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Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1018-1027页

作者： yu-Sheng Zhu Si-Rui Zhou Hui-Hui Zhang tong Wang Xiao-Dong Chen Faculty of Life Sciences and Medicine Northwest UniversityXi’an 710069Shaanxi ProvinceChina First Affiliated Hospital of Northwest University Northwest UniversityXi’an 710069Shaanxi ProvinceChina Department of Ophthalmology Xi’an No.1 HospitalXi’an 710002Shaanxi ProvinceChina Shaanxi Institute of Ophthalmology Shaanxi Provincial Key Lab of OphthalmologyClinical Research Center for Ophthalmology Diseases of Shaanxi ProvinceXi’an 710002Shaanxi ProvinceChina

AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).

关键词： erlotinib epidermal growth factor receptor protein kinase B epithelial-mesenchymal transition retinal pigment epithelium cell

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The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

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Neural Regeneration Research 2024年第5期19卷 1084-1091页

作者： Yijing Zhao tong Li Zige Jiang Chengcheng Gai Shuwen yu Danqing Xin Tingting Li Dexiang Liu Zhen Wang Department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of Neurosurgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina Department of Medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao UniversityJinanShandong ProvinceChina

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

关键词： chemokine(C-X-C motif)ligand 11 cystathionineβsynthase H2S hypoxic ischemic brain injury inflammation L-cysteine lipopolysaccharide microglia miR-9-5p neuroprotection

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Values of macular ganglion cell-inner plexiform layer and 10-2 visual field measurements in detecting and evaluating glaucoma

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 852-860页

作者： Hai-Jian Hu Ping Li Bin tong yu-Lian Pang Hong-Dou Luo Fei-Fei Wang Chan Xiong yu-Lin yu Hai He Xu Zhang Affiliated Eye Hospital of Nanchang University Jiangxi Research Institute of Ophthalmology and Visual ScienceJiangxi Clinical Research Center for Ophthalmic DiseaseJiangxi Branch of National Clinical Research Center for Ocular DiseasesNanchang 330006Jiangxi ProvinceChina Wuhan Children’s Hospital(Wuhan Maternal and Child Healthcare Hospital) Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430015Hubei ProvinceChina

AIM:To assess the performance of macular ganglion cell-inner plexiform layer thickness(mGCIPLT)and 10-2 visual field(VF)parameters in detecting early glaucoma and evaluating the severity of advanced glaucoma.METHODS:Totally 127 eyes from 89 participants(36 eyes of 19 healthy participants,45 eyes of 31 early glaucoma patients and 46 eyes of 39 advanced glaucoma patients)were included.The relationships between the optical coherence tomography(OCT)-derived parameters and VF sensitivity were determined.Patients with early glaucoma were divided into eyes with or without central 10°of the VF damages(CVFDs),and the diagnostic performances of OCT-derived parameters were assessed.RESULTS:In early glaucoma,the mGCIPLT was significantly correlated with 10-2 VF pattern standard deviation(PSD;with average mGCIPLT:β=-0.046,95%CI,-0.067 to-0.024,P<0.001).In advanced glaucoma,the mGCIPLT was related to the 24-2 VF mean deviation(MD;with average mGCIPLT:β=0.397,95%CI,0.199 to 0.595,P<0.001),10-2 VF MD(with average mGCIPLT:β=0.762,95%CI,0.485 to 1.038,P<0.001)and 24-2 VF PSD(with average mGCIPLT:β=0.244,95%CI,0.124 to 0.364,P<0.001).Except for the minimum and superotemporal mGCIPLT,the decrease of mGCIPLT in early glaucomatous eyes with CVFDs was more severe than that of early glaucomatous eyes without CVFDs.The area under the curve(AUC)of the average mGCIPLT(AUC=0.949,95%CI,0.868 to 0.982)was greater than that of the average circumpapillary retinal nerve fiber layer thickness(cpRNFLT;AUC=0.827,95%CI,0.674 to 0.918)and rim area(AUC=0.799,95%CI,0.610 to 0.907)in early glaucomatous eyes with CVFDs versus normal eyes.CONCLUSION:The 10-2 VF and mGCIPLT parameters are complementary to 24-2 VF,cpRNFLT and ONH parameters,especially in detecting early glaucoma with CVFDs and evaluating the severity of advanced glaucoma in group level.

关键词： 10-2 visual field ganglion cell-inner plexiform layer retinal nerve fiber layer thickness glaucoma

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Generation of mitochondrial replacement monkeys by female pronucleus transfer

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Zoological Research 2024年第2期45卷 292-298页

作者： Chun-Yang Li Xing-Chen Liu yu-Zhuo Li Yan Wang Yan-Hong Nie yu-Ting Xu Xiao-tong Zhang Yong Lu Qiang Sun Institute of Neuroscience Center for Excellence in Brain Science and Intelligence TechnologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai 200031China Key Laboratory of Genetic Evolution and Animal Models Chinese Academy of SciencesKunming 650201China University of Chinese Academy of Sciences Beijing 100049China

Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe disorders.Mitochondrial replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA diseases.While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously reported.In this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear transfer.These individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during development.The successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

关键词： Non-human primates Mitochondrial replacement Female pronuclear transfer

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Protein C deficiency with venous and arterial thromboembolic events

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World Journal of Clinical Cases 2024年第12期12卷 2000-2003页

作者： Nan Zhang Dong-Kun Sun Xu Tian Xin-yu Zheng tong Liu Department of Cardiology Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular DiseaseTianjin Institute of CardiologyThe Second Hospital of Tianjin Medical UniversityTianjin 300211China

Protein C(PC)is a key component of the vitamin K-dependent coagulation pathway.It exerts anticoagulant effects by inactivating factors V and VIII.Acquired or inherited PC deficiency results in a prothrombotic state,with presentations varying from asymptomatic to venous thromboembolism.However,there has been an increasing number of reports linking PC deficiency to arterial thromboembolic events,such as myocardial infarction and ischemic stroke.This editorial focuses on the association between PC deficiency and thromboembolism,which may provide some insights for treatment strategy and scientific research.

关键词： Protein C deficiency Venous thromboembolism Myocardial infarction Editorial Arterial thromboembolism

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Network Pharmacology and Molecular Docking Analysis of the Mechanisms of Combined Radix Bupleuri(Chai-Hu) and Radix Paeoniae Alba(Bai-Shao) Treatment in the Prevention and Treatment of Alzheimer's Disease

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 254-262页

作者： Zhao-Han Huang yuan Fang Qi yu tong Wang College of Traditional Chinese Medicine Beijing University of Chinese Medicine Shanghai Center for Women and Children's Health

Objective: Radix Bupleuri and Radix Paeoniae Alba are referred to as Chai-Hu and Bai-Shao, respectively, in Chinese. We used molecular docking and network pharmacological approaches to explore the active components of this Chinese herb combination which is commonly used for treating Alzheimer's disease(AD), the Chai-Hu and Bai-Shao pair(CBP). Materials and Methods: The active compounds and action targets of Chai-Hu and Bai-Shao were identified in the Traditional Chinese Medicine Systems Pharmacology database, and the Therapeutic Target Database, Drug Bank, Gen Cards, Dis Ge NET, and Online Mendelian Inheritance in Man databases were used to identify therapeutic targets in patients with AD. To identify a common target of CBP in the treatment of AD, we used the Metascape tool to perform Gene Ontology function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. In addition, CBP-AD protein–protein interaction(PPI) and herb-component-target networks were created using Cytoscape 3.8.2. Molecular docking was verified using Auto Dock tools. Results: We identified 20 active compounds of CBP, 202 active targets, 1,323 disease targets, and 117 active compound disease intersection targets; the PPI network showed that the top eight key targets were AKT1, interleukin(IL) 6, JUN, MAPK1, tumor necrosis factor, TP53, vascular endothelial growth factor, and epidermal growth factor. These act mainly on the fluid shear stress, atherosclerosis, IL-17, hypoxia-inducible factor-1, and nonalcoholic fatty liver disease pathways, among others, which control immune inflammation, cell proliferation, and apoptosis. Based on molecular docking results, the active components of CBP bind well to its key targets. Conclusion: Our results indicated that CBP was effective for treating AD by reducing the expression of inflammatory factors, promoting cell proliferation and differentiation, and preventing nerve cell death and anti-neuronal cell apoptosis.

关键词： Alzheimer's disease Bai-Shao Chai-Hu molecular docking network pharmacology

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αDecay in extreme laser fields within a deformed Gamow-like model

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Nuclear Science and Techniques 2024年第2期35卷 131-144页

作者： Qiong Xiao Jun-Hao Cheng Yang-Yang Xu You-Tian Zou Jun-Gang Deng tong-Pu yu Department of Physics National University of Defense TechnologyChangsha 410073China College of Science China Three Gorges UniversityYichang 443002China

In this study, the effect of extreme laser fields on the α decay process of ground-state even–even nuclei was investigated.Using the deformed Gamow-like model, we found that state-of-the-art lasers can cause a slight change in the α decay penetration probability of most nuclei. In addition, we studied the correlation between the rate of change of the α decay penetration probability and angle between the directions of the laser electric field and α particle emission for different nuclei. Based on this correlation, the average effect of extreme laser fields on the half-life of many nuclei with arbitrary α particle emission angles was calculated. The calculations show that the laser suppression and promotion effects on the α decay penetration probability of the nuclei population with completely random α particle-emission directions are not completely canceled.The remainder led to a change in the average penetration probability of the nuclei. Furthermore, the possibility of achieving a higher average rate of change by altering the spatial shape of the laser is explored. We conclude that circularly polarized lasers may be helpful in future experiments to achieve a more significant average rate of change of the α decay half-life of the nuclei population.

关键词： αDecay Deformed Gamow-like model Half-lives Extreme laser field Penetration probability

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Esophageal cancer screening,early detection and treatment:Current insights and future directions

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1180-1191页

作者： Hong-Tao Qu Qing Li Liang Hao Yan-Jing Ni Wen-yu Luan Zhe Yang Xiao-Dong Chen tong-tong Zhang Yan-Dong Miao Fang Zhang Department of Emergency Yantai Mountain HospitalYantai 264000Shandong ProvinceChina Cancer Center Yantai Affiliated Hospital of Binzhou Medical UniversityThe 2nd Medical College of Binzhou Medical UniversityYantai 264100Shandong ProvinceChina

Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

关键词： Esophageal cancer Screening Early detection Treatment Endoscopic mucosal resection Endoscopic submucosal dissection

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DMT:A model detecting multispecies of tea buds in multi-seasons

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International Journal of Agricultural and Biological Engineering 2024年第1期17卷 199-208页

作者： Taojie yu Jianneng Chen Zhiwei Chen Yatao Li Junhua tong Xiaoqiang Du School of Mechanical Engineering Zhejiang Sci-Tech UniversityHangzhou 310018China Key Laboratory of Transplanting Equipment and Technology of Zhejiang Province Hangzhou 310018China

In China,tea products made from fresh leaves characterized by one leaf with one bud(1L1B)are classified as“Famous Tea”,which has better taste and higher economic value,but suffers from a labor shortage.Aiming at picking automation,existing studies focus on visual detection of 1L1B,but algorithm validation is limited to a specific variety of tea sprouting in a certain harvest season at a certain location,which limits the engineering application of developed tea picking robots working in various natural tea fields.To address this gap,a deep learning model DMT(detecting multispecies of tea)based on YOLOX-S was proposed in this paper.The DMT network takes YOLOX-S as a baseline and adds ECA-Net to the CSP Darknet and FPN of YOLOX-S.The average precision(AP),precision,and recall of DMT are 94.23%,93.39%,and 88.02%,respectively,for detecting 1L1B sprouting in spring;93.92%,93.56%,and 87.88%,respectively,for detecting 1L1Bsprouting in autumn.These experimental results are better than those of the five current object detection models.After fine-tuning the DMT network with another dataset composed of multiple tea varieties,the DMT network can detect 1L1B for different varieties of tea in multiple picking seasons.The results can promote the engineering application of picking automation of fresh tea leaves.

关键词： tea buds detection model multispecies of tea multi-season

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Chinese Medicine Combined with Adjuvant Chemotherapy for Improving Myelosuppression in Colorectal Cancer Patients: A Systematic Review and Network Meta-Analysis

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Chinese Journal of Integrative Medicine 2024年第7期30卷 643-652页

作者： LI Rui ZHANG tong YAN Shao-hua YAN yun-zi DING Ya-cong WANG Yan-song YANG yu-fei Department of Oncology China Academy of Chinese Medical Sciences Xiyuan Hospital Department of Oncology Dongfang Hospital Beijing University of Chinese Medicine Graduate School Beijing University of Chinese Medicine

Objective: To assess the effectiveness of Chinese herbal medicine(CHM) combined with adjuvant chemotherapy on myelosuppression for colorectal cancer(CRC) patients using network meta-analysis(NMA). Methods: Literature searches in both international(PubMed, Embase, Web of Science, and Cochrane Library) and Chinese(China Science and Technology Journal Database, Wanfang Data, China National Knowledge Infrastructure) databases for relevant randomized controlled trials(RCTs) were conducted from inception until October 10, 2022. We included RCTs of patients who received CHM combined with chemotherapy, including FOLFOX, XELOX, FOLFIRI, and other relevant regimens in the CHM treatment group. The outcomes included the incidence of myelosuppression, leukopenia, hemoglobin reduction, and thrombocytopenia. Two reviewers independently screened the databases, extracted the data, and assessed the risk of bias and credibility of evidence. RevMan 5.4.1 software and STATA 14.0 were used to perform the NMA. Results: A total of 31 RCTs were included, published from 2008 to 2021 in Chinese. Among these, 2,314 participants comparing the following 9 CHMs were identified: Shengbai Recipe(SBR), Bazhen Decoction(BZD), Jianpi Jiedu Recipe(JJR), Jianpi Recipe(JR), Compound Cantharis Capsule(CCC), Zaofan Pill(ZFP), Guilu Erxian Gel(GL), Buzhong Tiaogan Decoction(BZ), and Qiamagu Capsule(QM). The results of NMA found an indirect comparison. Based on the surface under the cumulative ranking curve(SUCRA), the ZFP+ chemotherapy group had the lowest incidence of myelosuppression, with an odds ratio(OR) of 0.08 [95% confidence interval(CI): 0.01, 0.76], whereas the GL+ chemotherapy group had the lowest incidence of leukopenia, hemoglobin reduction, and thrombocytopenia, with an OR of 5.25(95% CI: 2.41, 11.43), 4.66(95% CI: 2.23, 9.72), and 0.27(95% CI: 0.13, 0.54), respectively. Moreover, BZD + chemotherapy could alleviate leukopenia, hemoglobin reduction, and thrombocytopenia(P<0.01). Pairwise comparison showed that there was no difference in the

关键词： Chinese herbal medicine colorectal cancer network meta-analysis systematic review myelosuppression chemotherapy

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