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Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia

World Journal of Clinical Cases 2024年第18期12卷 3468-3475页

作者： Meng-Jiao Lin Shu-Bin Zou Bai-Xiang Zhu Three departments of cardiovascular medicine Harbin 242 HospitalHarbin 150066Heilongjiang ProvinceChina

BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction(HFrEF),irrespective of diabetes.However,dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear.AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia.METHODS We conducted a randomized,double-blind,placebo-controlled trial in 200 patients with CHF and hyperuricemia,with HFrEF and serum uric acid levels≥7 mg/dL(≥416μmol/L).The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months.The primary endpoint was the change in serum uric acid level from baseline to 24 months.Secondary endpoints included changes in left ventricular ejection fraction(LVEF),Nterminal pro-B-type natriuretic peptide(NT-proBNP),and quality of life(QoL)scores,as well as the incidence of cardiovascular death and hospitalization for heart failure.RESULTS At 24 months,dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL(71μmol/L)compared with placebo(95%CI:-1.5 to-0.9;Pcardiovascular death and hospitalization for heart failure by 35%(95%CI:15–50;P=0.002)compared with the placebo.Adverse events were similar between the two groups,except for a higher rate of genital infections in the dapagliflozin group(10%vs 2%,P=0.01).CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia.Therefore,dapagliflozin may be a useful therapeutic option for this high-risk population.

关键词： Dapagliflozin Hyperuricemia Chronic heart failure Sodium-glucose cotransporter-2 inhibitor Uric acid levels cardiovascular mortality

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Investigations of nuclear chirality at iThemba LABS

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Frontiers of physics 2024年第2期19卷 7-38页

作者： R.A.Bark E.A.Lawrie C.Liu S.Y.Wang iThemba Laboratory for Accelerator Based Sciences National Research FoundationP.O.Box 722Somerset-West 7129South Africa Department of Physics University of the Western CapePrivate Bag X177535BellvilleSouth Africa Shandong Provincial Key Laboratory of Optical Astronomy and Solar-Terrestrial Environment Institute of Space SciencesShandong UniversityWeihai 264209China

Progress in the studies of chirality in atomic nuclei at iThemba LABS is reviewed.New regions of chirality,around mass 80 and 190 have been discovered using the AFRODITE array,specifically in the nuclei^(74)As,^(78,80,82)Br,^(81)Kr,and^(193,194,198)Tl.Many phenomena have been observed,including multiple chiral bands in the same nucleus,the coexistence of octupole correlations and nuclear chirality,and the coexistence of pseudo spin and nuclear chirality.The best example of chiral degeneracy to date was found in ^(194)Tl.The level scheme of ^(106)Ag has been revisited and interpreted in terms of two-and four-quasiparticle bands.Investigations using the particle-rotor model have shown that the fingerprints of chirality in the two-quasiparticle system only can occur in an idealised model description.For systems with a higher number of quasiparticles,the calculations showed that nuclear chirality can persist.

关键词： chirality high-spin states particle-rotor model

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Exploration of the efficacy and mechanism of treating head wind disease with the combination change of ginger volatile oil and gingerol by using content-weighted network pharmacology technology

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TMR Modern Herbal Medicine 2024年第1期7卷 43-56页

作者： Wei-Xiang Wang Fei Yan Fei Luan Ya-Jun Shi Xiao-Fei Zhang Dong-Yan Guo Bing-Tao Zhai Jun-Bo Zou Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine foundation research College of PharmacyShaanxi University of Chinese MedicineXianyang 712046China

Background:Exploring the efficacy,potential components,and mechanism of the combination of ginger essential oil and gingerols in the treatment of head wind disease based on network pharmacology technology with content weight.Methods:The experimental groups were divided into:0:10,1:4,1:2,1:1,2:1,4:1,10:0.The relative content(Ri)of the chemical constituents of ginger's volatile oil was determined using gas chromatography-mass spectrometry(GC-MS).Additionally,the physicochemical and biological property parameters(LogP,MDCK,PPB,MW)of the components were considered.To assess the quantitative effect of the components,a grading score was performed,and the quantitative effect index(Ki)was calculated.Subsequently,the target effect index(Ti)was calculated by combining the component-target matching score(Fit score).Using these calculations,the target effect score A was determined under the influence of multiple components targeting different targets.Key targets with A≥1000 were identified.To predict the targets related to head wind disease,the Comparative Toxicogenomics Database(https://***/),Gene Cards(https://***/),and Disgenet database(https://***/)were utilized.The key targets,obtained from different proportions of ginger's volatile oil and gingerol,were intersected with the predicted targets.This facilitated network pharmacological analysis and verification of the efficacy.Results:The content of volatile oil in ginger demonstrated an impact on key targets associated with the volatile oil group.Each specific combination of volatile oil consistently activated distinct pathways,with variations stemming from changes in content.Experimental testing revealed that different combinations of ginger's volatile oil and gingerol effectively alleviated migraine symptoms in rats.Conclusion:Through the application of content-weighted network pharmacology technology and pharmacodynamic verification,it was determined that altering the ratio between ginger's volatile oil and gingerol leads to variations in potential targets and pathways

关键词： network pharmacology volatile oil of ginger weight of content head wind disease

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Progress of gaseous arsenic removal from flue gas by adsorption:Experimental and theoretical calculations

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Journal of Environmental Sciences 2024年第2期136卷 470-485页

作者： Xuelei Yan Qingzhu Li Xiaowei Huang Bensheng Li Shengtu Li Qingwei Wang School of Metallurgy and Environment Central South UniversityChangsha 410083China National Engineering research Centre for Control and Treatment of Heavy Metal Pollution Central South UniversityChangsha 410083China National Engineering research Center for Rare Earth Materials General Research Institute for Non-Ferrous MetalsBeijing 100088China

Because of its high mobility and difficult capture,gaseous arsenic pollution control has become the focus of arsenic pollution control.It mainly exists in the form of highly toxic As_(2)O_(3)in the flue gas.Therefore,removing gaseous As_(2)O_(3)from flue gas is of great practical significance for arsenic pollution control.Stabilizing gaseous As_(2)O_(3)on the surface of adsorbents by physical or chemical adsorption is an effective way to reduce the content of arsenic in the flue gas and alleviate arsenic pollution.Over the past few decades,various adsorbents have been developed to capture gaseous As_(2)O_(3)in the flue gas,and their adsorption mechanisms have been studied in detail.Thus,it is necessary to review the strategies of arsenic removal from flue gas by adsorption,which can inspire further research.Based on summarizing the morphological distribution of gaseous As_(2)O_(3)in the flue gas,this review further summarizes the removal of gaseous As_(2)O_(3)by several adsorbents and the effect of temperature and the main components of the flue gas on arsenic adsorption.In addition,the mechanism of arsenic removal based on adsorption in the flue gas is discussed in depth through theoretical calculations,which is the particular focus of this review.Finally,prospects based on the present research state of arsenic removal by adsorption are proposed to provide ideas for developing effective and stable adsorbents for arsenic removal from flue gas.

关键词： Gaseous arsenic Flue gas Adsorption Theoretical calculation Mechanism

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How variable progenitor clones construct a largely invariant neocortex

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National Science Review 2024年第1期11卷 129-144页

作者： Zhongfu Shen Jiajun Yang Qiangqiang Zhang Kuiyu Wang Xiaohui Lv Xiaolin Hu Jian Ma Song-Hai Shi New Cornerstone Science Laboratory IDG/McG overn Institute for Brain Research Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University Department of Computer Sciences Tsinghua University College of Life Sciences Nankai University Chinese Institute for Brain research

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors(RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.

关键词： neocortex radial glial progenitor intermediate progenitor neurogenesis clonal variability layer formation

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Protective effects of oleic acid and polyphenols in extra virgin olive oil on cardiovascular diseases

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Food Science and Human Wellness 2024年第2期13卷 529-540页

作者： Yan Lu Jun Zhao Qiqi Xin Rong Yuan Yu Miao Manli Yang Hui Mo Keji Chen Weihong Cong Laboratory of cardiovascular Diseases Xiyuan Hospital of China Academy of Chinese Medical SciencesBeijing 100091China National Clinical research Center for Chinese Medicine Cardiology Beijing 100091China Traditional Chinese Medicine Department The Aff iliated Hospital of Qingdao UniversityQingdao 266000China Nanjing University of Chinese Medicine Nanjing 210023China Health Bureau of the Government of the Macao Special Administrative Region Macao 999078China

The Mediterranean diet has long been recognized as one of the most effective ways to prevent and improve cardiovascular disease.Extra virgin olive oil(EVOO)is the typical sources of fat in the Mediterranean diet which have been shown to have noteworthy nutritional value and positive impact on human health.It is worth noting that EVOO owes its superior nutritional value to its bioactive composition.The main component of EVOO is monounsaturated fatty acids(MUFAs)in the form of oleic acid.Oleic acid accounts for up to 70%-80%of EVOO.Secondly,EVOO contains approximately more than 30 phenolic compounds,of which HT is essential for the protection against cardiovascular diseases.In this review,we focused on the potential mechanisms of oleic acid and polyphenols combat cardiovascular diseases risk in terms of oxidative stress,inflammation,blood pressure,endothelial function and cholesterol.This review might provide a reference for the studies on cardiovascular protective effects of EVOO.

关键词： cardiovascular diseases Extra virgin olive oil Oleic acid Polyphenols

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KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer’s disease

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World Journal of Psychiatry 2024年第3期14卷 445-455页

作者： Qun-Shan Lu Lin Ma Wen-Jing Jiang Xing-Bang Wang Mei Lu Department of Geriatric Medicine Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Key Laboratory of cardiovascular Proteomics of Shandong Province Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and

关键词： Alzheimer's disease Diabetes Insulin resistance KAT7 Dual-specificity tyrosine phosphorylation-regulated kinase-1A HMGN1

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Triglyceride-glucose index predicts the prognosis of patients with acute myocardial infarction

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South China Journal of Cardiology 2024年第1期25卷 11-20,43页

作者：伦梓恒何洁欣付明易诗欣张莹 Department of cardiovascular Medicine Guangdong Cardiovascular InstituteGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510180GuangdongChina

Background research has indicated that the triglyceride-glucose(Ty G)index is associated with the development and prognosis of cardiovascular diseases.However,there is still uncertainty regarding whether the Ty G index can predict adverse cardiovascular events in patients with acute myocardial infarction(AMI).The present study aimed to explore the prognostic value of the Ty G index in patients with AMI.Methods AMI patients who underwent emergency percutaneous coronary intervention(PCI)in Guangdong General Hospital from February 2021 to June 2022 were enrolled.The study population was grouped based on the median Ty G index.The end point of the study was major adverse cardiovascular events(MACEs),defined as all-cause mortality,cardiogenic shock,recurrent myocardial infarction,acute attack of heart failure,repeat revascularization induced by cardiac ischemia,and urgent visit due to aggravation of chest pain.The Ty G index was calculated as follows:LN[fasting triglycerides(mg/d L)×fasting blood glucose(mg/d L)x1/2].Results A total of 196 patients were included.In the multivariate logistic regression analysis,Ty G index[odds ratio(OR):0.99,95%confidence interval(CI):0.45-2.16,P=0.98]was not significantly correlated with the occurrence of MACEs in AMI patients during hospitalization.Afterwards a total of 178 patients were followed up for an average of 12.66±5.35 months.In the multivariate Cox proportional hazards model,Ty G index[hazard ratio(HR):1.91,95%CI:1.02-3.6,P<0.05]were independent predictor of adverse events during follow-up,and the area under the receiver operating characteristic(ROC)curve(AUC)was0.63(0.53-0.73,P<0.05).Conclusions Ty G index can independently predict the prognosis of AMI patients during the follow-up period.[S Chin J Cardiol 2024;25(1):11-20]

关键词： Triglyceride glucose index Acute myocardial infarction Prognosis

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Combustion mechanism of benzene in iron ore sintering process:experimental and simulation

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Journal of Iron and Steel research(International) 2024年第1期31卷 195-203页

作者： Zhi-gang Que Jin-ming Shi Xian-bin Ai Institute of Energy research Jiangxi Academy of ScienceNanchang330096JiangxiChina Jiangxi Carbon Neutralization research Center Nanchang330096JiangxiChina

Benzene is a typical component of volatile organic compounds(VOCs)in the iron ore sintering flue gas.The combustion behavior of benzene directly affects the emission of VOCs in iron ore sintering process.The effects of temperature,benzene,and oxygen concentrations on the conversion ratio of benzene were investigated by experiments and numerical simulation.The experiments were carried out in a tube reactor at temperatures of 773-1098 K,benzene concentrations of 0.01-0.03 vol.%,and oxygen concentrations of 10-21 vol.%.The numerical simulation was performed with the plug flow model in the CHEMKIN program based on a kinetic model that consists of 132 chemical species and 772 elementary step-like reactions.The experimental results reveal that increasing the temperature and benzene concentration could signifi-cantly promote benzene combustion.It is attributed to the increase in the reaction rates of all steps in the pathway for forming CO_(2)and H_(2)O.In addition,due to the large equivalent ratio of oxygen to benzene,the conversion ratio of benzene remained constant at different oxygen concentrations.The simulation results were in good agreement with the experimental results and indicated that six elementary reactions dominated the formations of CO_(2)and H_(2)O.The oxidations of C_(6)H_(5)O,CO,and C_(5)H_(4)O intermediates to CO_(2)were the limiting steps in the reaction pathways.

关键词： Benzene Volatile organic compound Iron ore sinter Combustion Simulation Temperature Oxygen

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Network Pharmacology-Based Dissection of the Bioactive Compounds and Pharmacological Mechanisms of Yiqi Fumai Lyophilized Injection for the Treatment of Heart Failure

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 75-82页

作者： Yu-Xi Huang Jing-Jing Fan Lu-Lu Xu Rong Yu Yi Kuang Yue Chai Rui Zheng Xiao-Yu Zhang Hong-Cai Shang Xue Qiao Min Ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijingChina Key Laboratory of Chinese Internal Medicine of Ministry of Education Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina Yunnan Baiyao International Medical research Center Peking UniversityBeijingChina Key Laboratory of Molecular cardiovascular Sciences of Ministry of Education Peking UniversityBeijingChina

Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood.Materials and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index calculation.Then,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays.Results:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets.Particularly,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF.YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and PI3K-Akt.The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats.Ginsenoside Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma.Conclusions:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF.Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.

关键词： Contribution index heart failure network pharmacology traditional Chinese medicine yiqi fumai lyophilized injection

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