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Zinc finger protein 831 promotes apoptosis and enhances chemosensitivity in breast cancer by acting as a novel transcriptional repressor targeting the STAT3/Bcl2 signaling pathway

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Genes & Diseases 2024年第1期11卷 430-448页

作者： Jun Fan Zhe Zhang Hongqiang Chen Dongjiao Chen Wenbo Yuan Jingzhi Li Yong Zeng Shimeng Zhou Shu Zhang Gang Zhang Jiashen Xiong Lu Zhou Jing Xu Wenbin Liu Yan Xu Department of Breast and Thyroid Surgery Daping HospitalArmy Medical University(Third Military Medical University)Chongqing 400042China Institute of Toxicology College of Preventive MedicineArmy Medical University(Third Military Medical University)Chongqing 400038China Department of Environmental Health College of Preventive MedicineArmy Medical University(Third Military Medical University)Chongqing 400038China Anesthesia and Intensive Care Chinese University of Hong KongHong Kong SAR 999077China School of Public Health Xinxiang Medical UniversityXinxiangHenan 453003China School of Public Health China Medical UniversityShenyangLiaoning 110122China

Emerging evidence suggested that zinc finger protein 831(ZNF831)was associated with immune activity and stem cell regulation in breast ***,the roles and molec-ular mechanisms of ZNF831 in oncogenesis remain ***831 expression was significantly diminished in breast cancer which was associated with promoter CpG methylation but not *** over-expression of ZNF831 suppressed breast cancer cell proliferation and col-ony formation and promoted apoptosis in vitro,while knockdown of ZNF831 resulted in an opposite ***-proliferation effect of ZNF831 was verified in *** analysis of public databases and transcriptome sequencing both showed that ZNF831 could enhance apoptosis through transcriptional regulation of the JAK/STAT *** and luciferase report assays demonstrated that ZNF831 could directly bind to one specific region of STAT3 promoter and induce the transcriptional inhibition of *** a result,the attenuation of STAT3 led to a restraint of the transcription of Bcl2 and thus accelerated the apoptotic *** of STAT3 diminished the apoptosis-promoting effect of ZNF831 in breast cancer cell ***,ZNF831 could ameliorate the anti-proliferation effect of capecitabine and gemcitabine in breast cancer cell *** findings demonstrate for the first time that ZNF831 is a novel transcriptional suppressor through inhibiting the expression of STAT3/Bcl2 and promoting the apoptosis process in breast cancer,suggesting ZNF831 as a novel biomarker and potential therapeutic target for breast cancer patients.

关键词： Apoptosis Breast cancer Chemosensitivity STAT3 ZNF831

Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles

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Bone Research 2024年第1期12卷 137-152页

作者： Weicheng Lu Jianfei Yan Chenyu Wang Wenpin Qin Xiaoxiao Han Zixuan Qin Yu Wei Haoqing Xu Jialu Gao Changhe Gao Tao Ye Franklin R.Tay Lina Niu Kai Jiao Department of Stomatology Tangdu Hospital&State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Stomatology School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina The Dental College of Georgia Augusta UniversityAugustaGAUSA

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary ***-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal *** proteins initiate inflammatory dysfunction,such as neurogenic heterotopic *** recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention ***,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two *** examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast *** relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in *** injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in *** present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.

关键词： neurogenic ossification pathogenesis

Biophysical-driven piezoelectric and aligned nanofibrous scaffold promotes bone regeneration by re-establishing physiological electrical microenvironment

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Nano Research 2024年第8期17卷 7376-7393页

作者： Aoao Wang Xinbo Ma Yafeng Yang Guoliang Shi Liwei Han Xiantong Hu Rui Shi Jun Yan Quanyi Guo Yantao Zhao Senior Department of Orthopedics the Fourth Medical Center of PLA General HospitalBeijing 100048China Department of Chemistry Capital Normal UniversityBeijing 100048China National Center for Orthopaedics Beijing Research Institute of Traumatology and OrthopaedicsBeijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China Xijing 986 hospital Department The Fourth Military Medical UniversityXi'an 710032China Institute of Orthopedics Chinese PLA General HospitalBeijing Key Laboratory of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLABeijing 100853China

The initial healing stages of bone fracture is a complex physiological process involving a series of spatially and temporally overlapping events,including pathogen clearance,immunological modulation,and *** this study,we have developed a piezoelectric and aligned nanofibrous scaffold composed of ZnO@PCL/PVDF with multiple antibacterial,immunomodulatory,and osteogenic effects using electrospinning *** scaffold’s piezoelectric signal output under ultrasound(US)control can be similar to the physiological electrical signals of healthy bone tissue,creating a truly biomimetic electrical microenvironment in the bone *** vitro studies have shown that ZnO@PCL/PVDF scaffold significantly enhances the proliferation,migration,and osteogenic differentiation of MC3T3-E1 cells under piezoelectric drive provided by ***,the scaffold exhibits inhibitory effects on the growth of *** and ***,as well as the ability to induce M2 macrophage polarization,indicating potent antibacterial and immunomodulatory *** vivo experiments demonstrated that the ZnO@PCL/PVDF scaffold can accelerate the repair of mandibular defects in rats,effectively inhibit bacterial colonization,and reduce inflammatory ***,this study confirms that the newly developed ZnO@PCL/PVDF scaffold effectively promotes bone repair by truly mimicking the endogenous electrical microenvironment and precisely regulating the temporospatial disorders of initial bone healing,thus providing a simple and effective solution for bone defects.

关键词： piezoelectricity bone defect bacterial infection ZnO nanoparticles immunomodulation osteogenesis

PVR update:pathophysiology and clinical management

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International Journal of Ophthalmology(English edition) 2024年第9期17卷 1577-1580页

作者： Peter Wiedemann Yan-Nian Hui Medical Faculty Leipzig UniversityLeipzig 04103Germany Department of Ophthalmology Eye Institute of Chinese PLAXijing HospitalFourth Military Medical UniversityXi’an 710032Shaanxi ProvinceChina

Wound-healing diseases present complex challenges,and proliferative vitreoretinopathy(PVR)has been a problem in the surgical retina for *** is a prolonged and abnormal healing response to retinal injury,such as primary retinal detachment(RD)or post-RD surgery,characterized by the formation of pre/subretinal membranes,retinal gliosis and shortening,retinal pigment epithelium cell(RPE)proliferation,and increased activity of glial cells(mainly Müller cells).

关键词： healing epithelium diseases

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain

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Science China(Life Sciences) 2024年第1期67卷 67-82页

作者： Chun-Kui Zhang Pan Wang Yuan-Yuan Ji Jian-Shuai Zhao Jun-Xiang Gu Xian-Xia Yan Hong-Wei Fan Ming-Ming Zhang Yu Qiao Xiao-Die Liu Bao-Juan Li Ming-Hui Wang Hai-Long Dong Hao-Hong Li Peng-Cheng Huang Yun-Qing Li Wu-Gang Hou Jin-Lian Li Tao Chen Department of Anatomy and K.K.Leung Brain Research Centre Fourth Military Medical UniversityXi’an 710032China Beijing Institute of Basic Medical Sciences Beijing 100850China Key Laboratory of Ministry of Public Health for Forensic Science Xi’an Jiaotong UniversityXi’an 710061China Department of Anesthesiology Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Neurosurgery the Second Affiliated Hospital of Xian Jiaotong UniversityXi’an 710004China School of Biomedical Engineering Fourth Military Medical UniversityXi’an 710032China Affiliated Mental Health Centre and Hangzhou Seventh People’s hospital Zhejiang University School of MedicineHangzhou 310013China The MOE Frontier Research Center of Brain&Brain-machine Integration Zhejiang University School of Brain Science and Brain MedicineHangzhou 310058China Department of Neurology The First Affiliated Hospital of Nanchang UniversityNanchang 330006China Department of Anatomy School of MedicineNorthwest UniversityXi’an 710069China

Chronic pain often develops severe mood changes such as ***,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely *** we found that depression-like behaviors could only be observed in 67.9%of mice with chronic neuropathic pain,leaving 32.1%of mice with depression *** determined that the spike discharges of the ventral tegmental area(VTA)-projecting lateral habenula(LHb)glutamatergic(Glu)neurons were sequentially increased in sham,resilient and susceptible mice,which consequently inhibited VTA dopaminergic(DA)neurons through a LHbGlu-VTAGABA-VTADA ***,the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic *** of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic *** study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

关键词： chronic pain depression lateral habenula ventral tegmental area dopamine susceptibility

Metformin promotes anti-tumor immunity in STK11 mutant NSCLC through AXIN1-dependent upregulation of multiple nucleotide metabolites

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Oncology Research 2024年第10期32卷 1637-1648页

作者： ZHIGUO WANG KUNLIN LI CONGHUA LU MINGXIA FENG CAIYU LIN GUOFANG YIN DAN LUO WENYI LIU KAIYU JIN YUANYAO DOU DI WU JIE ZHENG KEJUN ZHANG LI LI XIANMING FAN Department of Respiratory and Critical Care Medicine Affiliated Hospital of Southwest Medical UniversityLuzhou646000China Department of Respiratory Disease Daping HospitalArmy Medical University(Third Military Medical University)Chongqing400042China Department of Trauma Medical Center Daping HospitalState Key Laboratory of TraumaBurns and Combined InjuryArmy Medical UniversityChongqing400042China Department of Respiratory Disease People’s Hospital of Xuyong CountyLuzhou646000China Department of Outpatients Daping HospitalArmy Medical University(Third Military Medical University)Chongqing400042China

Background:Metformin has pleiotropic effects beyond glucose reduction,including tumor inhibition and immune *** enhanced the anti-tumor effects of programmed cell death protein 1(PD-1)inhibitors in serine/threonine kinase 11(STK11)mutant non-small cell lung cancer(NSCLC)through an axis inhibition protein 1(AXIN1)-dependent ***,the alterations of tumor metabolism and metabolites upon metformin administration remain ***:We performed untargeted metabolomics using liquid chromatography(LC)-mass spectrometry(MS)/MS system and conducted cell experiments to verify the results of bioinformatics ***:According to the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database,most metabolites were annotated into metabolism,including nucleotide ***,the differentially expressed metabolites in H460(refers to H460 cells),H460_met(refers to metformin-treated H460 cells),and H460_KO_met(refers to metformin-treated Axin1-/-H460 cells)were distributed into six clusters based on expression *** clusters with a reversed expression pattern upon metformin treatment were selected for further *** screened out metabolic pathways through KEGG pathway enrichment analysis and found that multiple nucleotide metabolites enriched in this pathway were ***,these metabolites enhanced the cytotoxicity of activated T cells on H460 cells in vitro and can activate the stimulator of the interferon genes(STING)pathway independently of ***:Relying on AXIN1,metformin upregulated multiple nucleotide metabolites which promoted STING signaling and the killing of activated T cells in STK11 mutant NSCLC,indicating a potential immunotherapeutic strategy for STK11 mutant NSCLC.

关键词： Metformin Serine/threonine kinase 11(STK11) Lung cancer Axis inhibition protein 1(AXIN1) Nucleotide metabolites

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

Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression

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Frontiers of Medicine 2024年第3期18卷 430-445页

作者： Yue Ma Hongwei Lv Fuxue Xing Wei Xiang Zixin Wu Qiyu Feng Hongyang Wang Wen Yang Cancer Research Center First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei230027China National Center for Liver Cancer Naval Medical University(Second Military Medical University)Shanghai201805China International Co-operation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery HospitalNaval Medical University(Second Military Medical University)Shanghai200438China Shanghai Key Laboratory of Hepato-biliary Tumor Biology Shanghai200438China Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer Ministry of EducationShanghai200438China

Crosstalk between cancer cells and the immune microenvironment is determinant for liver cancer progression.A tumor subpopulation called liver cancer stem cells(CSCs)significantly accounts for the initiation,metastasis,therapeutic resistance,and recurrence of liver *** evidence demonstrates that the interaction between liver CSCs and immune cells plays a crucial role in shaping an immunosuppressive microenvironment and determining immunotherapy *** review sheds light on the bidirectional crosstalk between liver CSCs and immune cells for liver cancer progression,as well as the underlying molecular mechanisms after presenting an overview of liver CSCs characteristic and their ***,we discuss the potential application of liver CSCs-targeted immunotherapy for liver cancer treatment.

关键词： liver cancer cancer stem cell immune cell immunotherapy

Long-and short-term outcomes for resectable gallbladder carcinoma patients treated with curative-intent laparoscopic versus open resection:a multicenter propensity score-matched comparative study

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Hepatobiliary Surgery and Nutrition 2024年第5期13卷 788-800,I0002页

作者： Zhi-Peng Liu Xing-Xing Su Long-Fei Chen Xue-Lei Li Yi-Shi Yang Zhi-Long You Xiao-Lin Zhao Fan Huang Chao Yu Zhao-Ping Wu Wei Chen Jin-Xue Zhou Wei Guo Da-Long Yin Ping Yue Rui Ding Yi Zhu Wei Chen Yan Jiang Jie Bai Jing-Jing Wang Yan-Qi Zhang Dong Zhang Hai-Su Dai Wan Yee Lau Zhi-Yu Chen The Biliary Surgery Branch of Elite Group of Chinese Digestive Surgery(EGCDS) Department of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)ChongqingChina Hepato-pancreato-biliary Center Tsinghua Changgung HospitalTsinghua UniversityBeijingChina Department of General Surgery Third Affiliated Hospital of Zunyi Medical UniversityZunyiChina Department of General Surgery First Affiliated Hospital of Anhui Medical UniversityHefeiChina Department of Hepatobiliary Surgery Affiliated Hospital of Guizhou Medical UniversityGuiyangChina Department of Hepatopancreatobiliary Surgery Jiujiang First People’s HospitalJiujiangChina Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Department of Hepatopancreatobiliary Surgery Henan Provincial Tumor HospitalZhengzhouChina Department of General Surgery Capital Medical University Affiliated Beijing Friendship HospitalBeijingChina Department of Hepatobiliary Surgery First Affiliated Hospital of USTCHefeiChina Department of General Surgery Lanzhou University First Affiliated HospitalLanzhouChina Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Air Force Medical UniversityXi’anChina Department of Hepatopancreatobiliary Surgery The Second Affiliated Hospital Zhejiang University School of MedicineHangzhouChina Department of Health Statistics College of Military Preventive MedicineThird Military Medical University(Army Medical University)ChongqingChina Department of Hepatobiliary Surgery First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina Faculty of Medicine the Chinese University of Hong KongHong KongChina 不详

Background:Gallbladder cancer(GBC)was once considered a contraindication for laparoscopic surgery,but it is becoming more common to use laparoscopic surgery for GBC *** aim of this study was to analyze the long-and short-term outcomes of patients with more advanced T-staged GBC treated with curative intent as defined by the National Comprehensive Cancer Network(NCCN)after laparoscopic resection(LR)versus open resection(OR).Methods:A multicenter database was used to select consecutive GBC patients treated with curative-intent resection as defined by the NCCN between 2016 and *** patients were divided into the LR group and the OR *** score matching(PSM)was used to eliminate selection *** endpoints were overall survival(OS),progression-free survival(PFS),and short-term *** factors that were independently associated with OS and PFS were ***:Of 626 GBC patients treated with curative-intent resection,after PSM,51 patients were in the LR group and 153 patients were in the OR *** LR group had more patients who were suitable to receive adjuvant chemotherapy(AC),a longer operation time,more harvested lymph nodes,and a lower overall morbidity *** rates of OS and PFS were not significantly different between the two *** was independently associated with better OS and ***:The overall morbidity of GBC patients after LR was lower,but the long-term outcomes between LR and OR were not significantly *** GBC patients treated with LR were more likely to receive AC,and the use of AC after curative-intent resection of GBC helped achieve better long-term survival outcomes.

关键词： Gallbladder cancer(GBC) laparoscopic resection(LR) morbidity survival adjuvant chemotherapy(AC)