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High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells

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World Journal of Stem Cells 2024年第2期16卷 176-190页

作者： Yu-Su Wang Wen-Hui Chu Jing-Jie zhai Wen-Ying Wang Zhong-Mei He Quan-Min zhao Chun-Yi Li Institute of Antler Science and Product Technology Changchun Sci-Tech UniversityChangchun 130000Jilin ProvinceChina College of Chinese Medicinal Materials Jilin Agricultural UniversityChangchun 130118Jilin ProvinceChina School of Life Science Taizhou UniversityTaizhou 318000Zhejiang ProvinceChina Department of Oral Implantology Hospital of StomatologyJilin UniversityChangchun 130000Jilin ProvinceChina

BACKGROUND Cartilage defects are some of the most common causes of *** lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral *** studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral *** To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral *** We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM *** sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the *** weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee *** The defects were successfully repaired by applying the *** highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem *** Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

关键词： Osteochondral defect repair Mesenchymal stem cells Extracellular matrix Decellularization Antler stem cells Reserve mesenchymal cells Xenogeneic

Rational protein engineering of thermostable heparinase I from Bacteroides thetaiotaomicron for highly efficient heparin degradation

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Food Science and Human Wellness 2024年

作者： Chuan Zhang Ruohan zhao Leilei Yu Qixiao zhai Jianxin zhao Hao Zhang Xuegang Luo Fengwei Tian Wei Chen State Key Laboratory of Food Science and Technology， Jiangnan University School of Food Science and Technology， Jiangnan University Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education & Tianjin Key Lab of Industrial Microbiology， College of Biotechnology， Tianjin University of Science and Technology National Engineering Research Center for Functional Food， Jiangnan University

Heparin， a glycosaminoglycan， is a stable source of carbon that supports the growth of microorganisms in the human intestine. It is also a commonly used anticoagulant drug in clinical practice， with significant therapeutic effects. Low molecular weight heparin （LMWH） is a highly active low molecular weight fragment obtained via enzymatic reaction or the chemical degradation of heparin. LMWH has been applied globally in the prevention and treatment of venous thromboembolism in thrombosis patients. Simultaneously， as a potential prebiotic， because of its low molecular weight， LMWH can be well degraded by the gut microbiota to maintain intestinal balance. Enzymatic heparin degradation has recently emerged as a viable disposal method for LMWH preparation; however， only very few benchmark enzymes have been thoroughly described and subjected to protein engineering to improve their properties over the past few years. The commercialization of enzymes will require the development of robustly engineered enzymes that meet the demands of industrial processes. Herein， we report a rational protein engineering strategy that includes molecular dynamic simulations of flexible amino acid mutations and disulfide bond screening. Several Bt-HepI mutants were obtained and screened for high thermal stability. We obtained the Bt-HepID204C/K208C/H189W/Q198Rvariant， which features a stabilized protein surface structure， with a 1.3-fold increase in kcat/Km， a 2.44-fold increase in thermal stability at 50℃， and a 1.8-fold decrease in the average molecular weight of LMWH produced at 40℃ compared with that seen with Bt-HepIWT. Our study establishes a strategy to engineer thermostable HepI to underpin its industrial applications.

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Prognostic significance of Borrmann type combined with vessel invasion status in advanced gastric cancer

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World Journal of Gastrointestinal Oncology 2020年第9期12卷 992-1004页

作者： zhao zhai Zi-Yu Zhu Yu Zhang Xin Yin Bang-Ling Han Jia-Liang Gao Sheng-Han Lou Tian-Yi Fang Yi-Min Wang Chun-Feng Li Xue-Feng Yu Yan Ma Ying-Wei Xue Department of Gastroenterological Surgery Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina

BACKGROUND Borrmann classification(types I-IV)for the detection of advanced gastric cancer has been accepted worldwide,and lymphatic and/or blood vessel invasion(LBVI)status is related to the poor prognosis after gastric *** To evaluate the significance of Borrmann type combined with LBVI status in predicting the prognosis of advanced gastric *** We retrospectively studied the clinicopathological characteristics and long-term survival data of 2604 patients who were diagnosed with advanced gastric adenocarcinoma at Harbin Medical University Cancer Hospital from January 2009 to December *** variables were evaluated by the Pearson’sχ^2 test,the Kaplan-Meier method was used to identify differences in cumulative survival rates,and the Cox proportional hazards model was used for multivariate prognostic *** A total of 2604 patients were included in this *** presence of LVBI[LBVI(+)]and Borrmann type(P=0.001),tumor location(P<0.001),tumor size(P<0.001),histological type(P<0.001),tumor invasion depth(P<0.001),number of metastatic lymph nodes(P<0.001),and surgical method(P<0.001)were significantly correlated with *** analyzing the combination of the Borrmann classification and LBVI status,we found that patients with Borrmann type Ⅲ disease and LBVI(+)had a similar 5-year survival rate to those with Borrmann IV+LBVI(-)(16.4%vs 13.1%,P=0.065)and those with Borrmann IV+LBVI(+)(16.4%vs 11.2%,P=0.112).Subgroup analysis showed that the above results were true for any pT stage and any tumor *** Cox regression analysis showed that Borrmann classification(P=0.023),vascular infiltration(P<0.001),tumor size(P=0.012),pT stage(P<0.001),pN stage(P<0.001),and extent of radical surgery(P<0.001)were independent prognostic factors for *** Since patients with Borrmann Ⅲ disease and LBVI(+)have the same poor prognosis as those with Borrmann IV disease,more attention should be paid to patients with Borrm

关键词： Advanced gastric cancer Borrmann type Vascular invasion Long-term survival

A Prediction Model for Detecting Dysthyroid Optic Neuropathy Based on Clinical Factors and Imaging Markers of the Optic Nerve and Cerebrospinal Fluid in the Optic Nerve Sheath

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Current Medical Science 2024年第4期44卷 827-832页

作者： Hong-yu WU Ban LUO Gang YUAN Qiu-xia WANG Ping LIU Ya-li zhao Lin-han zhai Wen-zhi LV Jing ZHANG Lang CHEN Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Ophthalmology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Endocrinology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Medical Imaging Guangdong Second Provincial General HospitalGuangzhou510317China Department of Radiology Sir Run Run Shaw Hospital Affiliated with the School of Medicine of Zhejiang UniversityHangzhou310000China Department of Artificial Intelligence Julei Technology CompanyWuhan430030China

Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve *** This retrospective study included patients with thyroid-associated ophthalmopathy(TAO)without DON and patients with TAO accompanied by DON at our *** imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and,together with clinical factors,were screened by Least absolute shrinkage and selection ***,we constructed a prediction model using multivariate logistic *** accuracy of the model was verified using receiver operating characteristic curve *** In total,80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our *** variables(optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath)were found to be independent predictive factors and were included in the prediction *** the development cohort,the mean area under the curve(AUC)was 0.994,with a sensitivity of 0.944,specificity of 0.967,and accuracy of ***,in the validation cohort,the AUC was 0.960,the sensitivity was 0.889,the specificity was 0.893,and the accuracy was *** A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath,serving as a noninvasive potential tool to predict DON.

关键词： dysthyroid optic neuropathy magnetic resonance imaging water-fat sequence optic nerve optic nerve subarachnoid space

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

Development of LAG-3/FGL1 blocking peptide and combination with radiotherapy for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1150-1165页

作者： Yuzhen Qian Yixuan Sun Peishang Shi Xiuman Zhou Qiongqiong Zhang Qingyu Dong Shengzhe Jin Lu Qiu Xiaoshuang Niu Xiaowen Zhou Wenshan zhao Yahong Wu Wenjie zhai Yanfeng Gao School of Life Sciences Zhengzhou UniversityZhengzhou 450001China School of Pharmaceutical Sciences(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107China International Joint Laboratory for Protein and Peptide Drugs of Henan Province Zhengzhou UniversityZhengzhou 450001China

Aside from antibodies,peptides show great potential as immune checkpoint inhibitors(ICIs)due to several advantages,such as better tumor penetration and lower ***-activation gene 3(LAG-3)is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1(FGL1).Here,we found that LAG-3 expression was higher than programmed cell death protein 1(PD-1)in multiple human cancers by TCGA databases,and successfully identified a LAG-3 binding peptide LFP-6 by phage display bio-panning,which specifically blocks the interaction of LAG-3/FGL1 but not LAG-3/***,D-amino acids were introduced to substitute the N-and C-terminus of LFP-6 to obtain the proteolysis-resistant peptide LFP-D1,which restores T cell function in vitro and inhibits tumor growth in ***,a bispecific peptide LFOP targeting both PD-1/PD-L1 and LAG-3/FGL1 was designed by conjugating LFP-D1 with PD-1/PD-L1blocking peptide OPBP-1(8-12),which activates T cell with enhanced proliferation and IFN-γ *** importantly,LFOP combined with radiotherapy significantly improve the T cell infiltration in tumor and elevate systemic antitumor immune *** conclusion,we developed a novel peptide blocking LAG-3/FGL1 which can restore T cell function,and the bispecific peptide synergizes with radiotherapy to further enhance the antitumor immune response.

关键词： LAG-3 FGL1 PD-1 PD-L1 Peptide Immune checkpoint Radiotherapy Cancer immunotherapy

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Xenus交流驱动器的调试及应用

火力与指挥控制 2014年第S1期39卷 189-192页

作者：翟昭斌国营第七八五厂太原030024

随着交流电机在自动控制系统中的广泛应用,与之相关的交流驱动器种类繁多,适用于不同的控制领域。Copley公司生产的交流驱动器是一款功能齐全,使用方便,调试简单,易于控制,适用范围广泛的产品。主要介绍Xenus驱动器的特点、功能,以及在... 详细信息

随着交流电机在自动控制系统中的广泛应用,与之相关的交流驱动器种类繁多,适用于不同的控制领域。Copley公司生产的交流驱动器是一款功能齐全,使用方便,调试简单,易于控制,适用范围广泛的产品。主要介绍Xenus驱动器的特点、功能,以及在某随动系统中的具体应用。

关键词：交流驱动器交流电机伺服系统速度环位置环

Changing trends of clinicopathologic features and survival duration after surgery for gastric cancer in Northeast China

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World Journal of Gastrointestinal Oncology 2020年第10期12卷 1119-1132页

作者： zhao zhai Zi-Yu Zhu Xi-Liang Cong Bang-Ling Han Jia-Liang Gao Xin Yin Yu Zhang Sheng-Han Lou Tian-Yi Fang Yi-Min Wang Chun-Feng Li Xue-Feng Yu Yan Ma Ying-Wei Xue Department of Gastroenterological Surgery Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina

BACKGROUND Through analyzing the data from a single institution in Northeast China,this study revealed the possible clinicopathologic characteristics that influence the prognosis of patients with gastric cancer(GC).AIM To evaluate the changing trends of clinicopathologic features and survival duration after surgery in patients with GC in Northeast China,which is a highprevalence area of *** The study analyzed the difference in clinicopathologic features and survival duration after surgery of 5887 patients who were histologically diagnosed with GC at the Harbin Medical University Cancer *** study mainly analyzed the data in three periods,2000 to 2004(Phase 1),2005 to 2009(Phase 2),and 2010 to 2014(Phase 3).RESULTS Over time,the postoperative survival rate significantly increased from 2000 to *** the past 15 years,compared with Phases 1 and 2,the tumor size was smaller in Phase 3(P<0.001),but the proportion of high-medium differentiated tumors increased(P<0.001).The proportion of early GC gradually increased from 3.9%to 14.4%(P<0.001).A surprising improvement was observed in the mean number of retrieved lymph nodes,ranging from 11.4 to 27.5(P<0.001).The overall 5-year survival rate increased from 24%in Phase 1 to 43.8%in Phase *** multivariate analysis,it was found that age,tumor size,histologic type,tumor-node-metastasis stage,depth of invasion,lymph node metastasis,surgical approach,local infiltration,radical extent,number of retrieved lymph nodes,and age group were independent risk factors that influenced the prognosis of patients with *** The clinical features of GC in Northeast China changed during the observation *** increasing detection of early GC and more standardized surgical treatment effectively prolonged lifetimes.

关键词： Gastric cancer Clinicopathologic features Survival Time trends Epidemiology Gastrectomy

Anatomic study of the Vestibular Apparatus by using FSE 3D H

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Anatomic study of the Vestibular Apparatus by using FSE 3D H