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Design and synthesis of 3＇-(prop-2-yn-1-yloxy)-biphenyl substituted cyclic acylguanidine compounds as BACE1 inhibitors

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Chinese Chemical Letters 2016年第6期27卷 961-963页

作者： jia-kuo liu Wei Gu Xiao-Rui Cheng Jun-Ping Cheng Ai-Hua Nie Wen-Xia Zhou Beijing Institute of Pharmacology and Toxicology Beijing 100850 China

Based on the lead compounds 1 and 2, a series of novel BACE1 inhibitors were designed and synthesized,among which compound 9h exhibited a 60 fold improvement in potency over the lead compound 1. This represents a good lead for the discovery of more promising BACE1 inhibitors for the potential treatment of AD. The result also showed that the prop-2-yn-1-yloxy is a suitable fragment for modification of cyclic acylguanidine BACE1 inhibitors.

关键词： Alzheimer’s disease BACE1 inhibitor Prop-2-yn-1-yloxy Cyclic acylguanidine

Design and synthesis of 5-cyclopropyl substituted cyclic acylguanidine compounds as BACE1 inhibitors

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Chinese Chemical Letters 2016年第10期27卷 1626-1629页

作者： jia-kuo liu Wei Gu Xiao-Rui Cheng Jun-Ping Cheng Ai-Hua Nie Wen-Xia Zhou Beijing Institute of Pharmacology and Toxicology Beijing100850China

By taking compound 1 as a lead, a series of 5-cyclopropyl substituted cyclic acylguanidine compounds were designed and synthesized as BACE1 inhibitors, compound 4d exhibited 84-fold improved inhibition efficiency than lead compound 1. The diphenyl fragment at the P3 position and the substituents at the second phenyl ring were essential for the compounds to achieve improved inhibition efficiency. This SAR studies provides new insights into the design and synthesis of more promising BACE1 inhibitors for the potential treatment of AD.

关键词： Alzheimer's diseaseBACE inhibitor SecretaseDrug discoveryCyclic acylguanidine

喜树碱在二甲亚砜和甲醇(或乙醇)混合溶剂中溶解度的测定和关联

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高校化学工程学报 2016年第5期30卷 999-1006页

作者：支娟娟徐家阔刘琼李涛任保增郑州大学化工与能源学院河南郑州450001 洛阳理工科技学院环境工程与化学学院河南洛阳471023

采用重量法测定了喜树碱（camptothecine,CPT）在二甲亚砜（dimethylsulfoxide,DMSO）＋甲醇（或乙醇）混合溶剂中的溶解度,温度范围是274.50-326.00 K。在混合溶剂中CPT的溶解度随温度的升高而增大,随混合溶剂中DMSO摩尔分数含量的增... 详细信息

采用重量法测定了喜树碱（camptothecine,CPT）在二甲亚砜（dimethylsulfoxide,DMSO）＋甲醇（或乙醇）混合溶剂中的溶解度,温度范围是274.50-326.00 K。在混合溶剂中CPT的溶解度随温度的升高而增大,随混合溶剂中DMSO摩尔分数含量的增大而增大。分别用修正Apelblat方程、λh方程和理想状态方程进行关联,关联效果令人满意,获得了相关模型参数。相对而言,λh方程关联的效果较好。根据溶解度数据和修正的Apelblat方程计算出溶解焓、溶解熵和吉布斯自由能。

关键词：喜树碱溶解度固液相平衡热力学参数

RGS4 promotes the progression of gastric cancer through the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition

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World Journal of Gastroenterology 2025年第2期31卷 113-127页

作者： Peng-Yu Chen Pei-Yao Wang Bang liu Yang-Pu jia Zhao-Xiong Zhang Xin liu Dao-Han Wang Yong-jia Yan Wei-Hua Fu Feng Zhu Department of General Surgery Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China Department of General Surgery Jincheng People’s HospitalJincheng 048000Shanxi ProvinceChina

BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G *** speci-fic effect of RGS,particularly RGS4,on the progression of gastric cancer(GC)is not yet *** To explore the role and underlying mechanisms of action of RGS4 in GC *** The prognostic significance of RGS4 in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with *** assays were employed to assess the carcinogenic impact of RGS4,and the mechanism of its possible influence was detected by western blot analysis.A nude mouse xenograft model was established to study the effects of RGS4 on GC growth in *** RGS4 was highly expressed in GC tissues compared with matched adjacent normal *** RGS4 expression was correlated with increased tumor-node-metastasis stage,increased tumor grade as well as poorer overall survival in patients with *** experiments demonstrated that RGS4 knockdown suppressed GC cell proliferation,migration and ***,xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor ***,RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase,phosphatidyl-inositol-3-kinase,and protein kinase B,decreased vimentin and N-cadherin,and elevated *** High RGS4 expression in GC indicates a worse prognosis and RGS4 is a prognostic ***4 influences tumor progression via the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition.

关键词： Gastric cancer Prognosis Regulator of G protein signaling 4 Focal adhesion kinase Epithelial-mesenchymal transition

Pretreatment red blood cell distribution width as a predictive marker for postoperative complications after laparoscopic pancreatoduodenectomy

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 143-157页

作者： Xian-Rang Cao Yin-Long Xu jia-Wei Chai Kai Zheng Jun-Jie Kong Jun liu Shun-Zhen Zheng Department of Liver Transplantation and Hepatobiliary Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina Department of Breast and Thyroid Surgery Shandong Provincial Maternal and Child Health Care HospitalJinan 250014Shandong ProvinceChina

BACKGROUND Red blood cell distribution width(RDW)is associated with the development and progression of various *** To explore the association between pretreatment RDW and short-term outcomes after laparoscopic pancreatoduodenectomy(LPD).METHODS A total of 804 consecutive patients who underwent LPD at our hospital between March 2017 and November 2021 were retrospectively *** between pretreatment RDW and clinicopathological characteristics and short-term outcomes were *** Patients with higher pretreatment RDW were older,had higher Eastern Cooperative Oncology Group scores and were associated with poorer short-term outcomes than those with normal *** pretreatment RDW was an independent risk factor for postoperative complications(POCs)(hazard ratio=2.973,95%confidence interval:2.032-4.350,P<0.001)and severe POCs of grade IIIa or higher(hazard ratio=3.138,95%confidence interval:2.042-4.824,P<0.001)based on the Clavien-Dino classification *** analysis showed that high pretreatment RDW was an independent risk factor for Clavien-Dino classi-fication grade IIIb or higher POCs,a comprehensive complication index score≥26.2,severe postoperative pancreatic fistula,severe bile leakage and severe *** pretreatment RDW was positively associated with the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and was negatively associated with albumin and the prognostic nutritional *** Pretreatment RDW was a special parameter for patients who underwent *** was associated with malnutrition,severe inflammatory status and poorer short-term *** could be a surrogate marker for nutritional and inflammatory status in identifying patients who were at high risk of developing POCs after LPD.

关键词： Biomarker Laparoscopic pancreatoduodenectomy Postoperative complication Red blood cell distribution width Short-term outcomes

Global trends and hotspots of type 2 diabetes in children and adolescents:A bibliometric study and visualization analysis

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World Journal of Diabetes 2025年第1期16卷 140-168页

作者： Fang-Shuo Zhang Hai-Jing Li Xue Yu Yi-Ping Song Yan-Feng Ren Xuan-Zhu Qian jia-Li liu Wen-Xun Li Yi-Ran Huang kuo Gao School of Acupuncture-Moxibustion and Tuina Beijing University of Chinese MedicineBeijing 100029China School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China

BACKGROUND Epidemiological surveys indicate an increasing incidence of type 2 diabetes mellitus(T2DM)among children and adolescents *** to rapid disease progression,severe long-term cardiorenal complications,a lack of effective treatment strategies,and substantial socioeconomic burdens,it has become an urgent public health issue that requires management and *** T2DM differs from adult *** a significant increase in our understanding of youth-onset T2DM over the past two decades,the related review and evidence-based content remain *** To visualize the hotspots and trends in pediatric and adolescent T2DM research and to forecast their future research *** This study utilized the terms“children”,“adolescents”,and“type 2 diabetes”,retrieving relevant articles published between 1983 and 2023 from three citation databases within the Web of Science Core Collection(SCI,SSCI,ESCI).Utilizing CiteSpace and VoSviewer software,we analyze and visually represent the annual output of literature,countries involved,and participating *** allows us to predict trends in this research *** analysis encompasses co-cited authors,journal overlays,citation overlays,time-zone views,keyword analysis,and reference analysis,*** A total of 9210 articles were included,and the annual publication volume in this field showed a steady growth *** United States had the highest number of publications and the highest *** United States also had the most research institutions and the strongest research *** global hot journals were primarily diabetes professional journals but also included journals related to nutrition,endocrinology,and *** analysis showed that research related to endothelial dysfunction,exposure risk,cardiac metabolic risk,changes in gut microbiota,the impact on comorbidities and outcomes,etc.,were emerging *** have maintained their popularity in this field,sugges

关键词： Child Adolescent Type 2 diabetes mellitus Bibliometrics Knowledge mapping Visualization CiteSpace VOSviewer

Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment

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Neural Regeneration Research 2025年第9期20卷 2598-2610页

作者： Yi Wang Yuning Li Yakun Gu Wei Ma Yuying Guan Mengyuan Guo Qianqian Shao Xunming Ji jia liu Department of Clinical Laboratory Beijing Bo’ai HospitalChina Rehabilitation Research CenterCapital Medical UniversityBeijingChina Beijing Institute of Brain Disorders Laboratory of Brain DisordersMinistry of Science and TechnologyCollaborative Innovation Center for Brain DisordersBeijing Advanced Innovation Center for Big Data-based Precision MedicineCapital Medical UniversityBeijingChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina

Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this *** aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive *** found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic *** addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic *** phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic ***,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein *** ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein *** together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.

关键词： biomarker high-density lipoprotein ischemic stroke phosphorylatedα-synuclein poststroke cognitive impairment

Poorly controlled type II diabetes mellitus significantly enhances postoperative chemoresistance in patients with stage III colon cancer

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World Journal of Gastroenterology 2025年第3期31卷 29-41页

作者： Ruo-Yu Guan jia-Wei Wu Zi-Yun Yuan Zhi-Yuan liu Zi-Zhu liu Zhi-Cong Xiao Jing-Hui Li Cheng-Zhi Huang Jun-jiang Wang Xue-Qing Yao Guangdong Cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080Guangdong ProvinceChina Department of Gastrointestinal Surgery Department of General SurgeryGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080Guangdong ProvinceChina Department of General Surgery Guangdong Provincial People’s Hospital Ganzhou Hospital(Ganzhou Municipal Hospital)Ganzhou 341000Jiangxi ProvinceChina Shantou University Medical College Shantou 515041Guangdong ProvinceChina School of Medicine South China University of TechnologyGuangzhou 510006Guangdong ProvinceChina Gannan Medical University Ganzhou 341000Jiangxi ProvinceChina

BACKGROUND Type II diabetes mellitus(T2DM)has been associated with increased risk of colon cancer(CC)and worse prognosis in patients with *** effects of T2DM on postoperative chemoresistance rate(CRR)and long-term disease-free survival(DFS)and overall survival(OS)in patients with stage III CC who receive curative resection remain *** To investigate whether T2DM or glycemic control is associated with worse postoperative survival outcomes in stage III *** This retrospective cohort study included 278 patients aged 40-75 years who underwent surgery for stage III CC from 2018 to *** on preoperative T2DM history,the patients were categorized into non-DM(n=160)and DM groups(n=118).The latter was further divided into well-controlled(n=73)and poorly controlled(n=45)groups depending on the status of glycemic ***,OS,and CRR were compared between the groups and Cox regression analysis was used to identify risk *** Patients in the DM and non-DM groups demonstrated similar DFS,OS,and CRR(DFS:72.03%vs 78.75%,P=0.178;OS:81.36%vs 83.12%,P=0.638;CRR:14.41%vs 7.5%,P=0.063).Poorly controlled DM was associated with a significantly worse prognosis and higher CRR than well-controlled DM(DFS:62.22%vs 78.07%,P=0.021;OS:71.11%vs 87.67%,P=0.011;CRR:24.40%vs 8.22%,P=0.015).High preoperative fasting plasma glucose[DFS:Hazard ratio(HR)=2.684,P<0.001;OS:HR=2.105,P=0.019;CRR:HR=2.214,P=0.005]and glycosylated hemoglobin levels(DFS:HR=2.344,P=0.006;OS:HR=2.119,P=0.021;CRR:HR=2.449,P=0.009)indicated significantly poor prognosis and high CRR,while T2DM history did not(DFS:HR=1.178,P=0.327;OS:HR=0.933,P=0.739;CRR:HR=0.997,P=0.581).CONCLUSION Increased preoperative fasting plasma glucose and glycosylated hemoglobin levels,but not T2DM history,were identified as risk factors associated with poor postoperative outcomes and high CRR in patients with stage III CC.

关键词： Colon cancer Chemoresistance Diabetes mellitus Prognosis Type II diabetes mellitus

Sine oculis homeobox homolog family function in gastrointestinal cancer:Progression and comprehensive analysis

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World Journal of Clinical Oncology 2025年第1期16卷 10-24页

作者： Yang-Zheng Lan Zheng Wu Wen-jia Chen Xin-Ning Yu Hua-Tao Wu Jing liu Department of The Breast Center Cancer Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina Department of General Surgery First Affiliated Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina

The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including *** six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX *** or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular *** to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor *** the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic ***,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular *** conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.

关键词： Sine oculis homeobox homolog Gastrointestinal cancer Transcription factor Development Regulation Diagnosis Therapeutics