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Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2748-2760页

作者： Hua-yang Fan Ming-da Zhao Hong-jie Jiang Zhen-wei Yu Yu-jiang Fan Xin-hua Liang Ya-ling Tang Yong Sun State Key Laboratory of Oral Diseases&National Center for Stomatology&National clinical research Center for Oral Diseases&Department of Oral and Maxillofacial Surgery West China Hospital of StomatologySichuan UniversityChengdu 610041China National Engineering research Center for Biomaterials Sichuan UniversityChengdu 610065China State Key Laboratory of Oral Diseases&National Center for Stomatology&National clinical research Center for Oral Diseases&Department of Oral Pathology West China Hospital of StomatologySichuan UniversityChengdu 610041China

Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC *** analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC ***-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p ***-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC *** results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC ***,we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC *** findings provide a new perspective for the development of OSCC treatments.

关键词： Oral squamous cell carcinoma CircRNA MiRNA sponge Antagomir MiRNA delivery Cisplatin-based nanoparticles Drug delivery systems Tumor elimination

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SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aβ generation

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Zoological research 2024年第4期45卷 845-856页

作者： Qunxian Wang Yanshuang Jiang Zijun Meng Xiangjun Dong Dongjie Hu Liangye Ji Weihui Zhou Weihong Song Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400000China Second Affiliated hospital and Yuying Children’s hospital Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325001China

SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains *** this study,the role of SIL1 in APP processing was explored both in vitro and in *** the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant *** the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type *** blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant *** indicated that SIL1 expression decreased in APP23/PS45 *** of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in ***,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 ***,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 ***,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 *** findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.

关键词： Alzheimer’s disease SIL1 APP processing Cognitive impairment

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Present situation of minimally invasive surgical treatment for early gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1154-1165页

作者： Chun-Yan Li Yi-Feng Wang Li-Kang Luo Xiao-Jun Yang The First clinical Medical School Lanzhou UniversityLanzhou 730000Gansu ProvinceChina The First clinical Medicine College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina General Surgery clinical Centre Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina The Second Department of General Surgery Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Lanzhou University People's clinical hospital Lanzhou 730000Gansu ProvinceChina Gansu research Center of Prevention and Control Project for Digestive Oncology Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Gansu Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

Minimally invasive surgery is a kind of surgical operation,which is performed by using professional surgical instruments and equipment to inactivate,resect,repair or reconstruct the pathological changes,deformities and wounds in human body through micro-trauma or micro-approach,in order to achieve the goal of treatment,its surgical effect is equivalent to the traditional open surgery,while avoiding the morbidity of conventional surgical *** addition,it also has the advantages of less trauma,less blood loss during operation,less psychological burden and quick recovery on patients,and these minimally invasive techniques provide unique value for the examination and treatment of gastric cancer *** minimally invasive surgical techniques have developed rapidly and offer numerous options for the treatment of early gastric cancer(EGC):endoscopic mucosal resection(EMR),underwater EMR(UEMR),endoscopic submucosal dissection(ESD),endoscopic full-thickness resection(EFTR),endoscopic submu-cosal excavation(ESE),submucosal tunnel endoscopic resection,laparoscopic and endoscopic cooperative surgery(LECS);Among them,EMR,EFTR and LECS technologies have a wide range of applications and different modific-ations have been derived from their respective surgical operations,such as band-assisted EMR(BA-EMR),conven-tional EMR(CEMR),over-the-scope clip-assisted EFTR,no-touch EFTR,the inverted LECS,closed LECS,and so *** new and improved minimally invasive surgeries are more precise,specific and effective in treating different types of EGC.

关键词： Minimally invasive surgery Early gastric cancer Endoscopic mucosal resection Endoscopic full-thickness resection Laparoscopic and endoscopic cooperative surgery

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A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease

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Neural Regeneration research 2024年第8期19卷 1828-1834页

作者： Yongjiang Zhang Shiyi Yin Run Song Xiaoyi Lai Mengmeng Shen Jiannan Wu Junqiang Yan Key Laboratory of Neuromolecular Biology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains ***-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains *** kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum *** is regulated by PERK and is a target of the unfolded protein *** is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh *** this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s *** used adeno-associated virus to knockdown PHB2 *** res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s *** rexpression of PHB2 inhibited these *** also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s *** found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted *** addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of *** findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.

关键词： endoplasmic reticulum dopaminergic neuron microtubule-associated protein 1 light chain 3 mitophagy oxidative stress Parkin Parkinson’s disease PKR-like endoplasmic reticulum kinase reactive oxygen species prohibitin-2

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Mission of the National Cancer Center hospital in Japan to promote clinical trials for precision medicine

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Cancer Biology & Medicine 2024年第1期21卷 1-3页

作者： Kazuaki Shimada Kenichi Nakamura Noboru Yamamoto Department of Hepatobiliary and Pancreatic Surgery National Cancer Center HospitalTokyo 104-0045Japan clinical research Support Offce National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan

Precision medicine is a growing field *** its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical *** main obstacles are associated... 详细信息

关键词： clinical Cancer overcome

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Expert consensus on pediatric orthodontic therapies of malocclusions in children

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International Journal of Oral Science 2024年第2期16卷 186-196页

作者： Chenchen Zhou Peipei Duan Hong He Jinlin Song Min Hu Yuehua Liu Yan Liu Jie Guo Fang Jin Yang Cao Lingyong Jiang Qingsong Ye Min Zhu Beizhan Jiang Wenhua Ruan Xiao Yuan Huang Li Rui Zou Yulou Tian Li Gao Rui Shu Jianwei Chen Renkai Liu Shujuan Zou Xiaobing Li State Key Laboratory of Oral Diseases&National Center for Stomatology&National clinical research Center for Oral Diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National clinical research Center for Oral Diseases&Department of Orthodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&Key Laboratory of Oral Biomedicine Ministry of Education&Hubei Key Laboratory of Stomatology&Department of Orthodontics&Center for Dentofacial development and Sleep Medicine School and Hospital of StomatologyWuhan UniversityWuhanChina Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences&Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education Stomatological Hospital of Chongqing Medical UniversityChongqing Medical University&College of StomatologyChongqing Medical UniversityChongqingChina Department of Orthodontics Hospital of StomatologyJilin UniversityChangchunChina Department of Orthodontic&Oral Biomedical Engineering Laboratory Shanghai Stomatological HospitalFudan UniversityShanghaiChina Department of Orthodontics Central LaboratoryPeking University School and Hospital for Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical Devices&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental Materials&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Department of Orthodontics School and Hospital of StomatologyCollege of MedicineShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in *** its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these *** intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the *** orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition *** an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social *** consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early *** elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

关键词： permanent stated children

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Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors

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World Journal of Diabetes 2024年第1期15卷 53-71页

作者： Min Wang Yang Ou Xiang-Lian Yuan Xiu-Fang Zhu Ben Niu Zhuang Kang Bing Zhang Anwar Ahmed Guo-Qiang Xing Heng Su School of Chemical Science and Technology Yunnan UniversityKunming 650091Yunnan ProvinceChina Department of Endocrinology The First People’s Hospital of Yunnan ProvinceKunming 650032Yunnan ProvinceChina clinical Laboratory Nanchong Central Hospital&The Second Clinical Medical College of North Sichuan Medical UniversityNanchong 637000Sichuan ProvinceChina Department of Preventive Medicine and Biostatistics Uniformed Services University of the Health SciencesBethesdaMD 20814United States The Affiliated hospital and Second clinical Medical College North Sichuan Medical UniversityNanchong 637000Sichuan ProvinceChina Department of research and development Lotus *** LLCGaithersburgMD 20878United States

BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention *** branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amino acids(AAAs:Tyrosine,tryptophan,phenylalanine)show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical ***,improvement is needed to support its clinical *** To evaluate the effects of body mass index(BMI)and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body *** Ninety-seven new-onset T2DM patients(hospital of Yunnan Province,Kunming,China,were ***-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/*** Fasting serum AAAs,BCAAs,glutamate,and alanine were greater and high-density lipoprotein(HDL)was lower(P<0.05,each)in OB-T2DM patients than in NW-T2DM patients,especially in male OB-T2DM ***,histidine,leucine,methionine,and lysine were greater in male patients than in female ***,histidine,alanine,glutamate,lysine,valine,methionine,leucine,isoleucine,tyrosine,phenylalanine,and tryptophan were significantly correlated with abdominal adiposity,body weight and BMI,whereas isoleucine,leucine and phenylalanine were negatively correlated with *** Heterogeneously elevated amino acids,especially BCAAs/AAAs,across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM *** higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals,whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW *** potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to

关键词： Hyperaminoacidemia Branched-chain/aromatic amino acids New-onset type-2 diabetes Predictor Obesity Sex

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Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin Medical research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational Medical Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Department of Neuro-Intensive Care unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

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Early-onset and later-onset cancer: trends, risk factors, and prevention in Northern China: a prospective study

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Science China Life Sciences 2024年

作者： Tong Liu Chen-An Liu Qing-Song Zhang Qi Zhang Yi-Ming Wang Meng-Meng Song Shi-Qi Lin Li Deng Shou-Ling Wu Han-Ping Shi Department of Gastrointestinal Surgery Department of Clinical Nutrition Beijing Shijitan Hospital Capital Medical University National clinical research Center for Geriatric Diseases Xuanwu Hospital Capital Medical University Key Laboratory of Cancer FSMP for State Market Regulation Laboratory for clinical Medicine Capital Medical University Department of General Surgery Kailuan General Hospital Department of Genetics Yale School of Medicine Department of Hepatobiliary Surgery Kailuan General Hospital Cardiovascular research Institute University of California Department of Cardiology Kailuan General Hospital

The characteristics of early-onset(onset age <50 years) and later-onset(onset age ≥50 years) cancers differ significantly. Identifying novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for reducing its burden. This study aimed to analyze the trends in incidence and risk factors for early-onset and late-onset cancers. We conducted a prospective study by drawing data from the Kailuan Study. This study included 6,741 participants with cancer(624 with early-onset cancer and 6,117 with later-onset cancer)and 6,780 matched controls among the 186,249 participants who underwent Kailuan health examinations from 2006 to 2019. The primary outcomes were cancer incidence rates, and associated risk factors for early-and later-onset cancer. Weighted Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early-and later-onset cancer by cancer type. Populationattributable risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the population. Except for liver cancer, incidence rates for nearly all types of cancer increased during the study period. Smoking, alcohol consumption, lipid metabolism disorders, hypertension, diabetes mellitus, fatty liver, and inflammation were associated with a significantly increased risk of cancer at multiple sites, but risk factors for cancer incidence differed by site. Smoking, alcohol consumption, inflammation,and hypertension were the major contributors to preventable cancer. The incidence of several different types of cancer, including earlyonset cancer, is increasing in northeastern China. Differences in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.

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Nanomedicine integrating the lipidic derivative of 5-fluorouracil,miriplatin and PD-L1 si RNA for enhancing tumor therapy

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Chinese Chemical Letters 2024年第6期35卷 385-391页

作者： An Lu Yuhao Guo Yi Yan Lin Zhai Xiangyu Wang Weiran Cao Zijie Li Zhixia Zhao Yujie Shi Yuanjun Zhu Xiaoyan Liu Huining He Zhiyu Wang Jian-Cheng Wang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Tianjin Key Laboratory on Technologies Enabling development of clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China Department of Immuno-oncology The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011China Department of Pharmacy Clinical Trial Research CenterChina-Japan Friendship HospitalBeijing 100029China Laboratory of innovative formulations and pharmaceutical excipients Ningbo Institute of Marine MedicinePeking UniversityNingbo 315832China

Immunosuppressive microenvironments present critical problems in clinical *** regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied *** this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into Lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for *** vitro results showed that Lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by ***,in vivo results revealed that LipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint *** Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.

关键词： Chemo-immunotherapy Immune checkpoint inhibition Gene silencing Miriplatin Macrophage phagocytosis Nanotechnology

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