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Genetic variant in a BaP-activated super-enhancer increases prostate cancer risk by promoting AhR-mediated FAM227A expression

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Journal of Biomedical Research 2024年第2期38卷 149-162,I0001-I0010页

作者： Lulu Fan Hao Wang Shuai Ben Yifei Cheng Silu Chen Zhutao Ding Lingyan Zhao Shuwei Li Meilin Wang Gong Cheng Department of Environmental Genomics Jiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Genetic Toxicology the Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Urology the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China

Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving *** studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor ***,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular *** the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics *** then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target ***,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate *** current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.

关键词： super-enhancer prostate cancer genetic variants AhR BaP FAM227A

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Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration Research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of Pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric medical Research center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular *** r,the causal relationship between hypertension and cerebral small vessel disease remains *** has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular *** hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and *** is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of *** review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive *** also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

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Actinidia chinensis polysaccharide interferes with the epithelial-mesenchymal transition of gastric cancer by regulating the nuclear transcription factor-κB pathway to inhibit invasion and metastasis

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Journal of Traditional Chinese Medicine 2024年第5期44卷 896-905页

作者： ZHANG Guangshun XU Xiaonan XU Chuyun LIAO Guanghui XU Hao LOU Zhaohuan ZHANG Guangji School of Pharmaceutical Sciences Zhejiang Chinese Medical University Key Labortary of Blood-stasis-toxin Syndrome of Zhejiang Province School of Basic medical Sciences Zhejiang Chinese Medical University Traditional Chinese Medicine "Preventing Disease" Wisdom health Project Research center of Zhejiang the First Affiliated Hospital of Zhejiang Chinese medical University

OBJECTIVE: To investigate the mechanisms of the effect of Actinidia chinensis polysaccharide(ACPS) on the invasion and metastasis of gastric cancer ***: BGC-823-Luc gastric cancer cells stably transfected with a luciferase gene were used to establish an insitutransplanted tumor mouse model. A live mouse imaging system was used to observe tumor growth, and hematoxylin and eosin staining was applied to analyze tissue histopathology. Transwell and scratch wound assays were performed to examine the invasive and migratory ability of BGC-823 cells. Immunofluorescence,confocal microscopy, immunohistochemistry, and Western blot assays were used to analyze the expressions of the nuclear transcription factor-κB(NF-κB)signaling pathway and epithelial-mesenchymal transition(EMT)-related ***: ACPS significantly inhibited the growth of subcutaneously transplanted BGC-823-Luc gastric cancer tumors in nude mice and reduced inflammatory cell infiltration in tumor tissues. ACPS inhibited Epidermal Growth Factor-induced invasion, migration, and morphological changes in the cytoskeleton of BGC-823cells. ACPS inhibited gastric cancer EMT and decreased the expression of matrix metallopeptidase 9, N-cadherin and p-NF-κB p65 in transplanted tumor tissues. ACPS inhibited the expression of matrix metalloproteinases and vascular adhesion factors in BGC-823 cells, promoted p65-NF-κB nuclear translocation, and regulated proteins associated with the NF-κB p65 ***: ACPS inhibited gastric cancer invasion and metastasis both in vivo and in vitro, which evidenced the inhibition of gastric cancer EMT via regulating the NF-κB inflammatory pathway.

关键词： Actinidia chinensis polysaccharide NF-kappa B epithelial-mesenchymal transition invasion neoplasm metastasis signal transduction stomach neoplasms

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The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes:findings from a prospective,nationwide,and multicenter registry

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Journal of Geriatric Cardiology 2024年第5期21卷 523-533页

作者： Rui FU Ying-Xuan ZHU Kong-Yong CUI Jin-Gang YANG Hai-Yan XU Dong YIN Wei-Hua SONG Hong-Jian WANG Cheng-Gang ZHU Lei FENG Wei WU Kai-HongCHEN Yan-Yan ZHAO Ye LU Ke-Fei DOU Yue-Jin YANG on behalf of the CAMI Registry Investigators Cardiometabolic Medicine center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina medical Research&Biometrics center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Coronary Heart Disease center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology Guangzhou Traditional Chinese Medical College First Affiliated HospitalGuangdong ProvinceChina Department of Cardiology Longyan Hospital First HospitalFujian ProvinceChina 不详

OBJECTIVES To evaluate the predictive value of fasting plasma glucose(FPG)for in-hospital mortality in patients with acute myocardial infarction(AMI)with different glucose metabolism *** We selected 5,308 participants with AMI from the prospective,nationwide,multicenter CAMI registry,of which 2,081 were diabetic and 3,227 were *** were divided into high FPG and low FPG groups according to the optim-al cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts,*** primary endpoint was in-hospital *** Overall,94 diabetic patients(4.5%)and 131 nondiabetic patients(4.1%)died during hospitalization,and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L,*** with individuals who had low FPG,those with high FPG were significantly associated with higher in-hospital mortality in diabet-ic cohort(10.1%vs.2.8%;odds ratio[OR]=3.862,95%confidence interval[CI]:2.542-5.869)and nondiabetic cohort(7.4%vs.1.7%;HR=4.542,95%CI:3.041-6.782).After adjusting the potential confounders,this significant association was not ***-more,FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic *** FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic *** This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mor-tality in AMI patients with and without *** might be useful to stratify patients with AMI.

关键词： patients fasting infarction

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Trends in oxycodone and oxycodone-containing analgesics administration for back pain in emergency departments in the USA(2007–2018)

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World Journal of Emergency Medicine 2024年第3期15卷 169-174页

作者： Jonathan Chabon Jemer Garrido Deanna Schreiber-Gregory Jefferson Drapkin Sergey Motov Department of Emergency Medicine Maimonides Medical CenterBrooklyn 11219USA

BACKGROUND:To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments(EDs) in the USA from 2007 to ***:Data were gathered from the National Hospital Ambulatory medical Care Survey(NHAMCS) from 2007 to *** study population included individuals of all ages presenting to USA *** NHAMCS reasons for visit and oxycodone drug ID codes were used to isolate patients with back *** main outcome was the proportion of oxycodone and oxycodone-containing analgesics prescribed for back pain in the EDs over the specified time ***:There was a relative decrease in the overall administration of oxycodone for back pain in the EDs by 62.3% from 2007(244,000 visits) to 2018(92,000 visits).The proportion of ED patients prescribed with oxycodone-containing analgesics for back pain increased among patients aged 45 years and older(from 43.8% to 57.6%),female patients(from 54.5% to 62.0%),black patients(from 22.5% to 30.4%),and Hispanic/Latino patients(from 9.4% to 19.6%).Oxycodone/acetaminophen was most prescribed and accounted for 90.2% of all oxycodone-containing analgesics in 2007,with a decrease to 68.5% in *** oxycodone was the second most prescribed medication,accounting for 6.1% in 2007 and 31.5% in ***:The overall number of oxycodone-containing analgesics decreased significantly from 2007 to ***,that number trended upward in 45-year-old and older,female,black,or Hispanic/Latino patients from 2007 to *** total amount of pure oxycodone increased significantly from 2007 to 2008.

关键词： Oxycodone Back pain Emergency department

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