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Reversal of the immunosuppressive tumor microenvironment via platinum-based neoadjuvant chemotherapy in cervical cancer

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Cancer Pathogenesis and Therapy 2024年第1期2卷 38-49页

作者： Xue Feng Xiaolin Meng Dihong Tang Shuaiqingying Guo Qiuyue Liao Jing Chen Qin Xie Fengyuan Liu Yong Fang Chaoyang Sun Yingyan Han Jihui Ai Kezhen Li Department of Gynecological Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430000China National Clinical Research Center for Obstetrics and Gynecology Cancer Biology Research Center(Key Laboratory of the Ministry of Education)Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430000China Department of Gynecologic Oncology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunan 410000China

Background Immunotherapy favors patients with tumors;however,only 3-26.3%of patients with cervical cancer benefit from single-agent immune checkpoint *** immunotherapy and chemotherapy has been explored against tumor;however,the combination remains *** study aimed to investigate the tumor immune microenvironment(TIME)and the effects of platinum-based neoadjuvant chemotherapy(NACT)in cervical cancer to identify the clinical value of combining chemotherapy with *** Multiplex immunohistochemistry(IHC)with 11 markers(cluster of differentiation[CD]3,CD8,CD4,CD11c,CD68,forkhead box P3[Foxp3],programmed cell death 1[PD-1],programmed cell death 1 ligand 1[PD-L1],indoleamine 2,3-dioxygenase[IDO],cyclin-dependent kinase inhibitor 2A[p16],and cytokeratin[CK])was performed to evaluate TIME from 108 matched pre-and post-NACT cervical cancer *** mechanism of antitumor immunity triggered by NACT was explored using RNA sequencing(RNA-seq)from four paired samples and subsequently verified in 41 samples using *** The infiltration rate of the CD8^(+)T cells in treatment-naive cervical cancer was 0.73%,and those of Foxp3^(+)regulatory T cells(Tregs)and IDO^(+)cells were 0.87%and 17.15%,***,immunoreactive T cells,dendritic cells,and macrophages were more in the stromal than the intratumor *** increased dendritic,CD3^(+)T,CD8^(+)T,and CD4^(+)T cells and decreased *** aforementioned alterations occurred predominantly in the stromal region and were primarily in ***-responders primarily showed decreased Tregs and no increase in CD8^(+)T or dendritic cell ***,dendritic cells interacted more closely with CD3^(+)T cells after NACT,an effect primarily observed in ***-seq data revealed activation of the antigen receptor-mediated signaling pathway and upregulation of major histocompatibility complex(MHC)I and MHC II after chemotherapy,validated using ***

关键词： Neoadjuvant chemotherapy Cervical cancer Tumor immune microenvironment Spatial architecture CD8 Regulatory T cells

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Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-βsignaling

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Frontiers of Medicine 2024年第1期18卷 128-146页

作者： Yuanyuan Hao Panpan Chen Shanshan Guo Mengyuan Li Xueli Jin Minghuan Zhang Wenhai Deng Ping Li Wen Lei Aibin Liang Wenbin Qian Department of Hematology The Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310009China Department of Hematology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhou450003China Key Laboratory of Laboratory Medicine Ministry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhou325000China Department of Hematology Tongji Hospital of Tongji UniversityShanghai200065China

Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.

关键词： tumor-derived exosome chimeric antigen receptor T-cell lymphoma TGF-β

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Hierarchical model updating for high-speed maglev vehicle/guideway coupled system based on multiobjective optimization

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Frontiers of Structural and Civil Engineering 2024年第5期18卷 788-804页

作者： Dexiang Li Jingyu Huang college of Civil Engineering Tongji UniversityShanghai 200092China National Maglev Transportation Engineering R&D Center Tongji UniversityShanghai 201804China

The high-speed maglev vehicle/guideway coupled model is an essential simulation tool for investigating vehicle dynamics and mitigating coupled *** improve its accuracy efficiently,this study investigated a hierarchical model updating method integrated with field ***,a high-speed maglev vehicle/guideway coupled model,taking into account the real effect of guideway material properties and elastic restraint of bearings,was developed by integrating the finite element method,multi-body dynamics,and electromagnetic levitation ***,simultaneous in-site measurements of the vehicle/guideway were conducted on a high-speed maglev test line to analyze the system response and structural modal *** the hierarchical updating,an Elman neural network with the optimal Latin hypercube sampling method was used to substitute the FE guideway model,thus improving the computational *** multi-objective particle swarm optimization algorithm with the gray relational projection method was applied to hierarchically update the parameters of the guideway layer and magnetic force layer based on the measured modal parameters and the electromagnet vibration,***,the updated coupled model was compared with the field measurements,and the results demonstrated the model’s accuracy in simulating the actual dynamic response,validating the effectiveness of the updating method.

关键词： high-speed maglev vehicle/guideway coupled model field measurement model updating neural network multi-objective optimization

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Long-term tadalafil once daily in Chinese men with erectile dysfunction:a 2-year final analysis of a post-marketing,multicenter,randomized,open-label trial

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Asian Journal of Andrology 2024年第3期26卷 282-287页

作者： Hui Jiang Lian-Ming Zhao Su Yan Ji-Hong Liu Zhao-Hui Zhu Jin-Dan Luo Yu-Tian Dai Fu-Biao Li Hao-Cheng Lin Zhi-Chao Zhang Department of Urology Peking University First HospitalBeijing 100000China Department of Urology Peking University Third HospitalBeijing 100191China Department of Urology Peking Union Medical College HospitalBeijing 100730China Department of Urology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Urology Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Urology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Departmentof Andrology Nanjing Drum Tower HospitalNanjing 210008China Department of Andrology The First Hospital of Jilin UniversityChangchun 130021China Andrology Center Department of UrologyPeking University First HospitalBeijing 100034China

The long-term safety and effectiveness of once-daily tadalafil is crucial,but limited data are available in Chinese patients witherectile dysfunction(ED).In this post-marketing,multicenter,randomized,open-label trial with 2-year follow-up,635 ED caseswere randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months,of whom 580 continued once-daily tadalafil 5 mg for21 ***-emergent adverse events in the 12-month and 24-month period were similar,with the most common beingviral upper respiratory tract infection,upper respiratory tract infection,and *** improvement from baseline inthe International Index of Erectile Function-Erectile Function(IIEF-EF)score was detected at month 12(least squares mean[LSM]change:7.9,95%confidence interval[CI]:7.5–8.4,P<0.001)and was maintained to month 24(LSM change:8.6,95%CI:8.1–9.0,P<0.001).The proportions of patients regaining normal erectile function(IIEF-EF score≥26)were 43.7%and 48.0%at months 12 and 24,*** Assessment Questionnaire results showed improved erection function in 97.5%ofpatients and improved ability to engage in sexual activity in 95.9%of patients at month 12;these values were 96.1%and 95.0%at month 24,*** quality of sexual life score based on the Sexual Life Quality Questionnaire(SLQQ)was increased by52.2%at month 12 and by 55.3%at month 24(both P<0.001).The treatment satisfaction score determined by SLQQ(mean±standard deviation)was 62.4±21.0 at month 12 versus 65.9±20.2 at month ***-year daily application of tadalafil 5mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

关键词： clinical trial erectile dysfunction long-term safety once-daily dosing tadalafil

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Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy

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World Journal of Stem Cells 2024年第6期16卷 728-738页

作者： Lin Zhu Lu He Wu Duan Bo Yang Ning Li Department of Pediatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430077Hubei ProvinceChina Division of Endocrinology Department of Internal MedicineQilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Shenzhen Research Institute of Shandong University Shenzhen 518000Guangdong ProvinceChina Institute of Organ Transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430077Hubei ProvinceChina Department of Physical Education Heze UniversityHeze 274015Shandong ProvinceChina

BACKGROUND Necrotizing enterocolitis(NEC)is a severe gastrointestinal disease that affects premature *** mounting evidence supports the therapeutic effect of exosomes on NEC,the underlying mechanisms remain *** To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell(UCMSCs)exosomes,as well as their potential in alleviating NEC in neonatal *** NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide(LPS),after which the mice received human UCMSC exosomes(hUCMSC-exos).The control mice were allowed to breastfeed with their *** tissues were collected from the mice and analyzed by histopathology and *** tissues were collected from NEC neonates and analyzed by *** biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial *** We found that autophagy is overactivated in intestinal epithelial cells during NEC,resulting in reduced expression of tight junction proteins and an increased inflammatory *** ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal *** also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by *** These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC *** findings also enhance our understanding of the role of the autophagy mechanism in NEC,offering potential avenues for identifying new therapeutic targets.

关键词： Necrotizing enterocolitis Autophagy Umbilical cord mesenchymal stem cell Exosomes Intestinal epithelial cell Intestinal barrier function

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Refined acoustic holography via nonlocal metasurfaces

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Science China(Physics,Mechanics & Astronomy) 2024年第7期67卷 113-123页

作者： Shuhuan Xie Hongyu Ma Junmei Cao Fangshuo Mo Qian Cheng Yong Li Tong Hao Institute of Acoustics School of Physics Science and EngineeringTongji UniversityShanghai 200092China Center for Spatial Information Science and Sustainable Development Applications Tongji UniversityShanghai 200092China college of Surveying and Geo-Informatics Tongji UniversityShanghai 200092China

Holography can provide the desired wavefront phase and/or amplitude for imaging,particle manipulation,bacteria trapping,and cell patterning in optics and ***,previous work on acoustic holography is mostly based on local design optimization,either using active control of the sound source or relying on the structural design to provide the desired *** precise control over the acoustic field remains a significant ***,we realize refined single-plane symmetric binary amplitude,asymmetric intensity gradient amplitude,and bi-objective hologram through the non-local holographic imaging theory that considers the acoustic coupling of structural units in *** taking into account the self-radiation and mutual radiation between many small units on a plate of well-designed thickness,as well as the transmission through the plate's apertures,we can effectively regulate the sound field behind the *** demonstrate the effectiveness of our approach through numerical simulations and experiments,showcasing a circle,a black hole,and a bi-objective with a circle and a square ***,the acoustic black hole hologram precisely reconstructs the intensity gradient distribution at two bright *** non-local holographic imaging theory is valuable for the fine-intensity regulation of the sound field and is expected to be applied in ultrasound diagnosis and treatment,medical imaging,and other fields.

关键词： acoustic holograms non-local interactions fine intensity modulation acoustic metasurfaces

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New perspectives in prognostication of hepatocellular carcinoma:The role and clinical implications of transient receptor potential family genes

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2862-2864页

作者： Shi-Hao Guan Wen-Jing Hu Xin-Yu Wang Yue-Xia Gu De-Hua Zhou Department of Plastic Surgery Qingpu Branch of Zhongshan Hospital Affiliated to Fudan UniversityShanghai 201700China Department of Nursing Shanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China Department of Thyroid Breast and Vascular SurgeryShanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China Department of Gastrointestinal Surgery Shanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China

The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and *** data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune ***,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.

关键词： Hepatocellular carcinoma Transient receptor potential channels TRPC1 gene Tumor immune microenvironment Cancer prognosis Bioinformatics in cancer research

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Interaction Mechanisms between Natural Debris Flow and Rigid Barrier Deflectors:A New Perspective for Rational Design and Optimal Arrangement

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Computer Modeling in Engineering & Sciences 2024年第5期139卷 1679-1699页

作者： Yu Huang Beilei Liu Dianlei Feng Hao Shi Department of Geotechnical Engineering College of Civil EngineeringTongji UniversityShanghai200092China Department of Hydraulic Engineering College of Civil EngineeringTongji UniversityShanghai200092China

Rigid barrier deflectors can effectively prevent overspilling landslides,and can satisfy disaster prevention ***,the mechanisms of interaction between natural granular flow and rigid barrier deflectors require further *** date,few studies have investigated the impact of deflectors on controlling viscous debris flows for geological disaster *** investigate the effect of rigid barrier deflectors on impact mechanisms,a numerical model using the smoothed particle hydrodynamics(SPH)method with the Herschel–Bulkley model is proposed to simulate the interaction between natural viscous flow and single/dual barriers with and without *** model was validated using laboratory flume test data from the ***,the model was used to investigate the influence of the deflector angle and multi-barrier *** optimal configuration of multi-barriers was analyzed with consideration to the barrier height and distance between the barriers,because these metrics have a significant impact on the viscous flow pile-up,run-up,and overflow *** investigation considered the energy dissipation process,retention efficiency,and dead-zone *** with bare barriers with similar geometric characteristics and spatial distribution,rigid barriers with deflectors exhibit superior effectiveness in preventing the overflow and overspilling of viscous debris *** for the rational design of deflectors and the optimal arrangement of multi-barriers are provided to mitigate geological disasters.

关键词： Rigid barrier deflectors deflector angle single-barrier dual-barrier arrangements viscous debris flow over-spilling delta-plus-SPH

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Predictive Value of High Mobility Group Box-1 and miR-146b in Septic Shock Patients

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Wuhan University Journal of Natural Sciences 2024年第1期29卷 85-94页

作者： FENG Jun SHAO Shasha LIU Junya PAN Yongjun YIN Huimei WANG Junshuai Department of Emergency Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030HubeiChina Department of Critical Care Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030HubeiChina Department of Critical Care Medicine Southern University of Science and Technology HospitalShenzhen 518055GuangdongChina Department of Emergency Medicine People's Hospital of Bortala Mongol Autonomous PrefectureBole 833400XinjiangChina

In the face of the elevated incidence and mortality rate of septic shock in the ICU,this retrospective study seeks to investigate the indicative and predictive value of high-mobility group box 1(HMGB1)and miR-146b in patients with septic *** RTPCR was employed in this study to quantify the HMGB1 and miR-146b levels in plasma samples obtained from the patient group and healthy *** investigation involved the comparison between the two groups and tracking changes in the patient group over *** finding revealed that upon admission,the patient group exhibited markedly elevated relative expression levels of HMGB1,which subsequently decreased over ***,the patient group displayed significantly reduced relative expression levels of miR-146b upon admission,which subsequently increased over time compared to the control *** operating characteristic(ROC)curves showed good predictive value for HMGB1 and *** experimental results suggest that HMGB1 and miR-146b serve as valuable and convenient biomarkers for evaluating the severity of septic shock and predicting ***,it is proposed that serum miR-146b may be inducible and potentially exerts a negative regulatory effect on the expression of HMGB1.

关键词： septic shock feedback loop high mobility group box-1 miR-146b disease severity

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Stress-strain relationship for reactive powder concrete with recycled powder under uniaxial compression

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Frontiers of Structural and Civil Engineering 2024年第7期18卷 1015-1027页

作者： Peng ZHU Yunming ZHU Wenjun QU Liyu XIE college of Civil Engineering Tongji UniversityShanghai 200092China Key Laboratory of Performance Evolution and Control for Engineering Structures of Ministry of Education Tongji UniversityShanghai 200092China

The recycled powder(RP)from construction wastes can be used to partially replace cement in the preparation of reactive powder *** this paper,reactive powder concrete mixtures with RP partially replacing cement,and natural sand instead of quartz,are *** curing is used,instead of steam curing that is normally requested by standard for reactive powder *** influences of RP replacement ratio(0%,10%,20%,30%),silica fume proportion(10%,15%,20%),and steel fiber proportion(0%,1%,2%)are *** effects of RP,silica fume,and steel fiber proportion on compressive strength,elastic modulus,and relative absorption energy are analyzed,and theoretical models for compressive strength,elastic modulus,and relative absorption energy are established.A constitutive model for the uniaxial compressive stress-strain relationship of reactive powder concrete with RP is *** the increase of RP replacement ratio from 0% to 30%,the compressive strength decreases by 42% and elastic modulus decreases by 24%.

关键词： recycled powder reactive powder concrete elastic modulus relative absorbed energy stress-strain relationship

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