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Inhibition of LY294002 in retinal neovascularization via down-regulation the PI3K/AKT-VEGF pathway in vivo and in vitro

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International Journal of Ophthalmology(English edition) 2018年第8期11卷 1284-1289页

作者： Yu Di xiao-long chen Department of Ophthalmology Shengjing Affiliated HospitalChina Medical University

AIM： To investigate the effects of the phosphatidylinositol 3-kinase（PI3 K） inhibitor LY294002 on retinal neovascularization（RNV） in the oxygen-induced retinopathy（OIR） mouse model and human umbilical vein endothelial cells（HUVECs）.METHODS： C57 BL/6 J mice were randomly divided into normoxia-control, OIR-control and LY294002 treatment groups. LY294002 or phosphate-buffered solution was intraperitoneally injected daily into mouse pups from P6 to P9 in LY294002 treatment group or OIR-control group. Morphological and pathological changes in RNV, as well as expression levels of PI3 K, serine-threonine kinase（AKT） and vascular endothelial growth factor（VEGF） were observed. HUVECs treating with LY294002 were exposed to hypoxia; the expression of PI3 K, AKT and VEGF were examined by Western blot and RT-PCR ***： Compared with the OIR-control group, LY294002 significantly inhibit RNV. Adenosine diphosphatase（ADPase） staining and hematoxylin and eosin staining indicated that the clock hour scores of neovascularization and the nuclei of pre-retinal neovascular cells in the LY294002 treatment group were clearly less than those in the OIR-control group（1.41±0.52 vs 6.20±1.21; 10.50±1.58 vs 22.25±1.82, both P〈0.05）. Intravitreal injection of LY294002（in the LY294002 treatment group） markedly decreased PI3 K/AKT-VEGF expression compared with the OIR-control group by immunohistochemistry, Western blotting and RT-PCR（all P〈0.05）. In HUVECs treated with hypoxia, expression of PI3 K, AKT and VEGF were downregulated in the hypoxia-LY294002 group（all P〈0.05）.CONCLUSION： The PI3 K inhibitor LY294002 can inhibit RNV by downregulating PI3 K, AKT, and VEGF expression in vivo and in vitro. LY294002 may provide an effective method for preventing retinopathy of prematurity（ROP）.

关键词： vascular endothelial growth factor phospha-tidylinositol 3-kinase LY294002 retinopathy of prematurity retinal neovascularization

Efficacy of intravitreal captopril on oxygen-induced retinopathy in mice

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International Journal of Ophthalmology(English edition) 2011年第4期4卷 361-364页

作者： Yu Di, xiao-long chen Department of Ophthalmology Shengjing Hospital of China Medical University Shenyang 110004 Liaoning Province China Graduate School of China Medical University Shenyang 110001 Liaoning Province China

AIM: To study the inhibitory effect of intravitreal captopril on oxygen-induced retinopathy (OIR) in mice. METHODS: Eighty postnatal day (P)7 C57BL/63 mice were randomly divided into treated group and control group with forty mice in each group. The mice were exposed to 75% 2% oxygen for 5 days (P7-P11) and then returned to room air for 5 days (P12-P17) to induce retinal neovascularization (RNV). Beginning on P12, the mice in treated group received daily intravitreal injections of captopril(3.0mL/kg), while those in control group received daily intravitreal injections of phosphate-buffered saline (PBS) (3.0mL/kg) through P17. After anesthetized at P17, one eye was chosen randomly as experimental eye and were enucleated. RNV was examined by Adenosine diphosphate-ase (ADPase) stained retina flat-mounts and was quantitated histologically by counting the neovascular endothelial cell nuclei anterior to inner limiting membrane (ILM). The expressions of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) were measured by immunohistochemical method. RESULTS: Comparing with control group, more regular distributions, better branch and reduced density of RNV were observed in eyes of treated group. The number of neovascular cell nuclei was less in treated group than that in control group ( t =6.135, P <0.01). Stain of MMP-2 and VEGF was weaker in treated group than that in control group. CONCLUSION: The results indicate that captopril can significantly inhibit RNV in OIR mice.

关键词： retinal neovascularization oxygen-induced retinopathy captopril intravitreal injection

Effects of LY294002 on the function of retinal endothelial cell in vitro

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International Journal of Ophthalmology(English edition) 2018年第9期11卷 1447-1450页

作者： Yu Di xiao-long chen Department of Ophthalmology Shengjing Hospital of China Medical University

AIM： To study the effects of LY294002 [phosphatidylinositol 3-kinase（PI3K） inhibitor] on the function and mechanisms of retinal endothelial cells（RECs） in ***： RECs were randomly divided into control group and LY294002 treatment group. RECs in the control group were placed the incubator for hypoxic exposure in vitro. RECs in the LY294002 treatment group were pretreated with LY294002（40 μmol/L） under hypoxic condition. The expression of matrix metalloproteinase（MMP）-2, MMP-9, vascular endothelial growth factor（VEGF）, and apoptosis and proliferation of RECs were evaluated with Western blot, real-time reverse transcription-polymerase chain reaction（RT-PCR）, and flow cytometric analysis, ***： Compared with the control group, treating the RECs with LY294002 was able to remarkably inhibit cell proliferation rates（t_（1d）=2.13, t_（2d）=2.65, t_（3d）=2.36, t_（4d）=2.06, all P〈0.05）. Flow cytometric analysis indicated that a moderate increase in apoptosis in the LY294002 treatment group compared to the control group（t=2.51, P〈0.05）. The expression of MMP-2, MMP-9 and VEGF were downregulated in the LY294002 treatment group by Western blot and real-time RT-PCR（all P〈0.05）.CONCLUSION： LY294002 regulates the function of RECs by reducing the expression of MMP-2, MMP-9, and VEGF in vitro. LY294002 may provide an effective method for preventing pathological angiogenesis.

关键词： LY294002 phosphatidylinositol 3-kinase retinal endothelial cell angiogenesis

Collisional dynamics of symmetric two-dimensional quantum droplets

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Frontiers of physics 2022年第6期17卷 203-209页

作者： Yanming Hu Yifan Fei xiao-long chen Yunbo Zhang Institute of Theoretical Physics and State Key Laboratory of Quantum Optics and Quantum Optics Devices Shanxi UniversityTaiyuan 030006China Department of Physics and Key Laboratory of Optical Field Manipulation of Zhejiang Province Zhejiang Sci-Tech UniversityHangzhou 310018China

The collisional dynamics of two symmetric droplets with equal intraspecies scattering lengths and particle number density for each component is studied by solving the corresponding extended Gross–Pitaevskii equation in two dimensions by including a logarithmic correction term in the usual contact *** find the merging droplet after collision experiences a quadrupole oscillation in its shape and the oscillation period is found to be independent of the incidental momentum for small *** increasing collision momentum the colliding droplets may separate into two,or even more,and finally into small pieces of *** these dynamical phases we manage to present boundaries determined by the remnant particle number in the central area and the damped oscillation of the quadrupole mode.A stability peak for the existence of droplets emerges at the critical particle number Nc≃48 for the quasi-Gaussian and flat-top shapes of the droplets.

关键词： ultracold atoms quantum droplets collisions

Non-extensive statistical distributions of charmed meson production in Pb-Pb and pp(p)collisions

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Nuclear Science and Techniques 2021年第10期32卷 79-87页

作者： Yuan Su Yong-Jie Sun Yi-Fei Zhang xiao-long chen State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026China Department of Modern Physics University of Science and Technology of ChinaHefei 230026China

The mid-rapidity transverse momentum spectra of charmed mesons in Pb–Pb and pp(p)collisions are analyzed using the Tsallis–Pareto distribution derived from non-extensive *** provide uniform descriptions of both small and large systems over a wide range of collision energies and hadron transverse *** establishing the relationship between the event multiplicity and Tsallis parameters,we observe that there is a signifi-cant linear relationship between the thermal temperature and Tsallis q parameter in Pb–Pb collisions at √sNN=2.76 TeV and 5.02 ***,the slope of the T–(q-1)parameter plot is positively correlated with the hadron *** addition,charmed mesons have a higher thermal temperature than light hadrons at the same q-1,indicat-ing that the charm flavor requires a higher temperature to reach the same degree of non-extensivity as light flavors in heavy-ion *** same fit is applied to the trans-verse momentum spectra of charmed mesons in pp(p)collisions over a large energy range using the Tsallis–Pareto *** is found that the thermal temperature increases with system energy,whereas the q parameter becomes saturated at the pp(p)limit,q-1=0.142±*** addition,the results of most peripheral Pb–Pb collisions are found to approach the pp(p)limit,which suggests that more peripheral heavy-ion collisions are less affected by the medium and more similar to pp(p)collisions.

关键词： Charmed meson Non-extensive statistics Tsallis-Pareto distribution QGP Heavy-ion collision

Quercetin protects against diabetic retinopathy in rats by inducing heme oxygenase-1 expression

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Neural Regeneration Research 2021年第7期16卷 1344-1350页

作者： Guang-Rui Chai Shu Liu Hong-Wei Yang xiao-long chen Department of Ophthalmology Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Department of Geratology The First Affiliated Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Quercetin is a widely-occurring flavonoid that protects against cancer, and improves memory and cardiovascular ***, whether quercetin exhibits therapeutic effects in diabetic retinopathy remains *** this study, we established a rat model of streptozocininduced diabetic ***-two hours later, the rats were intraperitoneally administered 150 mg/kg quercetin for 16 successive *** markedly increased the thickness of the retinal cell layer, increased the number of ganglion cells, and decreased the overexpression of the pro-inflammatory factors interleukin-1β, interleukin-18, interleukin-6 and tumor necrosis factor-α in the retinal tissue as well as the overexpression of high mobility group box-1 and the overactivation of the NLRP3 ***, quercetin inhibited the overexpression of TLR4 and NF-κBp65, reduced the expression of the pro-angiogenic vascular endothelial growth factor and soluble intercellular adhesion molecule-1, and upregulated the neurotrophins brain-derived neurotrophic factor and nerve growth *** injection of the heme oxygenase-1 inhibitor zinc protoporphyrin blocked the protective effect of *** findings suggest that quercetin exerts therapeutic effects in diabetic retinopathy possibly by inducing heme oxygenase-1 *** study was approved by the Animal Ethics Committee of China Medical University, China(approval No.2016 PS229K) on April 8, 2016.

关键词： angiogenesis diabetic retinopathy flavonoid heme oxygenase-1 inflammation neurotrophin quercetin repair

Matrix metalloproteinase-9 and vascular endothelial growth factor expression change in experimental retinal neovascularization

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International Journal of Ophthalmology(English edition) 2016年第6期9卷 804-808页

作者： Yu Di Qing-Zhu Nie xiao-long chen Department of Ophthalmology Shengjing Hospital of China Medical University

AIM： To investigate the signal transduction mechanism of matrix metalloproteinase-9 （MMP-9） mediatedvascular endothelial growth factor （VEGF） expression and retinal neovascularization （RNV） in oxygen-induced retinopathy （OIR） model. METHODS： C57BL/6J mice were divided into four groups： control group, OIR group, OIR control group （phosphatebuffered saline by intravitreal injection） and treated group [tissue inhibitor of matrix metalloproteinase-1 （TIMP-1） by intravitreal injection]. OIR model was established in C57BIJ6J mice exposed to 75% ＋2% oxygen for 5d. mRNA level and protein expression of MMP-9, TIMP-1 and VEGF were measured by real-time polymerase chain reaction and Western blotting, and located by immunohistochemistry. RESULTS： Levels of MMP-9 and VEGF in retina were significantly increased in animals with OIR and OIR control group. Levels of TIMP -1 in retina was significantly reduced in animals with OIR and OIR control group. Furthermore, a significant correlation was found between MMP-9 and VEGF. Intravitreal injection of TIMP- 1 significantly reduced MMP-9 and VEGF expression of the OIR mouse model （all P〈0.05）. CONCLUSION： These results demonstrate that MMP- 9-mediated up-regulation of VEGF promotes RNV in retinopathy of prematurity （ROP）. TIMP-1 may be a potential target for the prevention and treatment of ROP.

关键词： retinal neovascularization matrixmetalloproteinase-9 vascular endothelial growth factor oxygen-induced retinopathy

Fabrication of micro pin fins on inclined V-shaped microchannel walls via laser micromilling

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Advances in Manufacturing 2022年第2期10卷 220-234页

作者： Da-Xiang Deng Jian Zheng xiao-long chen Guang Pi Yong-Heng Liu School of Mechanical Engineering and Automation Harbin Institute of TechnologyShenzhenShenzhen 518055GuangdongPeople's Republic of China Department of Mechanical and Electrical Engineering Xiamen UniversityXiamen 361005FujianPeople's Republic of China

A laser-micromilling process was developed for fabricating micro pin fins on inclined V-shaped microchannel walls for enhanced microchannel heat sinks.A pulsed nanosecond fiber laser was *** feasibility and mechanism of the formation of micro pin fins on inclined microchannel walls were investigated for a wide range of processing *** effects of the laser output power,scanning speed,and line spacing on the surface morphologies and geometric sizes of the micro-pin fins were comprehensively examined,together with the material removal *** pin fins with acute cone tips were readily formed on the V-shaped microchannel walls via the piling of recast layers and the downflow of re-solidified materials in the laser-ablation *** pin-fin height exhibited an increasing trend when the scanning speed increased from 100mm/s to 300 mm/s,and it decreased continuously when the line spacing increased from 5μm to 20μ*** optimal processing parameters for preparing micro pin fins on V-shaped microchannels were found to be a laser output power of 21 W,scanning speed of 100-300 mm/s,and line spacing of 2-5μ***,the V-shaped microchannels with micro pin fins induced a 7%-538%boiling heat-transfer enhancement over their counterpart without micro pin fins.

关键词： Laser micromilling Micro pin fins:Microchannels Inclined walls Laser ablation

Neoadjuvant plus adjuvant chemotherapy benefits overall survival of locally advanced gastric cancer

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World Journal of Gastroenterology 2011年第40期17卷 4542-4544页

作者： Xin-Zu chen Kun Yang Jie Liu xiao-long chen Jian-Kun Hu Department of Gastrointestinal Surgery West China Hospital Sichuan University Chengdu 610041 Sichuan Province China Faculty of Medicine West China Medical School Sichuan University Chengdu 610041 Sichuan Province China

Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally advanced gastric cancer (AGC) in the current multidisciplinary treatment model. EORTC trial 40954 has recently reported that NAC plus surgery without postoperative adjuvant chemotherapy could not benefit the locally AGC patients in their overall survival. We performed a meta-analysis of 10 studies including 1518 gastric cancer patients. Stratified subgroups were NAC plus surgery and NAC plus both surgery and adjuvant chemotherapy (AC), while control was surgery alone. The results showed that NAC plus surgery did not benefit the patients with locally AGC in their overall survival [odds ratio (OR) = 1.20, 95% CI 0.80-1.80, P = 0.37] and the number needed to treat (NNT) was 74. However, the NAC plus both surgery and AC had a slight overall survival benefit (OR = 1.33, 95% CI 1.03-1.71, P = 0.03) and NNT was 14, which is superior to the NAC plus surgery. Therefore, we recommend that combined NAC and AC should be used to improve the overall survival of the locally AGC patients.

关键词： Gastric cancer Adjuvant chemotherapy Neoadjuvant chemotherapy Surgery Survival