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Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma
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作者 Li-Li Miao jing-wen wang +3 位作者 Hui-Hui Liu Shuai Gao Yu-Chen Fan Kai wang 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2024年第1期35-42,共8页
Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnosti... Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC. 展开更多
关键词 Hepatocellular carcinoma Glycine dehydrogenase DNA methylation Peripheral blood mononuclear cells
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Passive particles driven by self-propelled particle:The wake effect
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作者 郑凯选 汪静文 +1 位作者 王世锋 聂德明 《Chinese Physics B》 SCIE EI CAS CSCD 2024年第4期500-507,共8页
This work focuses on numerically studying hydrodynamic interaction between a passive particle and a self-propelled particle,termed a squirmer,by using a two-dimensional lattice Boltzmann method(LBM).It is found that t... This work focuses on numerically studying hydrodynamic interaction between a passive particle and a self-propelled particle,termed a squirmer,by using a two-dimensional lattice Boltzmann method(LBM).It is found that the squirmer can capture a passive particle and propel it simultaneously,provided the passive particle is situated within the squirmer's wake.Our research shows that the critical capture distance,which determines whether the particle is captured,primarily depends on the intensity of the squirmer's dipolarity.The stronger dipolarity of squirmer results in an increased critical capture distance.Conversely,the Reynolds number is found to have minimal influence on this interaction.Interestingly,the passive particle,when driven by the squirmer's wake,contributes to a reduction in the squirmer's drag.This results in a mutual acceleration for both particles.Our findings can provide valuable perspectives for formulating the principles of reducing the drag of micro-swimmers and help to achieve the goal of using micro-swimmers to transport goods without physical tethers. 展开更多
关键词 lattice Boltzmann method(LBM) self-propelled particles particle-laden flow
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Intracranial large artery embolism due to carotid thrombosis caused by a neck massager:A case report
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作者 Jie Pan jing-wen wang +3 位作者 Xiao-Feng Cai Ke-Feng Lu Zhen-Zhen wang Shun-Yuan Guo 《World Journal of Clinical Cases》 SCIE 2023年第11期2489-2495,共7页
BACKGROUND There are few reported cases of intracranial large artery embolism due to carotid thrombosis caused by a neck massager.Herein we report such a case.CASE SUMMARY A 49-year-old woman presented with left limb ... BACKGROUND There are few reported cases of intracranial large artery embolism due to carotid thrombosis caused by a neck massager.Herein we report such a case.CASE SUMMARY A 49-year-old woman presented with left limb weakness and dysarthria after a history of neck massage for 1 mo.Neurological examination showed left central facial paralysis and left hemiparesis with a National Institutes of Health Stroke Scale score of 12.Brain magnetic resonance imaging revealed restricted diffusion on diffusion-weighted imaging in the right parietal and temporal lobes.Computed tomography angiography(CTA)indicated M3 segment embolism of the right middle cerebral artery.Neck CTA revealed thrombosis of the bilateral common carotid arteries.Carotid ultrasound showed thrombosis in the bilateral common carotid arteries(approximately 2 cm below the proximal end of the carotid sinus),and contrast-enhanced ultrasound did not suggest enhancement.No hypertension,diabetes,heart disease,vasculitis,or thrombophilia was found after admission.After 1 wk of treatment with aspirin 200 mg and atorvastatin 40 mg,a carotid ultrasound reexamination showed that the thrombosis had significantly reduced.CONCLUSION Neck massager may cause carotid artery thrombosis. 展开更多
关键词 Neck massager Carotid thrombosis formed Intracranial large artery
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人工智能在眼前段疾病诊治中的应用 被引量:1
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作者 王静文 徐雯 《国际眼科杂志》 CAS 北大核心 2022年第5期721-725,共5页
近年来,人工智能(AI)的蓬勃发展促进了其在医疗保健领域的推广与应用,同时也促进了医疗保健技术的革新与进步,尤其是在图像识别领域发挥出了无可替代的作用。眼科疾病的诊断十分依赖图像识别,AI在眼前段疾病的诊治方面取得了令人瞩目的... 近年来,人工智能(AI)的蓬勃发展促进了其在医疗保健领域的推广与应用,同时也促进了医疗保健技术的革新与进步,尤其是在图像识别领域发挥出了无可替代的作用。眼科疾病的诊断十分依赖图像识别,AI在眼前段疾病的诊治方面取得了令人瞩目的成果,如感染性角膜炎的分类、圆锥角膜的筛查、晶状体混浊程度的分级、白内障手术视频的自动分期、白内障术后屈光状态的预测、闭角型青光眼的诊断等。AI有望帮助解决目前临床存在的诸多难题,实现对疾病的早期诊治,但也存在着黑箱过程难以解释、缺少公共数据集、算法过于复杂等问题。本文概述了AI在眼前段疾病中的应用现状,分析目前存在的不足以及未来的发展前景。 展开更多
关键词 人工智能 机器学习 深度学习 眼前段疾病
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Association between TNF-a and IL-1β genotypes vs Helicobacter pylori infection in Indonesia 被引量:5
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作者 Yang Zhao jing-wen wang +10 位作者 Tsutomu Tanaka Akihiro Hosono Ryosuke Ando Shinkan Tokudome Soeripto FX Ediati Triningsih Tegu Triono Suwignyo Sumoharjo EY Wenny Astuti Achwan Stephanus Gunawan Yu-Min Li 《World Journal of Gastroenterology》 SCIE CAS 2013年第46期8758-8763,共6页
AIM:To investigate the correlation between the Helicobacter pylori(H.pylori)infection and host genetic background of healthy populations in Indonesia.METHODS:In March 2007,epidemiological studies were undertaken on th... AIM:To investigate the correlation between the Helicobacter pylori(H.pylori)infection and host genetic background of healthy populations in Indonesia.METHODS:In March 2007,epidemiological studies were undertaken on the general population of a city in Indonesia(Mataram,Lombok).The participants included 107 men and 187 women,whose ages ranged from6 to 74 years old,with an average age of 34.0(±14.4)(±SD).The H.pylori of subject by UBT method determination,and through the polymerase chain reaction with confronting two-pair primers(PCR-CTPP)method parsing the single nucleotide polymorphism of interleukin(IL)-8,IL-4,IL-1β,CD14,tumor necrosis factor(TNF-a)and tyrosine-protein phosphates non-receptor type 11(PTPN11)genotypes.The experimental data were analyzed by the statistical software SAS.RESULTS:The H.pylori infection rates in the healthy Indonesian population studied were 8.4%for men and12.8%for women;no obvious differences were noted for H.pylori infection rates by sex or age.TC genotypes of IL-4,TC and CC genotypes of TNF-a,and GA genotypes of PTPN11,were higher in frequency.Both CC and TC genotype of TNF-a T-1031C loci featured higher expressions in the healthy Indonesian population Indonesia studied of(OR=1.99;95%CI:0.67-5.89)and(OR=1.66;95%CI:0.73-3.76),respectively.C allele of IL-1βT-31C gene locus was at a higher risk(OR=1.11;95%CI:0.70-1.73)of H.pylori infection,but no statistical significance was found in our study.CONCLUSION:We reveal that the association between the TNF-a and IL-1βgenotypes may be the susceptibility of H.pylori in the studied population. 展开更多
关键词 HELICOBACTER PYLORI Tumor NECROSIS factor INTERLEUKIN-1Β Infection ALLELE
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Investigation of regulating rheological properties of water-based drilling fluids by ultrasound 被引量:1
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作者 Wei-An Huang jing-wen wang +4 位作者 Ming Lei Gong-Rang Li Zhi-Feng Duan Zhi-Jun Li Shi-Fu Yu 《Petroleum Science》 SCIE CAS CSCD 2021年第6期1698-1708,共11页
Regulating rheological properties of water-based drilling fluids has always been a hot topic.This paper proposed a new method for regulating rheological properties of water-based drilling fluids by ultrasonic field.Th... Regulating rheological properties of water-based drilling fluids has always been a hot topic.This paper proposed a new method for regulating rheological properties of water-based drilling fluids by ultrasonic field.The experimental results showed that the ultrasound increased the viscosity and yield point of bentonite suspension by reducing the particle size of clay,destroying the network structure between clay particles,increasing the mud yield and the cation exchange capacity of bentonite,and promoting the hydration dispersion of bentonite.The change of rheological property showed a memory effect at room temperature and high temperature.Besides,the ultrasonic energy affected the network structure between clays and polymer chains,thus regulating the rheological properties of the bentonite-polymer system.For two types of drilling fluids investigated,the rheology of the poly-sulfonate drilling fluid was regulated by damaging the grid structure between additives and clays by low-power ultrasound and reducing the clay particle size by high-power ultrasound,while the rheology of the deep-water drilling fluid was mainly regulated by disentangling the spatial grid structure between additives.Additionally,ultrasound showed no effect on the lubricity,inhibition and stability of drilling fluids,which proved the feasibility of ultrasound to regulate rheological properties of water-based drilling fluids. 展开更多
关键词 ULTRASOUND SUSPENSION Water-based drilling fluid Rheological property
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Oral myiasis after cerebral infarction in an elderly male patient from southern China:A case report 被引量:1
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作者 Tie-Zhu Zhang Ying Jiang +2 位作者 Xin-Tong Luo Rui Ling jing-wen wang 《World Journal of Clinical Cases》 SCIE 2020年第24期6499-6503,共5页
BACKGROUND Myiasis is a rare but risky pathology caused by a parasitic infestation of humansand animals by the dipterous larva. Oral myiasis occurs when soft tissues of theoral cavity are invaded by the larvae of flie... BACKGROUND Myiasis is a rare but risky pathology caused by a parasitic infestation of humansand animals by the dipterous larva. Oral myiasis occurs when soft tissues of theoral cavity are invaded by the larvae of flies. It is not a common disease for thereason that the oral cavity is not easily reachable for the fly to lay eggs. But it cancause pain, infection, uncomfortable feeling when the worms move, tissuedestruction and/or even life-threatening hemorrhages.CASE SUMMARY We reported a case of oral myiasis after cerebral infarction in a 78-year-old malepatient from southern China (Guangdong Zhanjiang). As a result of cerebralinfarction, he suffered from right hemiplegia, mobility and mental decline forabout 3 mo. He had difficulty swallowing and was fed via a feeding tube. Hemostly engaged in mouth breathing and had poor oral and dental hygiene. Morethan 20 live larvae were collected from the patient’s oral cavity, which werelocalized in the maxillary gingiva, the mandibular gingiva and the tongue. Thepatient recovered after the routine oral cleaning, removal of maggots,debridement and anti-infection treatment.CONCLUSION Early diagnosis and treatment of this infestation are essential due to thebothersome symptoms, such as inflammation, intense anxiety over the larvaemovement, possible serious complications, etc. Clinical staff should be familiarwith this infestation, and this disease should be considered, especially inphysically and mentally disabled patients or those at significant risk for infection.Necessary measures, including good sanitation, personal and environmentalhygiene and special care should be adopted so as to prevent this disease. 展开更多
关键词 Oral myiasis Larva Oral cavity Cerebral infarction Case report
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High-Efficiency Quantum Routing in a Multi-Cross-Shaped Waveguide
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作者 黄劲松 王敬文 +1 位作者 王尧 李艳玲 《Chinese Physics Letters》 SCIE CAS CSCD 2019年第3期32-36,共5页
Efficiently routing the quantum signals between different channels is essential in a quantum multichannel network.We investigate the quantum routing in a multi-cross-shaped waveguide coupled to driven three-level syst... Efficiently routing the quantum signals between different channels is essential in a quantum multichannel network.We investigate the quantum routing in a multi-cross-shaped waveguide coupled to driven three-level systems.Numerical results show that the high routing capacity transferring from the input channel to the other channels can be explicitly enhanced by effective reflection potentials. The proposed system may be utilized as a scalable quantum device to control single-photon routing. 展开更多
关键词 CCA High-Efficiency QUANTUM ROUTING WAVEGUIDE
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Study on syndrome differentiation based on pharmacology of syndrome management system-a case of Qi and Yin deficiency syndrome
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作者 Wen-Jun wang Shao-Jie Huang +6 位作者 Juan-Li Zhang Yang Ma Fei Mu Yu-Cheng Liao jing-wen wang Ai-Dong Wen Yi Ding 《History & Philosophy of Medicine》 2020年第4期119-128,共10页
Taking the Qi and Yin deficiency syndrome as an example,the research method of pharmacology of syndrome management system was proposed.By means of text mining,systematic pharmacology and target analysis,to attempt to ... Taking the Qi and Yin deficiency syndrome as an example,the research method of pharmacology of syndrome management system was proposed.By means of text mining,systematic pharmacology and target analysis,to attempt to reveal the essence of the corresponding syndrome by studying the drugs and targets of Qi and Yin deficiency.Fourteen Chinese herbs treating Qi and Yin deficiency were retrieved and used more than 30 times,and 9,317 related targets were predicted.The common targets of action were 85.Topological analysis was carried out by using degree centrality,closeness centrality and betweenness centrality to confirm that estrogen receptor(ESR1),tumor necrosis factor(TNF),D(2)dopamine receptor(DRD2),vitamin D3 receptor(VDR),glucocorticoid receptor(NR3C1),acetylcholinesterase(ACHE)and endothelin-1(EDN1)were highly correlated with Qi and Yin deficiency syndrome.Through the target to find Qi and Yin deficiency syndrome corresponding to 17 categories of diseases.A new idea was provided for studying the biological essence of TCM clinical syndrome differentiation. 展开更多
关键词 Pharmacology of syndrome management system Data mining Qi and Yin deficiency syndrome Drug law
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基于个体化机器学习的原发性免疫性血小板减少症危重出血预测模型:一项全国前瞻性队列研究
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作者 Zhuo-Yu An Ye-Jun Wu +65 位作者 Yu Hou Heng Mei Wei-Xia Nong Wen-Qian Li Hu Zhou Ru Feng Jian-Ping Shen Jun Peng Hai Zhou Yi Liu Yong-Ping Song Lin-Hua Yang Mei-Yun Fang Jian-Yong Li Yun-Feng Cheng Peng Liu Ya-Jing Xu Zhao wang Yi Luo Zhen Cai Hui Liu jing-wen wang Juan Li Xi Zhang Zi-Min Sun Xiao-Yu Zhu Xin wang Rong Fu Liang Huang Shao-Yuan wang Tong-Hua Yang Li-Ping Su Liang-Ming Ma Xie-Qun Chen Dai-Hong Liu Hong-Xia Yao Jia Feng Hong-Yu Zhang Ming Jiang Ze-Ping Zhou Wen-Sheng wang Xu-Liang Shen Yangjin Baima Yue-Ying Li Qian-Fei wang Qiu-Sha Huang Hai-Xia Fu Xiao-Lu Zhu Yun He Qian Jiang Hao Jiang Jin Lu Xiang-Yu Zhao Ying-Jun Chang Tao Wu Yao-Zhu Pan Lin Qiu Da Gao A-Rong Jin Wei Li Su-Jun Gao Lei Zhang Ming Hou Xiao-Jun Huang Xiao-Hui Zhang on behalf of the National Cooperative ITP Working Group 《Science Bulletin》 SCIE EI CAS CSCD 2023年第18期2106-2114,M0004,共10页
原发性免疫性血小板减少症(ITP)中少见但至关重要的危重出血事件,给患者的预后、生活质量和治疗决策带来严重影响。尽管有一些研究探讨了ITP中与危重出血相关的风险因素,但目前尚缺乏大样本数据、大规模多中心研究结果以及针对ITP患者... 原发性免疫性血小板减少症(ITP)中少见但至关重要的危重出血事件,给患者的预后、生活质量和治疗决策带来严重影响。尽管有一些研究探讨了ITP中与危重出血相关的风险因素,但目前尚缺乏大样本数据、大规模多中心研究结果以及针对ITP患者致命出血事件的预测模型。本研究首次采用国际血栓与止血学会新提出的ITP致命出血标准,利用大样本数据开发了首个基于机器学习的在线应用,用于预测ITP患者的致命出血.研究中,我们使用中国各地大型多中心数据进行开发,并对全国39家医疗中心进行为期一年的外部测试,得到了较好的训练、验证和测试数据集预测能力该基于新算法的便捷网络工具能够快速识别ITP患者的出血风险,辅助临床决策,有望未来降低不良事件的发生。 展开更多
关键词 Critical bleeding Severe bleeding Immune thrombocytopenia Machine learning Prediction model
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Nucleic acid drug vectors for diagnosis and treatment of brain diseases
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作者 Zhi-Guo Lu Jie Shen +5 位作者 Jun Yang jing-wen wang Rui-Chen Zhao Tian-Lu Zhang Jing Guo Xin Zhang 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2023年第2期604-656,共53页
Nucleic acid drugs have the advantages of rich target selection,simple in design,good and enduring effect.They have been demonstrated to have irreplaceable superiority in brain disease treatment,while vectors are a de... Nucleic acid drugs have the advantages of rich target selection,simple in design,good and enduring effect.They have been demonstrated to have irreplaceable superiority in brain disease treatment,while vectors are a decisive factor in therapeutic efficacy.Strict physiological barriers,such as degradation and clearance in circulation,blood-brain barrier,cellular uptake,endosome/lysosome barriers,release,obstruct the delivery of nucleic acid drugs to the brain by the vectors.Nucleic acid drugs against a single target are inefficient in treating brain diseases of complex pathogenesis.Differences between individual patients lead to severe uncertainties in brain disease treatment with nucleic acid drugs.In this Review,we briefly summarize the classification of nucleic acid drugs.Next,we discuss physiological barriers during drug delivery and universal coping strategies and introduce the application methods of these universal strategies to nucleic acid drug vectors.Subsequently,we explore nucleic acid drug-based multidrug regimens for the combination treatment of brain diseases and the construction of the corresponding vectors.In the following,we address the feasibility of patient stratification and personalized therapy through diagnostic information from medical imaging and the manner of introducing contrast agents into vectors.Finally,we take a perspective on the future feasibility and remaining challenges of vector-based integrated diagnosis and gene therapy for brain diseases. 展开更多
关键词 TREATMENT DIAGNOSIS replace
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Intermolecular Stetter reaction of aromatic aldehydes with(E)-(2-nitrovinyl)cyclohexane induced by N-heterocyclic carbene and thiourea 被引量:1
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作者 Qing-Fang Cheng jing-wen wang +1 位作者 Qi-Fa wang Zhou Liu 《Chinese Chemical Letters》 SCIE CAS CSCD 2016年第7期1032-1035,共4页
Intermolecular Stetter reaction of aromatic aldehydes with(E)-(2-nitrovinyl)cyclohexane catalyzed by thiazolium A has been developed.The reaction rate and efficiency are profoundly impacted by the presence of thiourea... Intermolecular Stetter reaction of aromatic aldehydes with(E)-(2-nitrovinyl)cyclohexane catalyzed by thiazolium A has been developed.The reaction rate and efficiency are profoundly impacted by the presence of thiourea B.The reaction affords moderate to good yields of the Stetter product.Some factors influencing yield were discussed. 展开更多
关键词 反应速度 N-杂环卡宾 环己烷 芳香醛 硫脲 分子 诱导 催化
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Prognostic significance of locally invaded sites and tissue types in patients with nasal extranodal natura-killer/T-cell lymphoma: a single-center retrospective analysis
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作者 Ge-Hong Dong Yong Li +9 位作者 Ji-Yong Dong Xue Li Hong-Fei Wan Lei Yang jing-wen wang Li-Ping Gong Yi-Hua Zhao Hong Zhang Zi-Fen Gao Hong-Gang Liu 《Chinese Medical Journal》 SCIE CAS CSCD 2019年第11期1305-1313,共9页
Background:Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported ... Background:Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage Ⅰ/Ⅱ ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL. Methods: We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients5 overall survival (OS). Results: Of the 86 patients, 71(82.6%) experienced invasion of AS, 22(25.6%) of soft tissue, and 26(30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank X^2 = 1.177, P = 0.278);however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank x^2 = 4.105, P = 0.043) or brain involvement (Log rank x^2 = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank x^2 = 10.390, P = 0.001) or bones (Log rank x^2 = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [Cl]: 1.466-20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% Cl: 1.517-24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates. Conclusions: Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients. 展开更多
关键词 Lymphoma Natural KILLER cells T-CELL Neoplasm INVASIVENESS Prognosis
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The effect of NR4A1 on APP metabolism and tau phosphorylation
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作者 Li-Ge Zhao Ying Tang +3 位作者 Jia-Ze Tan jing-wen wang Guo-Jun Chen Bing-Lin Zhu 《Genes & Diseases》 SCIE 2018年第4期342-348,共7页
Alzheimer’s disease(AD)is characterized by senile plaques(SP)composed of b-amyloid protein(Ab)and neurofibrillary tangles(NFTs)composed of intracellular hyperphosphorylated tau.Recently,nuclear receptor subfamily 4 g... Alzheimer’s disease(AD)is characterized by senile plaques(SP)composed of b-amyloid protein(Ab)and neurofibrillary tangles(NFTs)composed of intracellular hyperphosphorylated tau.Recently,nuclear receptor subfamily 4 group A member 1(NR4A1)was implicated in synaptic plasticity,long-term memory formation,suggesting that it may play a role in the pathophysiology of AD.Here,we showed that the expression of NR4A1 was significantly increased in the hippocampus of APP/PS1 transgenic mice.In addition,NR4A1 overexpression in HT22 cells up-regulated APP and BACE1 levels,down-regulated ADAM10 expression,and promoted amyloidogenesis as indicated by decreased a-CTF levels and elevated b-CTF levels.Furthermore,a raised level of phospho-tau(p-tau,S396)was accompanied by p-GSK3b(S9)expression reducing,but total tau,p-tau(S262 and T231),CDK5 and ERK remained unchanged in NR4A1-overexpressing cells.Collectively,our results suggest that NR4A1 promotes the amyloidogenic processing of APP by regulating ADAM10 and BACE1 expression in HT22 cells;as well as NR4A1 accelerates tau hyperphosphorylation by GSK3b signal.Therefore,NR4A1 may play an important role in the pathogenesis of AD. 展开更多
关键词 Alzheimer’s disease(AD) ADAM10 BACE1 GSK3b NR4A1 TAU
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