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| 1 | Mechanical properties of hepatocellular carcinoma cells显示文摘AIM: To study the viscoelastic properties of humanhepatocytss and helatocellulsr carcinoma (HCC) cellsunder cytoslelstal perturbation, and to further to study theviscoelastic properties and the adhesive properties of mousehepatorna cells (HTC) in different cell cycls.METHODS: Micropipette aspiration technique was adopted tomeasure viscoelastic coefficients and adhesion force tocollagen coated surface ofthe cells. Three kinds ofcytoskeleton perturbing agents, colchiclnes (Col),cytochalssin D (CD) and vinblastine (VBL), were used totreat HCC cells and hepatocytes and the effects of thesetreatent on cell viscoelastic coefficients were investigated.The experimental results were analyzed with a thres-elsmentstandard linear solid. Further, the viscoelastic properties ofHTC cells and the adhesion force of different cycle HTC cellswere also investigated. The synchronous G1 and S phasecells were achieved through thymine-2-desoryriboside andcolchicines sequential blockage method and thymine-2-desoryriboside blockage method respectively.RESULTS: The elastic coefficients, but not viscouscoefficient of HCC cells (k1 = 103.6± 12.6N.m-2, k2 =42.5±10.4N. m-2, μ = 4.5 ± 1.9Pa. s), were significantly higherthan the corresponding value for hepatocytes (K1 = 87.5 ±12.1N.m-2, k2 =33.3± 10.3N.m-2, μ=5.9±3.0Pa. s, P<0.01). Upon treatment with CD, the viscoelastic coefficients ofboth hepotocytes and HCC cells decreased consistently,with magnitudes for the decrease in elastic coefficients ofHCC cells (k1: 68.7 N.m-2 to 81.7N.m-2, 66.3 % to 78.9 %;k2: 34.5 N.m-2 to37.1N.m-2, 81.2% to 87.3 %, P<0.001)larger than those for normal hepatocytes (k1: 42.6N. m-2 to49.8N.nt-2, 48.7% to56.9 %; k2: 17.2N.m-2 to 20.4N.m-2,51.7 % to 61.3 %, P< 0.001). There was a little decrease inthe vlscous coefficient of HCC cells (2.0 to 3.4Pa. s, 44.4 to75.6 %, P<0.001) than that for hepatocytes (3.0 to 3.gPa.s, 50.8to 66.1% P<0.001). Upon trastment with Col andVBL, the elastic coefficients of hepatocytes generallyincreased or tended to increase while those of HCC cellsdecreased. HTC cells with 72.1% ofG1 phase and 98. 9 % ofS phase were achieved and high K1, k2 value and low μvalue were the general characlteristics of HTC cells. G1phase cells had higher K1 value and lower tμ value than Sphase cells had, and G1 phase HTC cells had strongeradhesive forces [(275.9±232.8) x 10-10N] than S phase cells[(161.2± 120.4) x l0-10N, P<0.001).CONCLUSION: The difference in both the pattern and themagnitude of the effect of cytoskeletal perturbing agent onthe viscoelastic properties between HCC cells andhepatocytes may reflect differencss in the state of thecytusieleton structure and function and in the sensitivity toperturbing agent treatment between trinse two types of cells.Change in the viscoelastic properties of cancer cells mayaffect significantly tumor cell invasion and metastasis as wellas interactions between tumor cells and their micro-mechanical environments. | Gang Zhang,Department of Pathophysiology,The Third Military Medical University,Chongqing 400038,China Mian Long Zhe-Zhi Wu Wei-Qun Yu,College of Bioengineer,Chongqing university,Chongqing 400044,China | 2002 | World Journal of Gastroenterology2002，8，2： | 19 |
| 2 | Mechanomics: an emerging field between biology and biomechanics显示文摘在 vivo 各种各样的房间感觉机械刺激,它开始到机械力量的下游的发信号。当证据的身体在过去的十年在有限机械管理者的影响上被介绍时,机制 biomechanical 回答怎么全球性影响房间函数需要被探讨。复杂性和差异在 vivo,机械线索介绍不同模式砍有它的大小,持续时间,或频率的各种各样的参量的联合的流动,张力的段,或机械压缩。因此,理解被要求,从 mechanobiology 的观点,房间的机械特征是什么,机械性质为什么,并且怎么在不同房间类型之中是不同的力量是到下游地生物化学的信号的 transduced。同时,那些通常在 vivo 一起在孤立的机械刺激是的 vitro 联合了,建议是的不同因素能个别地实际上被抵销或与对方一起安排了。显然, omics 分析,系统生物学的地里的一个强大的工具,是有益的与 mechanobiology 结合然后印射它的染色体编码的机械地敏感的蛋白质和抄本完整集合。这块新出现地,也就是 mechanomics,使阐明可能在系统地变化的机械刺激下面的全球回答。这评论在 mechanomics 的相关的地里讨论当前的进展并且详细描述房间怎么察觉到外部力量并且激活生物回答。 | Jiawen Wang Dongyuan Lu Debin Mao Mian Long | 2014 | Protein & Cell2014，5，7： | 12 |
| 3 | Space experimental studies of microgravity fluid science in China显示文摘Microgravity fluid physics is an important part of microgravity sciences, which consists of simple fluids of many new systems, gas-liquid two-phase flow and heat transfer, and complex fluid mechanics. In addition to the importance of itself in sciences and applications, microgravity fluid physics closely relates to microgravity combustion, space biotechnology and space materials science, and promotes the developments of interdisciplinary fields. Many space microgravity experiments have been performed on board the recoverable satellites and space ships of China and pushed the rapid development of microgravity sciences in China. In the present paper, space experimental studies and the main results of the microgravity fluid science in China in the last 10 years or so are introduced briefly. | HU WenRui LONG Mian KANG Qi XIE JingChang HOU MeiYing ZHAO JianFu DUAN Li WANG ShuangFeng | 2009 | Chinese Science Bulletin2009，54，22： | 10 |
| 4 | Identification of the deposited layers in landslides reservoir and investigation of the sediment yields during the later sixteenth century on the Hill Loess Plateau,China显示文摘There are many sediment trapping reservoirs in the Hill Loess Plateau.The Huangtuwa small catchment is selected as a research field where samples were collected in a sediment deposit profile with a vertical length of 12.73 m.By the variation of fine particle content and pollen concentration,54 flood couples were identified.Taking the freeze-thawing disturbed texture as the sign of the latest flood couple in a year,it is ascertained that those 54 floods should happen in 31 years.Using pyramid volume calculation formula,the sediment yields of flood ranged between 716―30376 t·km-2.The average sediment yield was 7106 t·km-2.The annual sediment yields varied between 968―55579 t·(km2·a) -1,and the average value is 12629 t·(km2·a) -1.Compared with the modern annual sediment discharge of the Huaining River,the erosion rate in the Huangtuwa region 450 years ago was similar to the modern erosion rate.In the period from the 27th year to the 31st year,the average annual sediment yield increased sharply to 31309 t·(km2·a) -1.It implied that re-reclamation of the abandoned land in the catchment since the landslide disaster,where vegetation had rehabilitated already,caused very severe soil erosion in the catchment. | LONG Yi ZHANG XinBao LI Min LI Mian ZHANG YunQi | 2008 | Chinese Science Bulletin2008，53，24： | 9 |
| 5 | Effects of oriented substrates on cell morphology,the cell cycle,and the cytoskeleton in Ros 17/2.8 cells显示文摘Absence of gravity or microgravity influences the cellular functions of bone forming osteoblasts.The underlying mechanism,however,of cellular sensing and responding to the gravity vector is poorly understood.This work quantified the impact of vector-directional gravity on the biological responses of Ros 17/2.8 cells grown on upward-,downward-or edge-on-oriented substrates.Cell morphology and nuclear translocation,cell proliferation and the cell cycle,and cytoskeletal reorganization were found to vary significantly in the three orientations.All of the responses were duration-dependent.These results provide a new insight into understanding how osteoblasts respond to static vector-directional gravity. | LI Hong,CHEN Juan,ZHANG Yan,SUN ShuJin,TAO ZuLai & LONG Mian* Key Laboratory of Microgravity,Institute of Mechanics,Chinese Academy of Sciences,and National Microgravity Laboratory and Center for Biomechanics and Bioengineering,Institute of Mechanics,Chinese Academy of Sciences,Beijing 100190,China | 2010 | Science China(Life Sciences)2010，53，9： | 5 |
| 6 | Mechanokinetics of receptor-ligand interactions in cell adhesion显示文摘Receptor-ligand interactions in blood flow are crucial to initiate such biological processes as inflammatory cascade,platelet thrombosis,as well as tumor metastasis.To mediate cell adhesion,the interacting receptors and ligands must be anchored onto two apposing surfaces of two cells or a cell and a substratum,i.e.,two-dimensional(2D)binding,which is different from the binding of a soluble ligand in fluid phase to a receptor,i.e.,three-dimensional(3D) binding.While numerous works have been focused on3 D kinetics of receptor-ligand interactions in the immune system,2D kinetics and its regulations have been less understood,since no theoretical framework or experimental assays were established until 1993.Not only does the molecular structure dominate 2D binding kinetics,but the shear force in blood flow also regulates cell adhesion mediated by interacting receptors and ligands.Here,we provide an overview of current progress in 2D binding and regulations,mainly from our group.Relevant issues of theoretical frameworks,experimental measurements,kinetic rates and binding affinities,and force regulations are discussed. | Ning Li Shouqin Lü Yan Zhang Mian Long | 2015 | Acta Mechanica Sinica2015，31，2： | 5 |
| 7 | Flow dynamics analyses of pathophysiological liver lobules using porous media theory显示文摘Blood flow inside the liver plays a key role in hepatic functions, and abnormal hemodynamics are highly correlated with liver diseases. To date, the flow field in an elementary building block of the organ, the liver lobule,is difficult to determine experimentally in humans due to its complicated structure, with radially branched microvasculature and the technical difficulties that derive from its geometric constraints. Here we established a set of 3D computational models for a liver lobule using porous media theory and analyzed its flow dynamics in normal, fibrotic,and cirrhotic lobules. Our simulations indicated that those approximations of ordinary flow in portal tracts(PTs) and the central vein, and of porous media flow in the sinusoidal network, were reasonable only for normal or fibrotic lobules.Models modified with high resistance in PTs and collateral vessels inside sinusoids were able to describe the flow features in cirrhotic lobules. Pressures, average velocities, and volume flow rates were profiled and the predictions compared well with experimental data. This study furthered our understanding of the flow dynamics features of liver lobules and the differences among normal, fibrotic, and cirrhotic lobules. | Jinrong Hu Shouqin Lü Shiliang Feng Mian Long | 2017 | Acta Mechanica Sinica2017，33，4： | 4 |
| 8 | Adhesive properties of hepatoma cells to collagen Ⅳ coated surfaces显示文摘Objectives: To quantitatively study the adhesive pro-perties of hepatoma cells to collagen Ⅳ coated artifi-cial basement membrane and to investigate the rele-vance of cell adhesive forces to the concentration ofcollagen Ⅳ.Methods: Synchronous G1 and S phase cells were a-chieved using thymine-2-desoxyriboside and cochicinesequential blockage method and double thymine-2-desoxyriboside blockage method respectively. Theadhesive forces of hepatoma cells were investigatedby micropipette aspiration technique.Results: The adhesive forces of hepatoma cells to ar-tificial basement membrane were (107.78±65.44)×10-10N, (182.60±107.88)×10-10N, (298.91±144.13)×10-10N when the concentration of themembrane coated by 1, 2, 5μg/ml collagen Ⅳ re-spectively (P<0.001). The adhesive forces of G1and S phases hepatoma cells to artificial basementmembrane were (275.86±232.80)×10-10N and(161.16±120.40)×10-10N respectively when theconcentration of the membrane coated by 5μg/mlcollagen Ⅳ (P<0.001).Conclusions: The adhesive forces of hepatoma cells toartifical basement membrane in direct proportion tothe concentration of collagen Ⅳ suggests that the in-crease of basement membrane might be conducive tothe chemotactic motion and adhesiveness of tumorcells. G1 phase cells are more capable of adhering tobasement membrane than S phase cells. Hepatomacells, especially G1 phase cells, may survive in bloodcirculation, and sequest and adhere in microcircula-tion, and get through basement membrane for re-mote metastasis. | Ting Zhao Zhi-Qiang Ling Wei-Qun Yu Mian Long Shao-Xi Cai the Department of Surgery, Zhejiang Provincial Hospital, Hangzhou 310014, China Zhejiang Academy of Medical Sciences, Hangzhou 310013, China Bioengineering College, Chongqing University, Chongqing 400044, China | 2002 | Hepatobiliary & Pancreatic Diseases International2002，1，4： | 3 |
| 9 | Developing a microfluidic-based system to quantify cell capture efficiency显示文摘Micro-fabrication technology has substantial potential for identifying molecular markers expressed on the surfaces of tissue cells and viruses. It has been found in several conceptual prototypes that cells with such markers are able to be captured by their antibodies immobilized on microchannel substrates and unbound cells are flushed out by a driven flow. The feasibility and reliability of such a microflu- idic-based assay, however, remains to be further tested. In the current work, we developed a microflu- idic-based system consisting of a microfluidic chip, an image grabbing unit, data acquisition and analysis software, as well as a supporting base. Specific binding of CD59-expressed or BSA-coupled human red blood cells (RBCs) to anti-CD59 or anti-BSA antibody-immobilized chip surfaces was quan- tified by capture efficiency and by the fraction of bound cells. Impacts of respective flow rate, cell concentration, antibody concentration and site density were tested systematically. The measured data indicated that the assay was robust. The robustness was further confirmed by capture efficiencies measured from an independent ELISA-based cell binding assay. These results demonstrated that the system developed provided a new platform to effectively quantify cellular surface markers effectively, which promoted the potential applications in both biological studies and clinical diagnoses. | YANG Fan, GAO YuXin, ZHANG Yan, CHEN Juan & LONG Mian National Microgravity Laboratory and Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100080, China | 2009 | Science China(Life Sciences)2009，52，2： | 3 |
| 10 | Probe stiffness regulates receptor-ligand bond lifetime under force显示文摘Receptor-ligand bond dissociation under applied force is crucial to elucidate its biological functionality when the molecular bond is usually connected to a mechanical probe. While the impact of probe stiffness, k, on bond rupture force has recently attracted more and more attention, the mechanism of how it affects the bond lifetime, however, remains unclear. Here we quantified the dissociation lifetime of selectin-ligand bond using an optical trap assay with low stiffness ranging from 3.5×10-3 to 4.7×10-2 pN/nm. Our results indicated that bond lifetime yielded distinct distributions with different probe stiffness, implying the stochastic feature of bond dissociation. It was also found that the mean lifetime varied with probe stiffness and that the catch bond nature was visualized at k■3.0×10-2 pN/nm. This work furthered the understanding of the forced dissociation of selectin-ligand bond at varied probe stiffness, which is physiologically relevant to the tethered rolling of leukocytes under blood flow. | ZHANG Yan LüShouQin &LONG Mian | 2011 | Science China(Physics,Mechanics & Astronomy)2011，54，5： | 3 |
| 11 | Association between Coronary Atherosclerotic Plaque Composition and Cardiovascular Disease Risk显示文摘Objective The objective of this study is to determine whether coronary atherosclerotic plaque composition is associated with cardiovascular disease(CVD) risk in Chinese adults. Methods We performed a cross-sectional analysis in 549 subjects without previous diagnosis or clinical symptoms of CVD in a community cohort of middle-aged Chinese adults. The participants underwent coronary computed tomography(CT) angiography for the evaluation of the presence and composition of coronary plaques. CVD risk was evaluated by the Framingham risk score(FRS) and the 10-year atherosclerotic cardiovascular disease(ASCVD) risk score. Results Among the 549 participants, 267(48.6%) had no coronary plaques, 201(36.6%) had noncalcified coronary plaques, and 81(14.8%) had calcified or mixed coronary plaques. The measures of CVD risk including FRS and ASCVD risk score and the likelihood of having elevated FRS significantly increased across the groups of participants without coronary plaques, with noncalcified coronary plaques, and with calcified or mixed coronary plaques. However, only calcified or mixed coronary plaques were significantly associated with an elevated ASCVD risk score [odds ratio(OR) 2.41; 95% confidence interval(CI) 1.09-5.32] compared with no coronary plaques, whereas no significant association was found for noncalcified coronary plaques and elevated ASCVD risk score(OR 1.25; 95% CI 0.71-2.21) after multivariable adjustment. Conclusion Calcified or mixed coronary plaques might be more associated with an elevated likelihood of having CVD than noncalcified coronary plaques. | LI Lin WANG Long LIU Shan Shan ZHAO Zhi Yun LI Mian WANG Tian Ge XU Min LU Jie Li CHEN Yu Hong WANG Shuang Yuan DAI Meng HOU Ya Nan WU Xue Yan MA Li Na WANG Wei Qing XU Yu BI Yu Fang | 2019 | Biomedical and Environmental Sciences2019，32，2： | 3 |
| 12 | Spreading of human neutrophils on an ICAM-1-immobilized substrate under shear flow显示文摘Neutrophil (PMN) spreading on endothelium, mediated by the interactions between surface-bound β2 integrin and intercellular adhesion molecule-1 (ICAM-1) in the inflammatory cascade, is crucial for PMN post-adhesion and trans-migration in blood flow. The underlying mechanisms by which shear flow regulates PMN spreading dynamics are not well understood. Here, a parallel-plate flow chamber assay was applied to quantify the time course of PMN adhesion and spreading on an ICAM-1-immobilized substrate. Two types of shear flow, steady flows at shear stresses of 0.2, 0.5, and 1 dyne/cm2 and stepwise flows at 0, 1, and 10 dyne/cm2, were used to elucidate the impact of shear flow on cell adhesion and spreading. The number of adhered PMNs, the fraction of spreading PMNs and the projected area of spread PMNs were determined and were found to correlate with the distribution of surface-bound β2 integrin subunit (CD11a, CD11b, or CD18). The results indicate that PMN spreading on an ICAM-1 substrate is bi-directionally regulated under shear flow. CD11a, CD11b and CD18 subunits of β2 integrin contribute distinctly to PMN spreading on ICAM-1 substrates. This work provides new insights into understanding PMN spreading on the endothelium, mediated by β2 integrin and ICAM-1 under shear flow. | ZHAN DongYing ZHANG Yan LONG Mian | 2012 | Chinese Science Bulletin2012，57，7： | 2 |
| 13 | Global mapping of live cell mechanical features using PeakForce QNM AFM显示文摘Atomic force microscopy(AFM)has been widely used to acquire surface topography upon different scanning modes and to quantify mechanical properties of a cell using single-point ramp force mode.However,these traditional measurements need massive force curves originating from multiple points of a cell to exclude the potential errors resulted from limited and factitious selections of testing points,making the measurements time-consurming and highly localized.PeakForce Quantitative NanoMe-chanics(PF QNM)is a high-speed(faster by 3-4 order of magnitude)and global surface mechanical property mapping method with high spatial resolution,overcoming the drawbacks of traditional ramp mode especially used for a live cell with high heterogeneity.In this protocol,we elaborated how to run PF QNM measurements for live cells and relevant modification may be needed when extending this method to other cell-like soft materials. | Jinrong Hu Shenbao Chen Dandan Huang Yan Zhang Shouqin Lü Mian Long | 2020 | Biophysics Reports2020，6，1： | 2 |
| 14 | Kinetics of Receptor-Ligand Interactions in Immune Responses显示文摘在血流动的 Receptor-ligand 相互作用是关键的作为煽动性的串联,血小板血栓,以及肿瘤转移开始生物过程。为了调停,房间粘附,交往的受体和 ligands 必须被抛锚到二个房间或一个房间和一个基础的二 apposing 表面上,即,二维( 2D )绑定,与在到受体的液体阶段的可溶的 ligand 的绑定不同,三维( 3D )有约束力。当众多的工作在免疫系统集中于 receptor-ligand 相互作用的 3D 动力学时, 2D 动力学和它的规定少些被理解,自从没有理论框架和试验性的试金被建立了直到 1993。不仅分子的结构统治在血流动的力量也调整的 2D 绑定动力学,而是 shear 房间粘附由交往的受体和 ligands 调停了。这里,我们在 2D 绑定和规定提供了当前的进步的概述。理论框架,试验性的大小,运动的率和有约束力的亲密关系的相关问题,和力量规定,被讨论。 | Mian Long Shouqin Lue Ganyun Sun | 2006 | Cellular & Molecular Immunology2006，3，2： | 2 |
| 15 | Combined modeling of cell aggregation and adhesion mediated by receptor–ligand interactions under shear flow显示文摘Blood cell aggregation and adhesion to endothelial cells under shear flow are crucial to many biological processes such as thrombi formation, inflammatory cascade, and tumor metastasis, in which these cellular interactions are mainly mediated by the underlying receptor–ligand bindings. While theoretical modeling of aggregation dynamics and adhesion kinetics of interacting cells have been well studied separately, how to couple these two processes remains unclear. Here we develop a combined model that couples cellular aggregation dynamics and adhesion kinetics under shear flow. The impacts of shear rate(or shear stress)and molecular binding affinity were elucidated. This study provides a unified model where the action of a fluid flow drives cell aggregation and adhesion under the modulations of the mechanical shear flow and receptor–ligand interaction kinetics. It offers an insight into understanding the relevant biological processes and functions. | Yu Du Shuang Peng Yuhong Cui Shouqin Lü Yan Zhang Mian Long | 2015 | Theoretical & Applied Mechanics Letters2015，5，6： | 1 |
| 16 | Distinct Kinetics Features of LFA-1 and Mac-1 in Neutrophil Activation显示文摘LFA-1 and Mac-1, two β2integrin members constitutively expressed on neutrophils, mediate leukocyte recruitment cascade by binding to the same ligand of ICAM-1. The slow rolling and firm adhesion of leukocytes rely on LFA-1 while the cell crawling is dependent on Mac-1. We hypothesized that their distinct roles are likely attributed to the differences in the binding kinetics or in the diverse responses of outside-in and inside-out signaling. In this study, we compared the ICAM-1 binding features between soluble or membrane-expressed LFA-1 and Mac-1 with different affinity conformation using optical trap technique. Our data indicated that the affinity up-regulation from wide type(WT) to high affinity(HA) is off-rate dependent for LFA-1but on-rate dependent for Mac-1. The structural bases of this new finding were found to be consistent with our previous simulations. These results furthered our understanding in their function differences under shear flow. | LI Ning MAO De-bin GONG Yi-xin LV Shou-qin ZHANG Yan LONG Mian | 2015 | Chinese Journal of Biomedical Engineering(English Edition)2015，24，1： | 1 |
| 17 | Measuring binding kinetics of surface- bound molecules using the Surface plasmon resonance technique显示文摘 | Bao- Xia Li Juan Chen Mian Long | 2008 | Analytical Biochemistry2008，377，： | 1 |
| 18 | Comparison of the viscoelastic properties of normal hepatocytes and hepatocellular carcinoma cells under cytoskeletal perturbation显示文摘 | WU Zezhi ZHANG Gang LONG Mian | 2000 | Biorheology2000，37，4： | 1 |
| 19 | Flow field analyses of a porous membrane-separated,double-layered microfluidic chip for cell co-culture显示文摘Organs-on-chips composed of a porous membrane-separated,double-layered channels are used widely in elucidating the effects of cell co-culture and flow shear on biological functions.While the diversity of channel geometry and membrane permeability is applied,their quantitative correlation with flow features is still unclear.Immersed boundary methods(IBM)simulations and theoretical modelling were performed in this study.Numerical simulations showed that channel length,height and membrane permeability jointly regulated the flow features of flux,penetration velocity and wall shear stress(WSS).Increase of channel length,lower channel height or membrane permeability monotonically reduced the flow flux,velocity and WSS in upper channel before reaching a plateau.While the flow flux in lower channel monotonically increased with the increase of each factor,the WSS surprisingly exhibited a biphasic pattern with first increase and then decrease with increase of lower channel height.Moreover,the transition threshold of maximum WSS was sensitive to the channel length and membrane permeability.Theoretical modeling,integrating the transmembrane pressure difference and inlet flow flux with chip geometry and membrane permeability,was in good agreement with IBM simulations.These analyses provided theoretical bases for optimizing flow-specified chip design and evaluating flow microenvironments of in vivo tissue. | Shenbao Chen Jian Xue Jinrong Hu Qihan Ding Luwen Zhou Shiliang Feng Yuhong Cui Shouqin Lu Mian Long | 2020 | Acta Mechanica Sinica2020，36，3： | 1 |
| 20 | Kinetic Measurements of Cell Surface E-Selectin/Carbohydrate Ligand Interactions显示文摘 | Mian Long Hong Zhao Kuo-Sen Huang Cheng Zhu | 2001 | Annals of Biomedical Engineering2001，，11： | 1 |
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