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Value of gamma-glutamyltranspeptidase-to-platelet ratio in diagnosis of hepatic fibrosis in patients with chronic hepatitis B

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World Journal of Gastroenterology 2017年第41期23卷 7425-7432页

作者： Yan-Chao Hu Hao Liu Xiao-Yan Liu Li-Na Ma Yu-hua guan Xia Luo Xiang-Chun Ding Department of Infectious Diseases General Hospital of Ningxia Medical University Department of Gastroenterology General Hospital of Ningxia Medical University

AIM To investigate the value of the gamma-glutamyltraspeptidase(GGT)-to-platelet(PLT) ratio(GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B(CHB). METHODS We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase(AST)-to-PLT ratio index(APRI), and fibrosis-4(FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin(TBil), alanine aminotransferase(ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic(ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients. RESULTS The GPR, APRI, and FIB-4 were not correlated withCHB patients' age, gender, or disease duration(P > 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count(P < 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis(P < 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI(F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4 were connected in

关键词： Gamma-glutamyltraspeptidase-to-platelet ratio APRI FIB-4 Chronic hepatitis B Hepatic fibrosis

Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer＇s disease

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Chinese Journal of Natural Medicines 2018年第1期16卷 53-62页

作者： PANG Xiao-Cong KANG De FANG Jian-Song ZHAO Ying XU Lv-Jie LIAN Wen-Wen LIU Ai-Lin DU guan-hua Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China Beijing Key Laboratory of Drug Target and Screening Research Beijing 100050 China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing 100050 China Institute of Clinical Pharmacology Guangzhou University of Chinese Medicine Guangzhou 510006 China

Naodesheng(NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease(AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.

关键词： Alzheimer’s disease Network pharmacology Docking Pharmacophore Machine learning

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药理学发展促进新药研发

中国药理学与毒理学杂志 2016年第12期30卷 1243-1249页

作者：杜冠华中国医学科学院药物研究所北京市药物靶点研究与新药筛选重点实验室中国药理学会北京100050

药理学是连接医学与药学、基础与临床、生命科学与化学及材料科学等多学科的一门桥梁学科。药理学与多个学科有着密切的联系,是医药科学中不可或缺的重要学科,在医药科学的发展中始终发挥着重要作用。药理学学科发展的任务主要有合理用... 详细信息

药理学是连接医学与药学、基础与临床、生命科学与化学及材料科学等多学科的一门桥梁学科。药理学与多个学科有着密切的联系,是医药科学中不可或缺的重要学科,在医药科学的发展中始终发挥着重要作用。药理学学科发展的任务主要有合理用药、新药研发和促进医药科学和生命科学的进步3个方面。在新药研发的整个过程中,药理学发挥了积极作用;重视药理学的发展是保障新药研发的关键条件。从药物靶点和作用机制研究到药物发现、药理作用到有效性认识、药物体内过程评价到安全性评价及临床研究到指导临床应用,都是药理学研究的内容。因此,药理学对于促进新药研发、保障合理用药具有十分重要的意义。

关键词：药理学新药研发合理用药

10-Hertz squeezed light source generation on the cesium D_(2)line using single photon modulation

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Frontiers of physics 2023年第3期18卷 167-174页

作者： guan-hua Zuo Yu-Chi Zhang Gang Li Peng-Fei Zhang Peng-Fei Yang Yan-Qiang Guo Shi-Yao Zhu Tian-Cai Zhang State Key Laboratory of Quantum Optics and Quantum Optics Devices Collaborative Innovation Center of Extreme OpticsInstitute of Opto-ElectronicsShanxi UniversityTaiyuan 030006China College of Physics and Electronic Engineering Shanxi UniversityTaiyuan 030006China Department of Physics Zhejiang UniversityHangzhou 310027China Key Laboratory of Advanced Transducers and Intelligent Control System Ministry of Education and Shanxi ProvinceCollege of Physics and OptoelectronicsTaiyuan University of TechnologyTaiyuan 030024China

Generation of squeezed light source is a promising technique to overcome the standard quantum limit in precision ***,we demonstrate an experimental generation of quadrature squeezing resonating on the cesium D_(2)line down to 10 Hz for the first *** maximum squeezing in audio frequency band is 5.57 ***,we have presented a singlephoton modulation locking to control the squeezing angle,while effectively suppressing the influence of laser noise on low-frequency *** whole system operates steadily for *** generated low-frequency squeezed light source can be applied in quantum metrology,light–matter interaction investigation and quantum memory in the audio frequency band and even below.

关键词： squeezed state optical parametric amplifier low-frequency squeezing

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NEXO Alpha 扬声器系统

电声技术 2001年第2期25卷 58-64页

作者： LIN hua-guan

1 引言 Alpha系统的雏形仅仅包括中/高频扬声器和一个2×18英寸低频扬声器。18英寸带通系统和10英寸驱动器号筒高频系统所组成的扬声器系统,分频点对整个系统的好坏起关键作用,而对这个分频点的处理对力素的开发者来说确实是一件头痛的... 详细信息

1 引言 Alpha系统的雏形仅仅包括中/高频扬声器和一个2×18英寸低频扬声器。18英寸带通系统和10英寸驱动器号筒高频系统所组成的扬声器系统,分频点对整个系统的好坏起关键作用,而对这个分频点的处理对力素的开发者来说确实是一件头痛的事情。从其它扬声器系统可知,就声音和最大声压级而言,分频区是这种组合系统的弱点所在。力素却找到了对策,他们开发了B1音箱来弥补这一缺陷。B1是一个15英寸号筒式低音反射系统,能够产生强劲的效果和冲击力,低频下限可以达到40 Hz左右。

关键词：扬声器 Alpha系统音响

Salvianolic acid A attenuates isoproterenol-induced myocardial infarction in mice through PI3K/Akt signal pathway

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中国药理学与毒理学杂志 2016年第10期30卷 1005-1006页

作者： FANG Lian-hua NIU Zi-ran CHEN Yu-cai YUAN Tian-yi LI Li WANG Shou-bao WANG Yue-hua LYU Yang DU guan-hua Beijing Key Laboratory of Drug Targets Identification and Drug Screening Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College Beijing Key Laboratory of Polymorphic Drugs Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible *** The mice were subcutaneously injected with isopropranol(ISO 8 mg·kg-1)to induce myocardial infarction and evaluated the myocardial protective effect of Sal A from mortality rate,electrocardiogram(ECG),heart function,myocardial infarction index,serum myocardial enzymes and explored its possible mechanisms from inflammatory,antioxidant and cells *** Sal A can dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardial protection *** results showed that Sal A can reduce the expression of myocardial inflammatory cytokines such as IL-6,TNF-α.Western blotting confirmed that Sal A can increase the expression of anti-apoptotic proteins Bcl-2,reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and *** Sal A have displayed significant protective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to increasing of PI3K/Akt signal pathway and inhibition of cell apoptosis and inflammatory reaction.

关键词： salvianolic acid A isoproterenol myocardial infarction apoptosis inflammation signaling pathway

表面序电极化、挠曲电极化与向列液晶盒饱和点的双稳态

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物理学报 2011年第1期60卷 454-461页

作者：关荣华华北电力大学数理学院保定071003

理论分析和数值模拟相结合,研究了表面序电极化、挠曲电极化对非对称弱锚定向列液晶盒在饱和点双稳态的影响,得到了两种极化共存时液晶指向矢满足的方程和边界条件.通过引入新的状态参量,从能量的角度对两种极化的物理效应进行了分析.... 详细信息

理论分析和数值模拟相结合,研究了表面序电极化、挠曲电极化对非对称弱锚定向列液晶盒在饱和点双稳态的影响,得到了两种极化共存时液晶指向矢满足的方程和边界条件.通过引入新的状态参量,从能量的角度对两种极化的物理效应进行了分析.结果表明,在一定条件下,两种极化耦合,在饱和点通过改变锚定能影响边界条件,从而诱导双稳态.文中给出了判断是否存在双稳态的一般条件,此条件与数值计算结果符合.

关键词：表面序电极化挠曲电极化饱和点双稳态

Inhibition of acetylcholinesterase by two genistein derivatives:kinetic analysis,molecular docking and molecular dynamics simulation

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Acta Pharmaceutica Sinica B 2014年第6期4卷 430-437页

作者： Jiansong Fang Ping Wu Ranyao Yang Li Gao Chao Li Dongmei Wang Song Wu Ai-Lin Liu guan-hua Du Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Target Research and Drug Screening Beijing 100050China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing 100050China

In this study two genistein derivatives(G1 and G2)are reported as inhibitors of acetylcholinesterase(AChE)and butyrylcholinesterase(BuChE),and differences in the inhibition of AChE are *** they differ in structure by a single methyl group,the inhibitory effect of G1(IC50¼264 nmol/L)on AChE was 80 times stronger than that of G2(IC50¼21,210 nmol/L).Enzyme-kinetic analysis,molecular docking and molecular dynamics(MD)simulations were conducted to better understand the molecular basis for this *** results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of *** predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area(MM/GBSA)method were consistent with the experimental *** analysis of the individual energy terms suggested that a difference between the net electrostatic contributions(ΔEele+ΔGGB)was responsible for the binding affinities of these two ***,analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124,Glu292,Val294 and Phe338 of *** conclusion,the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds.

关键词： Genistein derivatives Acetylcholinesterase(AChE) Kinetics analysis Molecular docking Molecular dynamics simulation MM/GBSA

Inhibition of chemokine-like factor 1 improves bloodbrain barrier dysfunction in rats following focal cerebral ischemia

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中国药理学与毒理学杂志 2016年第10期30卷 1024-1025页

作者： KONG Ling-lei HU Jin-feng YUAN Yu-he CHEN Nai-hong DU guan-hua State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College Beijing Key Laboratory of Drug Target and Screening Research Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion *** Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery *** water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were *** After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral ***-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and *** results suggest that CKLF1 is involved in BBB disruption after *** Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.

关键词： chemokine-like factor 1 cerebral ischemia brain-blood barrier