： Jun Zhu Shoujie Zhao Yejing Zhu Shouzheng Ma Tenghui Han Fenghua Xu Huichen Li Bo Wang Zhixiong Guo Da Chen Yongquan Qu Zhimin Tian Junlong Zhao Lei Liu State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers National Clinical Research Center for Digestive DiseasesXijing HospitalFourth Military Medical UniversityXi’an 710032China Department of General surgery The Southern Theater Air Force HospitalGuangzhou 510602China Department of General surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China Department of Thoracic surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China Department of Neurology Airborne Army HospitalWuhan 430012China Key Laboratory of Modern Teaching Technology(Ministry of Education) Shaanxi Normal UniversityXi’an 710062China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Biochemistry and Molecular BiologySchool of Basic MedicineFourth Military Medical UniversityXi’an 710032China Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Medical Genetics and Developmental BiologyFourth Military Medical UniversityXi’an 710032China Department of Pediatrics Tangdu HospitalFourth Military Medical UniversityXi’an 710000China

Sorafenib,as a first-line drug for advanced hepatocellular carcinoma(HCC),could trigger ferroptosis by inhibiting cystine/glutamate ***,low-level intracellular iron and insufficient activation of adenosine monophosphate(AMP)-activated protein kinase(AMPK)confer impaired response to *** this study,a unique sorafenib nanocomposite dexterously modified with Fe-Material of Institut Lavoisier(sora@Fe-MIL)was synthesized to escalate intracellular iron level and activate AMPK,further potentiating the ferroptotic effect of ***,this strategic deployment of sora@Fe-MIL triggered an extensive demise of cancer cells,while manifesting negligible deleterious impact on normal *** prominent ferroptosis biomarkers,glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11),underwent pronounced downregulation,underscoring the efficacy of this strategy in inducing ***,the bioactivity of AMPK was considerably elevated,and its downstream targets were conspicuously inhibited by the treatment with sora@*** orthotopic HCC animal models,we observed a substantial suppression of primary in situ tumor growth,and ribonucleic acid(RNA)sequencing elucidated an elevated degree of ferroptosis and AMPK activation with the treatment of sora@*** conclusion,we proposed that the meticulously designed strategy for secure and efficacious iron release and AMPK activation could significantly potentiate the ferroptotic impact of sorafenib,thus resuscitating its therapeutic response in HCC patients.

关键词： anti-tumor ferroptosis Fe-Material of Institut Lavoisier(Fe-MIL) sorafenib adenosine monophosphate(AMP)-activated protein kinase(AMPK)

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Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma:A prospective multicenter cohort study

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 249-256页

作者： Ming-Da Wang Chen Yuan Ke-Chun Wang Nan-Ya Wang Ying-Jian Liang Hong Zhu Xiang-Min Tong Tian Yang Department of Hepatobiliary and Pancreatic surgery General Surgery CenterFirst Hospital of Jilin UniversityChangchun 130021China Department of Hepatobiliary surgery Eastern Hepatobiliary Surgery HospitalSecond Military Medical University(Naval Medical University)Shanghai 200438China Department of Clinical Laboratory Laboratory Medicine CenterZhejiang Provincial People’s HospitalHangzhou Medical CollegeHangzhou 310000China Department of Hepatobiliary surgery First Affiliated Hospital of Harbin Medical UniversityHarbin 150007China Department of Medical Oncology First Affiliated Hospital of Soochow UniversitySuzhou 215006China fDepartment of Central Laboratory Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhou 310006China

Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor *** study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor ***:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were *** were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after *** events(AEs)and toxicities were ***:A total of 409 participants were enrolled,with 206 assigned to the RSGB *** week 4,there was a trend towards improvement,but the differences were not statistically *** week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue ***,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar *** linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week *** serious drug-related AEs or toxicities were ***:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible *** findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

关键词： Cancer-related fatigue Hepatocellular carcinoma Renshenguben oral solution Efficacy Safety Ginseng

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