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High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia

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Science China(Life Sciences) 2024年第8期67卷 1635-1647页

作者： Feng-qi Liu qing-Yuan Qu ying Lei qi Chen Yu-Xiu Chen Meng-Lin Li Xue-Yan Sun Ye-Jun Wu qiu-Sha Huang Hai-Xia fu Yuan Kong Yue-ying Li qian-Fei Wang Xiao-Jun Huang Xiao-Hui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044China National Clinical Research Center for Hematologic Disease Beijing 100044China Collaborative Innovation Centre of Hematology Peking UniversityBeijing 100044China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100074China State Key Laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the *** soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP *** the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T *** contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell *** a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune ***-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of *** conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of *** may offer novel targets to develop personalized immunotherapies.

关键词： immune thrombocytopenia autoimmune diseases co-stimulatory co-inhibitory immune checkpoint CTLA4 Cytometry by Time of Flight bone marrow

Improved forecasting via physics-guided machine learning as exemplified using“21·7”extreme rainfall event in Henan

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Science China Earth Sciences 2024年第5期67卷 1652-1674页

作者： qi ZHONG Zhicha ZHANG Xiuping YAO Shaoyu HOU Shenming fu Yong CAO Linguo JING China Meteorological Administration Training Center Beijing 100081China State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesBeijing 100081China Zhejiang Meteorological Observatory Hangzhou 310017China Hebei Provincial Weather Modification Center Shijiazhuang 050020China Institute of Atmospheric Physics Chinese Academy of SciencesBeijing 100029China National Meteorological Center Beijing 100081China School of Computer Science Chengdu University of Information TechnologyChengdu 610225China

As a natural disaster,extreme precipitation is among the most destructive and influential,but predicting its occurrence and evolution accurately is very challenging because of its rarity and *** the example of the“21·7”extreme precipitation event(17–21 July 2021)in Henan Province,this study explores the potential of using physics-guided machine learning to improve the accuracy of forecasting the intensity and location of extreme *** physics-guided ways of embedding physical features,fusing physical model forecasts and revised loss function are used,i.e.,(1)analyzing the anomalous circulation and thermodynamical factors,(2)analyzing the multi-model forecast bias and the associated underlying reasons for it,and(3)using professional forecasting knowledge to design the loss function,and the corresponding results are used as input for machine learning to improve the forecasting *** results indicate that by learning the relationship between anomalous physical features and heavy precipitation,the forecasting of precipitation intensity is improved significantly,but the location is rarely adjusted and more false alarms *** reasons for this are as *** anomalous features used here mainly contain information about large-scale systems and factors which are consistent with the model precipitation deviation;moreover,the samples of extreme precipitation are sparse and so the algorithm used here is ***,by combining“good and different”multi models with machine learning,the advantages of each model are extracted and then the location of the precipitation center in the forecast is improved ***,by combining the appropriate anomalous features with multi-model fusion,an integrated improvement of the forecast of the rainfall intensity and location is ***,this study is a novel exploration to improve the refined forecasting of heavy precipitation with extreme intensity and high variability,

关键词： Extreme precipitation event Refined assessment Anomalous physical features Multi-model fusion Machine learning

Single-cell RNA sequencing reveals abnormal transcriptome signature of erythroid progenitors in pure red cell aplasia

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Genes & Diseases 2024年第1期11卷 49-52页

作者： yumei Liu Haiyue Niu Jie Ren Zhiqin Wang Li Yan Limin Xing Zonghong Shao Rong fu Zhigang Cai Huaquan Wang Department of Hematology Tianjin Medical University General HospitalTianjin 300052China School of Basic Medical Sciences Tianjin Medical UniversityTianjin 300070China

Pure red cell aplasia(PRCA)is a bone marrow failure syndrome characterized by severe anemia,reticulocytopenia,selective reduction,and even the absence of bone marrow erythroid precursors,while leukocyte and platelet counts are normal.1 Acquired PRCA can be divided into primary and *** are mediated by immune *** in the quantity and dysfunction of committed erythroid progenitors(EPs),including burst forming uniterythroid(Bfu-E)and colony forming unit-erythroid(Cfu-E),may be the source of reduced erythropoiesis and needs to be elucidated.

关键词： progenitor anemia leukocyte

Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1281-1295页

作者： Zhe-Han Bao Can Hu Yan-qiang Zhang Peng-Cheng Yu Yi Wang Zhi-Yuan Xu Huan-ying fu Xiang-dong Cheng Department of Interventional Radiology Zhejiang Cancer HospitalHangzhou 310004Zhejiang ProvinceChina Department of Gastric Surgery Zhejiang Cancer HospitalHangzhou 310022Zhejiang ProvinceChina Department of Colonic Surgery Jinhua Central HospitalJinhua 321000Zhejiang ProvinceChina Department of Breast Surgery Lin’an People’s HospitalHangzhou 311300Zhejiang ProvinceChina

BACKGROUND Gastric cancer(GC)is the fifth most common and the fourth most lethal malignant tumour in the *** patients are already in the advanced stage when they are diagnosed,which also leads to poor overall *** effect of posto-perative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local *** To investigate the safety and efficacy of a programmed cell death 1(PD-1)inhibitor combined with oxaliplatin and S-1(SOX)in the treatment of Borrmann large type III and IV *** A retrospective analysis(IRB-2022-371)was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy(NAT)from January 2020 to December *** to the different neoadjuvant treatment regimens,the patients were divided into the SOX group(61 patients)and the PD-1+SOX(P-SOX)group(28 patients).RESULTS The pathological response(tumor regression grade 0/1)in the P-SOX group was significantly higher than that in the SOX group(42.86%vs 18.03%,P=0.013).The incidence of ypN0 in the P-SOX group was higher than that in the SOX group(39.29%vs 19.67%,P=0.05).The use of PD-1 inhibitors was an independent factor affecting tumor regression ***,the use of PD-1 did not increase postoperative complications or the adverse effects of *** A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.

关键词： Neoadjuvant therapy Immunotherapy Gastric cancer Borrmann type Tumor regression grade

A nanoagent for concurrent therapy of breast cancer bone metastasis and cancer-induced bone pain through SLC7A11 interruption and photodynamic therapy

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Chinese Chemical Letters 2024年第2期35卷 295-299页

作者： qi fu Zhongming Lian Mengya Niu Yaru Huang Yanqiu Ai Long He Dandan Zhang Cuixia Zheng Jian-Jun yang Lei Wang Dandan Tian Department of Anesthesiology Pain and Perioperative MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450001China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China Translational Medical Center of Huaihe Hospital Henan UniversityKaifeng 475004China Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China

Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and *** concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are *** this study,we construct a near-infrared light-activated nano-therapeutic system to meet this *** detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs *** designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone ***,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone ***,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.

关键词： Breast cancer bone metastasis Cancer-induced bone pain Cystine/glutamate antiporter Sorafenib Photodynamic therapy

Cardiovascular toxicity with CTLA-4 inhibitors in cancer patients:A meta-analysis

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Cancer Innovation 2024年第3期3卷 49-64页

作者： Huiyi Liu Lu fu Shuyu Jin Xingdong Ye Yanlin Chen Sijia Pu yumei Xue Department of Cardiology Guangdong Cardiovascular InstituteGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongChina The Second School of Clinical Medicine Southern Medical UniversityGuangzhouGuangdongChina School of Medicine South China University of TechnologyGuangzhouGuangdongChina Guangdong Provincial Key Laboratory of Clinical Pharmacology Research Center of Medical SciencesGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongChina

Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved ***,the incidence of cardiovascular adverse events has also increased,which can affect tumor *** this study,we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor ***:Randomized clinical trials published in English from January 1,2013,to November 30,2022,were searched using the Cochrane Library and PubMed *** included trials examined all grade and grades 3–5 cardiac and vascular adverse *** involved comparisons of CTLA-4 inhibitors to placebo,CTLA-4 inhibitors plus chemotherapy to chemotherapy alone,CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone,and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target *** odds ratio(OR)and corresponding 95%confidence intervals(CIs)were calculated using the Mantel-Haenszel ***:Overall,20 trials were ***-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity(OR=1.33,95%CI:1.00–1.75,p=0.05).The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors(OR=1.73,95%CI:1.13–2.65,p=0.01),as well as the incidence rate of grades 3–5 cardiovascular adverse events(OR=2.00,95%CI:1.08–3.70,p=0.03).Compared with the non-CTLA-4 inhibitor group,CTLA-4 inhibitors plus chemotherapy,PD-1/PD-L1 inhibitors,or target agent did not significantly affect the incidence of cardiac and vascular *** incidence of grades 3–5 cardiac failure,hypertension,pericardial effusion,myocarditis,and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor,but the data were not statistically ***:Our findings suggest that the

关键词： cardiovascular toxicity CTLA-4 inhibitors malignancies

Transformation of long-period stacking ordered structures in Mg-Gd-Y-Zn alloys upon synergistic characterization of first-principles calculation and experiment and its effects on mechanical properties

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Journal of Magnesium and Alloys 2024年第5期12卷 1867-1879页

作者： Mingyu Li Guangzong Zhang Siqi Yin Changfeng Wang ying fu Chenyang Gu Renguo Guan School of Materials Science and Engineering Northeastern UniversityShenyang 110819China Key Laboratory of Near-Net Forming of Light Metals of Liaoning Province Dalian Jiaotong UniversityDalian 116028China Engineering Research Center of Continuous Extrusion Ministry of EducationDalian Jiaotong UniversityDalian 116028China Songshan Lake Materials Laboratory Dongguan 523808China

Based on experiments and first-principles calculations,the microstructures and mechanical properties of as-cast and solution treated Mg-10Gd-4Y-xZn-0.6Zr(x=0,1,2,wt.%)alloys are *** transformation process of long-period stacking ordered(LPSO)structure during solidification and heat treatment and its effect on the mechanical properties of experimental alloys are *** reveal that the stacking faults and 18R LPSO phases appear in the as-cast Mg-10Gd-4Y-1Zn-0.6Zr and Mg-10Gd-4Y-2Zn-0.6Zr alloys,*** solution treatment,the stacking faults and 18R LPSO phase transform into 14H LPSO *** Enthalpies of formation and reaction energy of 14H and 18R LPSO are calculated based on *** show that the alloying ability of 18R is stronger than that of *** reaction energies show that the 14H LPSO phase is more stable than the 18R *** elastic properties of the 14H and 18R LPSO phases are also evaluated by first-principles calculations,and the results are in good agreement with the experimental *** precipitation of LPSO phase improves the tensile strength,yield strength and elongation of the *** solution treatment,the Mg-10Gd-4Y-2Zn-0.6Zr alloy has the best mechanical properties,and its ultimate tensile strength and yield strength are 278.7 MPa and 196.4 MPa,*** elongation of Mg-10Gd-4Y-2Zn-0.6Zr reaches 15.1,which is higher than that of Mg-10Gd-4Y0.6Zr *** improving mechanism of elastic modulus by the LPSO phases and the influence on the alloy mechanical properties are also analyzed.

关键词： Mg-Gd-Y-Zn alloys Long-period stacking ordered First-principles calculations Enthalpies Mechanical properties

Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 361-369页

作者： Zhong-Xing Shi Chang-fu Li Li-Feng Zhao Zhong-qi Sun Li-Ming Cui Yan-Jie Xin dong-qing Wang Tan-Rong Kang Hui-Jie Jiang Department of Interventional Radiology the Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China Department of Digestive Medicine Daqing Longnan HospitalDaqing 163453China Department of Radiology Daqing Longnan HospitalDaqing 163453China Department of Radiology the Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China

Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment *** study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient ***:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were *** tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were *** radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was *** predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration ***:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s *** were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment *** predicted treatment response also allowed for significant discrimination of Kaplan-Meier *** Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interva

关键词： Hepatocellular carcinoma Transarterial chemoembolization Radiomics Treatment response Prediction

Inhalable metal–organic framework-mediated cuproptosis combined with PD-L1 checkpoint blockade for lung metastasis synergistic immunotherapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2281-2297页

作者： Chongzheng Yan ying Liu Guozhi Zhao Huatian yang Huaiyou Lv Genju Li Yuhan Li Yaqing fu Fengqin Sun Yafei Feng Yizhe Li Zhongxi Zhao Department of Pharmaceutics Key Laboratory of Chemical Biology of Ministry of EducationSchool of Pharmaceutical SciencesCheelloo College of MedicineShandong UniversityJinan 250012China Key University Laboratory of Pharmaceutics&Drug Delivery Systems of Shandong Province School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Cuproptosis shows enormous application prospects in lung metastasis ***,the glycolysis,Cu^(+)efflux mechanisms,and insufficient lung drug accumulation severely restrict cuproptosis ***,an inhalable poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)(OPDEA)-coated copper-based metal–organic framework encapsulating pyruvate dehydrogenase kinase 1 siRNA(siPDK)is constructed for mediating cuproptosis and subsequently promoting lung metastasis immunotherapy,namely *** inhalation,OMP shows highly efficient lung accumulation and long-term retention,ascribing to the OPDEA-mediated pulmonary mucosa *** tumor cells,OMP is degraded to release Cu2+under acidic condition,which will be reduced to toxic Cu^(+)to induce cuproptosis under glutathione(GSH)***,siPDK released from OMP inhibits intracellular glycolysis and adenosine-5ʹ-triphosphate(ATP)production,then blocking the Cu^(+)efflux protein ATP7B,thereby rendering tumor cells more sensitive to OMP-mediated ***,OMP-mediated cuproptosis triggers immunogenic cell death(ICD)to promote dendritic cells(DCs)maturation and CD8^(+)T cells ***,OMP-induced cuproptosis up-regulates membrane-associated programmed cell death-ligand 1(PD-L1)expression and induces soluble PD-L1 secretion,and thus synergizes with anti-PD-L1 antibodies(aPD-L1)to reprogram immunosuppressive tumor microenvironment,finally yielding improved immunotherapy ***,OMP may serve as an efficient inhalable nanoplatform and afford preferable efficacy against lung metastasis through inducing cuproptosis and combining with aPD-L1.

关键词： Cuproptosis Immunogenic cell death PD-L1 checkpoint blockade Copper-based metal-organic framework Immunotherapy Tumor microenvironment Transmucosal deliveryLung metastasis