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Dendritic cells engineered to secrete anti-Dc R3 antibody augment cytotoxic T lymphocyte response against pancreatic cancer in vitro

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World Journal of Gastroenterology 2017年第5期23卷 817-829页

作者： Jiang Chen Xiao-Zhong Guo Hong-Yu Li Jia-Jun Zhao wen-da xu Department of Gastroenterology Shenyang General Hospital of PLAShenyang 110016Liaoning ProvinceChina

AIM To investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer(PC) in vitro induced by dendritic cells(DCs) engineered to secrete anti-DcR 3 monoclonal antibody(mA b).METHODS DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-Dc R3 monoclonal antibody heavy and light chain m RNA and/or total tumor RNA(DC-tumor-anti-Dc R3 RNA or DC-total tumor RNA) by using electroporation technology. The identification, concentration and function of anti-DcR 3 mA b secreted by DC-tumor-anti-Dc R3 RNA were determined by western blotting and enzyme-linked immunosorbent assay. After co-culturing of autologous isolated PC cells with target DCs, the effects of secreting anti-DcR 3 mA b on RNA-DCs' viability and apoptosis were assessed by MTT assay and flow cytometry. Analysis of enhanced antigen-specific immune response against PC induced by anti-DcR 3 mA b secreting DCs was performed using a 51 Cr releasing test. T cell responses induced by RNAloaded DCs were analyzed by measuring cytokine levels, including IFN-γ, IL-10, IL4, TNF-α and IL-12.RESULTS The anti-Dc R3 m Ab secreted by DCs reacted withrecombinant human Dc R3 protein and generated a band with 35 k da molecular weight. The secreting m Ab was transient, peaking at 24 h and becoming undetectable after 72 h. After co-incubation with DCtumor-anti-Dc R3 RNA for designated times, the Dc R3 level in the supernatant of autologous PC cells was significantly down-regulated(P < 0.05). DCs secreting anti-Dc R3 m Ab could improve cell viability and slow down the apoptosis of RNA-loaded DCs, compared with DC-total tumor RNA(P < 0.01). The anti-Dc R3 m Ab secreted by DC-tumor-anti-Dc R3 RNA could enhance the induction of cytotoxic T lymphocytes(CTLs) activity toward RNA-transfected DCs, primary tumor cells, and PC cell lines, compared with CTLs stimulated by DC-total tumor RNA or control group(P < 0.05). Meanwhile, the antigen-specific CTL responses were MHC class I-restricted. The CD4+ T

关键词：树枝状的房间编码抗体的 RNA DcR3 细胞毒素的 T 淋巴细胞反应胰腺的癌症

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Nonlinear Extrapolation Estimates of π

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Acta Mathematicae Applicatae Sinica 2024年第1期40卷 91-108页

作者： wen-qing xu Sha-sha Wang da-chuan xu Beijing Institute for Scientific and Engineering Computing Beijing University of TechnologyBeijing100124China Department of Mathematics and Statistics California State UniversityLong BeachCalifornia90840USA Department of Mathematics and Physics Shijiazhuang Tiedao UniversityShijiazhuang050043China

The classical Archimedean approximation of π uses the semiperimeter or area of regular polygons inscribed in or circumscribed about a unit circle in R~2 and it is well-known that by using linear combinations of these basic estimates,modern extrapolation techniques can greatly speed up the approximation process.Similarly,when n vertices are randomly selected on the circle,the semiperimeter and area of the corresponding random inscribed and circumscribing polygons are known to converge to π almost surely as n→∞,and by further applying extrapolation processes,faster convergence rates can also be achieved through similar linear combinations of the semiperimeter and area of these random polygons.In this paper,we further develop nonlinear extrapolation methods for approximating π through certain nonlinear functions of the semiperimeter and area of such polygons.We focus on two types of extrapolation estimates of the forms χ_n=S_n~αA_n~β and Y_n(p)=(αS_n~p+βA_n~p)~(1/p) where α+β=1,p≠0,and Sn and An respectively represents the semiperimeter and area of a random n-gon inscribed in the unit circle in R~2,and Xn may be viewed as the limit of Y_n(p) when p→0.By deriving probabilistic asymptotic expansions with carefully controlled error estimates for Xn and Y_n(p),we show that the choice α=4/3,β=-1/3 minimizes the approximation error in both cases,and their distributions are also asymptotically normal.

关键词： Archimedean polygons random polygons approximations ofπ extrapolation processes asymptotic convergence

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Restrictive vs liberal transfusion for upper gastrointestinal bleeding:A meta-analysis of randomized controlled trials

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World Journal of Gastroenterology 2013年第40期19卷 6919-6927页

作者： Juan Wang Yong-Xin Bao Ming Bai Yong-Guo Zhang wen-da xu Xing-Shun Qi Department of Gastroenterology No. 463 Hospital of Chinese PLA Post-doctoral Research Station Shenyang General Hospital of Chinese PLA Xijing Hospital of Digestive Diseases Fourth Military Medical University Department of Gastroenterology Shenyang General Hospital of Chinese PLA

AIM:To compare the outcome of upper gastrointestinal bleeding(UGIB) between patients receiving restrictive and liberal transfusion.METHODS:PubMed,EMBASE,and Cochrane Library databases were employed to identify all relevant randomized controlled trials regarding the outcome of UGIB after restrictive or liberal transfusion. Primary outcomes were death and rebleeding. Secondary outcomes were length of hospitalization,amount of blood transfused,and hematocrit and hemoglobin at discharge or after expansion.RESULTS:Overall,4 papers were included in this meta-analysis. The incidence of death was significantly lower in patients receiving restrictive transfusion than those receiving liberal transfusion(OR:0.52,95%CI:0.31-0.87,P = 0.01). The incidence of rebleeding was lower in patients receiving restrictive transfusion than those receiving liberal transfusion,but this difference did not reach any statistical significance(OR:0.26,95%CI:0.03-2.10,P = 0.21). Compared with those receiving liberal transfusion,patients receiving restrictive transfusion had a significantly shorter length of hospitalization(standard mean difference:-0.17,95%CI:-0.30--0.04,P = 0.009) and a significantly smaller amount of blood transfused(standard mean difference:-0.74,95%CI:-1.15--0.32,P = 0.0005) with a lower hematocrit and hemoglobin level at discharge or after expansion.CONCLUSION:Restrictive transfusion should be employed in patients with UGIB.

关键词： Upper gastrointestinal bleeding Blood transfusion Meta-analysis Randomized controlled trial

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Nonselective beta-blockers in cirrhotic patients with no or small varices:A meta-analysis

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World Journal of Gastroenterology 2015年第10期21卷 3100-3108页

作者： Xing-Shun Qi Yong-Xin Bao Ming Bai wen-da xu Jun-Na dai Xiao-Zhong Guo Liver cirrhosis group Department of GastroenterologyGeneral Hospital of Shenyang Military Area Xijing Hospital of Digestive Diseases Fourth Military Medical University Department of Traditional Medicine General Hospital of Shenyang Military Area

AIM:To explore effects of nonselective beta-blockers(NSBBs) in cirrhotic patients with no or small varices.METHODS:The Pub Med,EMBASE,Science Direct,and Cochrane library databases were searched for relevant papers.A meta-analysis was performed using ORs with 95%CI as the effect sizes.Subgroup analysis was conducted according to the studies including patients without varices and those with small varices.RESULTS:Overall,784 papers were initially retrieved from the database searches,of which six randomized controlled trials were included in the meta-analysis.The incidences of large varices development(OR = 1.05,95%CI:0.25-4.36;P = 0.95),first upper gastrointestinal bleeding(OR = 0.59,95%CI:0.24-1.47;P = 0.26),and death(OR = 0.70,95%CI:0.45-1.10;P = 0.12) were similar between NSBB and placebo groups.However,the incidence of adverse events was significantly higher in the NSBB group compared with the placebo group(OR = 3.47,95%CI:1.45-8.33;P = 0.005).The results of subgroup analyses were similar to those of overall analyses.CONCLUSION:The results of this meta-analysis indicate that NSBBs should not be recommended for cirrhotic patients with no or small varices.

关键词： Beta-blocker Liver cirrhosis Portal hyper-tension

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Design and performance evaluation of a large field-of-view dual-particle time-encoded imager based on a depth-of-interaction detector

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Nuclear Science and Techniques 2024年第4期35卷 1-14页

作者： Dong Zhao xu-wen Liang Ping-Kun Cai Wei Cheng wen-Bao Jia da-Qian Hei Qing Shan Yong-Sheng Ling Chao Shi Department of Nuclear Science and Technology Nanjing University of Aeronautics and AstronauticsNanjing 211106China Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Suzhou 215000China School of Nuclear Science and Technology Lanzhou UniversityLanzhou 730000China

Time-encoded imaging is useful for identifying potential special nuclear materials and other radioactive sources at a distance.In this study,a large field-of-view time-encoded imager was developed for gamma-ray and neutron source hotspot imaging based on a depth-of-interaction(DOI)detector.The imager primarily consists of a DOI detector system and a rotary dual-layer cylindrical coded mask.An EJ276 plastic scintillator coupled with two SiPMs was designed as the DOI detector to increase the field of view and improve the imager performance.The difference in signal time at both ends and the log of the signal amplitude ratio were used to calculate the interaction position resolution.The position resolution of the DOI detector was calibrated using a collimated Cs-137 source,and the full width at half maximum of the reconstruction position of the Gaussian fitting curve was approximately 4.4 cm.The DOI detector can be arbitrarily divided into several units to independently reconstruct the source distribution images.The unit length was optimized via Am-Be source-location experiments.A multidetector filtering method is proposed for image denoising.This method can effectively reduce image noise caused by poor DOI detector position resolution.The vertical field of view of the imager was(-55°,55°)when the detector was placed in the center of the coded mask.A DT neutron source at 20 m standoff could be located within 2400 s with an angular resolution of 3.5°.

关键词： Time-encoded imager Depth-of-interaction detector Dual-particle imaging Hotspot imaging

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Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance

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中华医学杂志(英文版) 2024年第7期137卷 859-870页

作者： Wang Xianlong Zhao Chuan Lin Jincheng Liu Hongxing Zeng Qiuhong Chen Huadong Wang Ye xu dapeng Chen wen xu Moping Zhang En Lin da Lin Zhixiong Sanbo Brain Hospital Capital Medical University Beijing 100093 Department of Bioinformatics School of Medical Technology and Engineering Key Laboratory of Medical Bioinformatics Key Laboratory of Ministry of Education for Gastrointestinal Cancer Fujian Medical University Fuzhou Fujian 350122 China Department of Neurosurgery

Background: Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods: Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results: Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox,P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group (P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB (P = 0.01).Conclusions: ACP comprises three molecular subtypes with disti

关键词： Craniopharyngioma Central nervous system tumor Precision medicine beta Catenin Proto-Oncogene Proteins B-raf

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Sulfation of chondroitin and bile acids converges to antagonize Wnt/β-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1241-1256页

作者： Pengfei xu Yue Xi Jong-Won Kim Junjie Zhu Min Zhang Meishu xu Songrong Ren da Yang Xiaochao Ma wen Xie Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Department of Hepatobiliary and Pancreatic Surgery Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Department of Pharmacology&Chemical Biology University of PittsburghPittsburghPA 15261USA

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology.3’-Phosphoadenosine 5’-phosphosulfate(PAPS)synthase 2(PAPSS2)is the primary enzyme to generate the universal sulfonate donor PAPS.The involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli(APC)mutation-promoted colonic carcinogenesis has not been reported.Here,we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages,and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon cancer.Gut epithelial-specific heterozygous Apc deficient and Papss2-knockout(Apc^(Δgut-Het)Papss2^(Δgut))mice were created,and the phenotypes were compared to the spontaneous intestinal tumorigenesis of Apc^(Δgut-Het)mice.Apc^(Δgut-Het)Papss2^(Δgutmice) were more sensitive to gut tumorigenesis,which was mechanistically accounted for by the activation of Wnt/β-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor(FXR)-transducin-like enhancer of split 3(TLE3)gene regulatory axis.Chondroitin sulfate supplementation in Apc^(Δgut-Het)Papss2^(Δgutmice) alleviated intestinal tumorigenesis.In summary,we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids-FXR-TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin signaling.Chondroitin sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

关键词： Colon cancer APC Wnt/b-catenin PAPSS2 Chondroitin sulfate Sulfation Bile acids FXR

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Unconditionally stable Crank-Nicolson algorithm with enhanced absorption for rotationally symmetric multi-scale problems in anisotropic magnetized plasma

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Journal of Systems Engineering and Electronics 2024年第1期35卷 65-73页

作者： wen Yi WANG Junxiang xu Hongbing School of Automatic Engineering University of Electronic Science and Technology of ChinaChengdu 611731China Beijing Institute of Aerospace Systems Engineering Beijing 100076China

Large calculation error can be formed by directly employing the conventional Yee’s grid to curve surfaces.In order to alleviate such condition,unconditionally stable CrankNicolson Douglas-Gunn(CNDG)algorithm with is proposed for rotationally symmetric multi-scale problems in anisotropic magnetized plasma.Within the CNDG algorithm,an alternative scheme for the simulation of anisotropic plasma is proposed in body-of-revolution domains.Convolutional perfectly matched layer(CPML)formulation is proposed to efficiently solve the open region problems.Numerical example is carried out for the illustration of effectiveness including the efficiency,resources,and absorption.Through the results,it can be concluded that the proposed scheme shows considerable performance during the simulation.

关键词： anisotropic magnetized plasma body-of-revolution(BOR) Crank-Nicolson Douglas-Gunn(CNDG) finite-difference time-domain(FDTD) perfectly matched layer(PML) rotationally symmetric multi-scale problems

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A synthesis of the Cretaceous wildfire record related to atmospheric oxygen levels?

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Journal of Palaeogeography 2024年第1期13卷 149-164页

作者： da-Wei Lü wen-xu Du Zhi-Hui Zhang Yuan Gao Tian-Tian Wang Jin-Cheng xu Ao-Cong Zhang Cheng-Shan Wang Shandong Provincial Key Laboratory of Depositional Mineralization and Sedimentary Minerals College of Earth Sciences and EngineeringShandong University of Science and TechnologyQingdao 266590Shandong ProvinceChina School of Earth Sciences and Resources China University of GeosciencesBejing 100083China Institute of Earth Sciences China University of Geosciences(Bejing)Beijing 100083China

The Cretaceous was a significant greenhouse period in Earth's history with higher atmospheric CO_(2) levels and temperatures than today. Although evidence of combustion has been widely described from the Cretaceous deposits, our understanding of the spatiotemporal diversification pattern and process of the Cretaceous wildfires is still limited. In this study, we comprehensively synthesize a total of 271 published Cretaceous wildfire occurrences based on the by-products of burning, including fossil charcoal, pyrogenic inertinite(fossil charcoal in coal), and pyrogenic polycyclic aromatic hydrocarbons(PAHs). Spatially, the dataset shows a distinctive distribution of reported wildfire evidence characterized by high concentration in the middle latitudinal areas of the Northern Hemisphere(30°N-60°N) over the Cretaceous. Temporally, an overall increasing trend of the reported wildfire data from the Early Cretaceous to the Late Cretaceous is coincident with higher atmospheric O_(2) levels. However, the spatial and temporal patterns may result from many types of factors, such as taphonomy, preservation, and researcher biases, instead of a real picture of the Cretaceous wildfire evolution. To better understand the spatiotemporal diversification of the Cretaceous wildfire, more investigations on the record of wildfire occurrences during this period would be necessary in the future.

关键词： Wildfire Cretaceous Atmospheric oxygen Taphonomy Charcoal

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Study on a conical bearing for acceleration-sensitive equipment

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Earthquake Engineering and Engineering Vibration 2024年第1期23卷 103-128页

作者： Pang Hui xu wen dai Junwu Jiang Tao Key Laboratory of Earthquake Engineering and Engineering Vibration Institute of Engineering MechanicsChina Earthquake AdministrationHarbin 150080China Key Laboratory of Earthquake Disaster Mitigation Ministry of Emergency ManagementHarbin 150080China School of Civil Engineering and Transportation Beihua UniversityJilin 132013China

Seismic isolation effectively reduces seismic demands on building structures by isolating the superstructure from ground vibrations during earthquakes.However,isolation strategies give less attention to acceleration-sensitive systems or equipment.Meanwhile,as the isolation layer’s displacement grows,the stiffness and frequency of traditional rolling and sliding isolation bearings increases,potentially causing self-centering and resonance concerns.As a result,a new conical pendulum bearing has been selected for acceleration-sensitive equipment to increase self-centering capacity,and additional viscous dampers are incorporated to enhance system damping.Moreover,the theoretical formula for conical pendulum bearings is supplied to analyze the device’s dynamic parameters,and shake table experiments are used to determine the proposed device’s isolation efficiency under various conditions.According to the test results,the newly proposed devices have remarkable isolation performance in terms of minimizing both acceleration and displacement responses.Finally,a numerical model of the isolation system is provided for further research,and the accuracy is demonstrated by the aforementioned experiments.

关键词： seismic isolation acceleration-sensitive equipment the conical pendulum bearing shake table tests isolation performance,numerical model

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