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Progression from ductal carcinoma in situ to invasive breast cancer:molecular features and clinical significance

Signal Transduction and Targeted Therapy 2024年第5期9卷 1841-1868页

作者： Jing Wang Baizhou Li Meng luo jia Huang Kun Zhang Shu Zheng Suzhan Zhang jiaojiao Zhou The Key Laboratory of Cancer Prevention and Intervention China National Ministry of Educationthe Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Department of Breast Surgery and Oncology the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Zhejiang Provincial Clinical Research Center for Cancer HangzhouChina Department of Pathology the Fourth Affiliated HospitalZhejiang University School of MedicineYiwuChina Department of Plastic Surgery the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Cancer Center Zhejiang UniversityHangzhouChina

Ductal carcinoma in situ(DCIS)represents pre-invasive breast carcinoma.In untreated cases,25-60%DCIS progress to invasive ductal carcinoma(IDC).The challenge lies in distinguishing between non-progressive and progressive DCIS,often resulting in over-or under-treatment in many cases.With increasing screen-detected DCIS in these years,the nature of DCIS has aroused worldwide attention.A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management.Here,we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression.We also explored the molecular features of DCIS and IDC,shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment.In addition,valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing,spatial transcriptomics and artificial intelligence,have been systematically summarized.Further,we thoroughly discussed the clinical advancements in DCIS and IDC,including prognostic biomarkers and clinical managements,with the aim of facilitating more personalized treatment strategies in the future.Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.

关键词： clinical breast alterations

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Nanomedicine Disrupts Stromal Barriers to Augment Drug Penetration for Improved Cancer Therapy

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Chinese Journal of Chemistry 2024年第10期42卷 1175-1189页

作者： Guo-Feng luo wei-Hai Chen Xian-Zheng Zhang state Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei KeyLaboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanHubei 430079China Key Laboratoryof Biomedical Polymers of Ministry of Education&Departmentof Chemistry Wuhan UniversityWuhanHubei 430072China

Tumor stroma composing diverse extracellular matrixes(ECM)and stromal cells shapes a condensed physical barrier,which severely hampers the efficient accessibility of nanomedicine to tumor cells,especially these deep-seated in the core of tumor.Such barrier significantly compromises the antitumor effects of drug-loaded nanomedicine,revealing the remarkable importance of disrupting stromal barrier for improved tumor therapy with deep penetration ability.To achieve this goal,various nanoparticle-based strategies have been developed,including direct depleting ECM components via delivering anti-fibrotic agents or targeting stromal cells to suppress ECM expression,dynamic regulation of nanoparticles’physicochemical properties(i.e.,size,surface charge,and morphology),mechanical force-driven deep penetration,natural/biomimetic self-driven nanomedicine,and transcytosis-inducing nanomedicine.All these nanostrategies were systemically summarized in this review,and the design principles for obtaining admirable nanomedicine were included.With the rapid development of nanotechnology,elaborate design of multifunctional nanomedicine provides new opportunities for overcoming the critical stromal barriers to maximize the therapeutic index of various therapies,such as chemotherapy,photodynamic therapy,and immunotherapy.

关键词： Nanomedicine Tumor stroma Deep penetration Enhanced drug perfusion Cancer therapy Drug carriers Biomaterials Nanotechnology

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Experimental study on shock interaction control of double wedge in high-enthalpy hypersonic flow subject to plasma synthetic jet

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Chinese Journal of Aeronautics 2024年第4期37卷 151-165页

作者： Xuzhen XIE Qiang LIU Yan ZHOU Zhenbing luo wei XIE Guanghui BAI Kai luo Qiu WANG jianjun WU College of Aerospace Science and Engineering National University of Defense TechnologyChangsha 410073China China Academy of Launch Vehicle Technology Beijing 100076China Institute of Mechanics Chinese Academy of SciencesBeijing 100190China

The hypersonic shock-shock interaction flow field at double-wedge geometries controlled by plasma synthetic jet actuator is experimentally studied in a Ma = 8 high-enthalpy shock tunnel with the purpose of exploring a novel technique for reducing surface heat flux in a real flight environment. The results demonstrate that increasing the discharge energy is advantageous in eliminating the shock wave, shifting the shock wave interaction point, and shortening the control response time. The oblique shock wave can be completely removed when the actuator's discharge energy grows from 0.4 J to 11.5 J, and the displacement of the shock wave interaction point increases by 124.56%, while the controlled response time is shortened by 30 μs. Besides, the reduction in diameter of the jet exit is firstly proved to have a negative impact on energy deposition in a working environment with incoming flow, which reduces the discharge energy and hence decreases the control effect. The shock wave control response time lengthens when the jet exits away from the second wedge. Along with comparing the change in wall heat flux at the second wedge over time, the control effect of plasma synthetic jet actuator with and without inflation is also analyzed. When plasma synthetic jet works in inflatable mode, both the ability to eliminate shock waves and the shifting effect of the shock wave interaction point are increased significantly, and the wall heat flux is also reduced.

关键词： Hypersonic flow High-enthalpy flow Plasma synthetic jet Shock wave Flow control

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Decreased LDHB expression in breast tumor cells causes NK cell activation and promotes tumor progression

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Cancer Biology & Medicine 2024年第6期21卷 513-540页

作者： Zhihong luo Xiaohua Huang Xinyi Xu Kefeng wei Yi Zheng Ke Gong Wenhua Li Hubei Key Laboratory of Cell Homeostasis College of Life Sciences Wuhan University Wuhan University Shenzhen Research Institute Central Laboratory University of Chinese Academy of Sciences-Shenzhen Hospital Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology School of Basic Medical Sciences Wuhan University

Objective: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B(LDHB) has been detected in breast cancer but the function of LDHB remains unknown.Methods: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer(NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell activation.Results: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers.Conclusions: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regulating immune responses and its potential as a the

关键词： Breast cancer NK cells lactate dehydrogenase B lactic acid tumor immunity

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Regulating the Electron-Deficient Component in A-DA1D-A Typed Small-Molecule Acceptors for High-Performance Organic Solar Cells

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Chinese Journal of Chemistry 2024年第6期42卷 623-630页

作者： weifei wei Ruijie Ma Zhanxiang Chen Tongle Xu Gang Li Zhenghui luo Shenzhen Key Laboratory of New Information Display and Storage Materials College of Materials Science and EngineeringShenzhen UniversityShenzhenGuangdong518060 China Department of Electronic and Information Engineering Research Institute for Smart Energy (RISE)The Hong Kong Polytechnic UniversityHung HomKowloonHong Kong999077 China

Fine-tuning of the electron-deficient unit in A-DA1D-A typed small-molecule acceptors (SMAs) plays a crucial role in developing efficient SMAs for organic solar cells (OSCs).Here,we developed a SMA based on benzo[4,5]thieno[2,3-b]quinoxaline,designated as QW1,as well as three SMAs based on 1-methylindoline-2,3-dione,identified as QW2,QW3,and QW4.Compared with QW2,QW1 displays slightly blue-shifted absorption spectra and a lower LUMO energy level due to the stronger electron-withdrawing capability of BTQx in contrast to MDO.On the other hand,the introduction of a bromine atom in QW3 and QW4 causes a blue shift in absorption and a reduction in the LUMO energy level compared to QW2.Density functional theory analysis reveals that QW1 exhibits the best molecular planarity,which endows QW1 with larger electron mobility and tighter molecular stacking.Consequently,PM6:QW1 device affords a better efficiency of 15.63% than those of the devices based on QW2 (14.25%),QW3 (13.21%) and QW4 (15.03%).Moreover,the QW4-based device yields the highest open-circuit voltage of 0.933 V,and the PM6:L8-BO:QW4 ternary device realizes a PCE of 19.03%.Overall,our work demonstrates that regulation of electron-deficient central units is an effective strategy to improve the photovoltaic performance of the resulting A-DA1D-A SMAs.

关键词： Organic solar cells Small-molecule acceptor Electron-deficient unit Energy conversion efficiency Renewable resources π-πstacking Green chemistry

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Should we perform sigmoidoscopy for colorectal cancer screening in people under 45 years?

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1248-1255页

作者： Waiian Leong jia-Qi Guo Chun Ning Fei-Fei luo Rui jiao Dong-Ye Yang Division of Gastroenterology&Hepatology The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina Department of Accident&Emergency The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina Department of Anatomical Pathology The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina Endoscopy Center The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChin

BACKGROUND The strategy for preventing colorectal cancer is screening by colonoscopy,which offers a direct way for detection and removal of adenomatous polyps(APs).American College of Gastroenterology guidelines recommend that people aged≥45 years should undergo colonoscopy;however,how to deal with people aged≤45 years is still unknown.AIM To compare the prevalence of APs and high-grade neoplasia between the left and right colon in patients≤45 years.METHODS A retrospective observational study was conducted at a single tertiary III hospital in China.This study included patients aged 18-45 years with undergoing initial colonoscopy dissection and pathological diagnosis AP or high-grade neoplasia between February 2014 and January 2021.The number of APs in the entire colon while screening and post-polypectomy surveillance in following 1-3 years were evaluated.RESULTS A total of 3053 cases were included.The prevalence of APs in the left and right colon was 55.0%and 41.6%,respectively(OR 1.7,95%CI 1.6-2.4;P3 polyps(14.1%;OR 0.3,95%CI 0.1-0.6;P<0.05).CONCLUSION This study suggests that flexible sigmoidoscopy would be an optimal approach for initial screening in people aged≤45 years and would be a more cost-effective and safe strategy.

关键词： Adenomatous polyps High-grade neoplasia Colonoscopy Flexible sigmoidoscopy

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A highly sensitive fluorescent probe RN-NA reveals peroxynitrite as a novel biomarker for primary open angle glaucoma

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 219-227页

作者： Bo Qin Yuan Lei luo Bao You-jia Zhang Ke-Yin Liu Yu-Hong Chen Department of Ophthalmology&Visual Science Eye&ENT HospitalShanghai Medical CollegeFudan UniversityShanghai 200031China Key Laboratory of Myopia NHFPC(Fudan University)Shanghai Key Laboratory of Visual Impairment and Restoration(Fudan University)Shanghai 200031China State Key Laboratory of Biobased Material and Green Papermaking Key Laboratory of Pulp&Paper Science and Technology of Shandong Province/Ministry of EducationQilu University of TechnologyShandong Academy of SciencesJinan 250353Shandong ProvinceChina

AIM:To directly quantify peroxynitrite(ONOO-)using a highly sensitive fluorescence resonance energy transfer probe RN-NA,investigate the association between ONOOand primary open angle glaucoma(POAG),and clarify whether RN-NA could be used as a potential tool for POAG diagnosis.METHODS:Plasma and aqueous humor(AH)samples were collected from POAG patients(n=100,age:59.70±6.87y)and age-related cataract(ARC)patients(n=100,age:61.15±4.60y)admitted to our hospital.Next,RN-NA was used to detect ONOO-in plasma and AH samples,and the relationship between ONOO-level and POAG was analyzed using binary logistic regression.Besides,Pearson correlation analysis was applied to characterize the correlation of the levels of ONOO-with the patients’age,intraocular pressure(IOP),and mean deviation of visual field testing.The ONOO-scavenger MnTMPyP was employed to treat the 3-morpholinosyndnomine(SIN-1)-induced ocular hypertension in mice(n=7,6-8wk).Finally,the IOP and ONOO-in both eyes were measured 30min after the last drug treatment.RESULTS:ONOO-levels of AH and plasma were significantly higher in the POAG group than in the ARC group(P<0.01).Additionally,ONOO-levels were closely correlated with POAG in a binary logistic regression analysis[odds ratio(OR)=1.008,95%confidence interval(CI):1.002-1.013,P<0.01 for AH;OR=1.004,95%CI:1.002-1.006,P<0.001 for plasma].Pearson correlation analysis showed that ONOO-levels in AH or plasma were positively associated with visual field defects(R=0.51,P<0.01 for AH;R=0.45,P<0.001 for plasma),and ONOO-levels in plasma and AH were correlated in the POAG group(R=0.69,P<0.001).However,administering MnTMPyP to mouse eyes reversed the elevated IOP caused by SIN-1(P<0.05).CONCLUSION:ONOO-levels in AH and plasma,detected by RN-NA,are significantly related to POAG and positively correlated with visual field defects in POAG patients.Hence,ONOO-is a potential biomarker of POAG,especially advanced POAG.Besides,anti-nitration compounds may be novel ocular hypotensive agents based on the animal study.

关键词： peroxynitrite fluorescent probe RN-NA primary open angle glaucoma 3-morpholinosyndnomine

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Unique landslides (loess slide-flows) induced by an extreme rainstorm in 2018 on the Loess Plateau: A new geological hazard and erosion process

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International Journal of Sediment Research 2023年第2期38卷 228-239页

作者： Li luo Wen-Zhao Guo Pei Tian Yi-li Liu Shao-Kun Wang jia-wei luo State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau/College of Water Resources and Architectural Engineering Northwest Agriculture and Forestry University State Key Laboratory of Geohazard Prevention and Geoenvironment Protection Chengdu University of Technology Key Laboratory for Geographical Process Analysis & Simulation of Hubei Province Central China Normal University

Currently, the vegetation has recovered well in most areas of the Loess Plateau in China, and soil erosion has significantly decreased. However, the heavy rainfall event in July 2018 triggered many instances of a unique type of loess landslides(i.e., slide-flows) on the gully-slopes with vegetation recovery in the Nanxiaohegou Basin on the Loess Plateau. This rainfall event was unusual and was a persistent heavy rainfall. The accumulated rainfall from 24 June to 10 July was 232.2 mm, which comprised 42% of the mean annual rainfall. A loess slide-flow is characterized by combining two movement types of the slide and flow. The loess slide-flows first slide on the gully-slopes and then turn into long run-out earthflows moving downstream, delivering vast amounts of sediment to the river. The average landslide erosion rates were 110.8-134.9 kg/m2. These loess slide-flows generally did not occur individually but in groups,which were characterized by large numbers, high density, small scale, and shallow depth. The changes of vegetation characteristics and soil characteristics both had a significant impact on the scale of the landslides. Grass with high coverage had an adverse effect on the occurrence of shallow landslides. The adverse hydrological effects of the plant may offset the weak root reinforcement. Loess slide-flows have become a new geological hazard and erosion process on the Loess Plateau. Loess slide-flows are a prominent ecological and environmental problem after vegetation restoration, and more attention should be paid to loess slide-flows in the future.

关键词： Loess plateau Landslide Soil erosion Vegetation Rainfall

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Lower extremity peripherally inserted central catheter placement ectopic to the ascending lumbar vein:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1430-1436页

作者： Xiao-Ju Zhu Ling Zhao Na Peng jia-Min luo Shui-Xia Liu Cancer Center Daping HospitalArmy Medical UniversityChongqing 400042China

BACKGROUND Peripherally inserted central catheters(PICCs)are an essential infusion route for oncology patients receiving intravenous treatments,but lower extremity veni-puncture is the preferred technique for patients with superior vena cava syndrome(SVCS).We report the case of a patient with a lower extremity PICC ectopic to the ascending lumbar vein,to indicate and verify PICC catheterisation in the lower extremity is safe and feasible.And hope to provide different per-spectives for clinical PICC venipuncture to get the attention of peers.CASE SUMMARY On 24 August 2022,a 58-year-old male was admitted to our department due to an intermittent cough persisting for over a month,which worsened 10 d prior.Imaging and laboratory investigations suggested the patient with pulmonary malignancy and SVCS.Chemotherapy was not an absolute contraindication in this patient.Lower extremity venipuncture is the preferred technique because administering upper extremity venous transfusion to patients with SVCS can exacerbate oedema in the head,neck,and upper extremities.The patient and his family were informed about the procedure,and informed consent was obtained.After successful puncture and prompt treatment,the patient was discharged,experiencing some relief from symptoms.CONCLUSION Inferior vena cava catheterisation is rare and important for cancer patients with SVCS,particularly in complex situations involving ectopic placement.

关键词： Superior vena cava syndrome Peripherally inserted central catheter Ascending lumbar vein Complications Case report

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Potential therapeutic role of spermine via Rac1 in osteoporosis:Insights from zebrafish and mice

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Zoological Research 2024年第2期45卷 367-380页

作者： Rui-Xue jiang Nan Hu Yu-wei Deng Long-wei Hu Hao Gu Nan luo Jin Wen Xin-Quan jiang Department of Prosthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China College of Stomatology Shanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai 200125China Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Preventive Dentistry Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China

Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

关键词： Osteoporosis Spermine Rac1 Zebrafish Mice

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