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OCT1和ABCG2基因多态性与中国癫痫患者拉莫三嗪血药浓度相关性研究

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癫痫杂志 2016年第6期2卷 555-556页

作者： Shen CH Zhang YX Lu RY Jin B Wang S Liu ZR tang yl 丁美萍浙江大学附属第二医院神经内科杭州310009

背景拉莫三嗪(Lamotrigine,LTG)是新一代抗癫痫药物(Antiepileptic drugs,AEDs),广泛用于部分性和全面性癫痫的治疗.然而先前的研究已经观察到不同个体之间LTG药代动力学的显著差异,由于临床和环境等因素,遗传易感性对这些差异起到重要... 详细信息

背景拉莫三嗪(Lamotrigine,LTG)是新一代抗癫痫药物(Antiepileptic drugs,AEDs),广泛用于部分性和全面性癫痫的治疗.然而先前的研究已经观察到不同个体之间LTG药代动力学的显著差异,由于临床和环境等因素,遗传易感性对这些差异起到重要作用.研究发现单核苷酸多态性(Single nucleotidepolymorphisms,SNPs)如UGT1A4和UGT2 B7可能影响LTG的血药水平,多态转运蛋白如P-糖蛋白(P-glycoprotein,P-gp,由MDR1/ABCB1编码)、乳腺癌而耐药蛋白(Breast cancer resistance protein,BCRP,由ABCG2编码)和多药耐受蛋白(Multi-drug resistance protein 2,MRP,由ABCC2编码)的过表达对LTG治疗的药代动力学和生物利用度也产生影响.研究发现ABCB1 rs1128503和ABCG2 rs2231142的基因多态性与LTG单药治疗时的血药浓度有关.然而,另一ABCG2基因的变异(rs2231137)和ABCC2的作用并没有研究报道.作为流入转运体亚家族的有机阳离子转运体(Organic cation transporters,OCTs)在阳离子药物的分布和分泌中起到重要作用.肝细胞核因子4α(Hepatocyte nuclear factor 4 alpha,HNF4α)是肝组织内调节肝细胞发育和分化的因子,在人类和老鼠的肝脏中与多种基因启动子直接相连.有报道表明HNF4α rs2071197可能与LTG血药浓度相关,然而另一个SNP(HNF4α rs3212183)对于LTG血药浓度的作用并不甚清楚.

关键词：编码癫痫基因多态性蛋白血药浓度

Chemical Composition, Pharmacological Effects and Clinical Applications of Cinobufacini

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Chinese Journal of Integrative Medicine 2024年第4期30卷 366-378页

作者： ZUO Qian XU Ding-qiao YUE Shi-jun FU Rui-jia tang Yu-ping Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility Shaanxi University of Chinese MedicineXi'an(712046)China

Chinese medicine cinobufacini is an extract from the dried skin of Bufo bufo gargarizans Cantor,with active ingredients of bufadienolides and indole *** further research and clinical applications,it is found that cinobufacini alone or in combination with other therapeutic methods can play an anti-tumor role by controlling proliferation of tumor cells,promoting apoptosis,inhibiting formation of tumor neovascularization,reversing multidrug resistance,and regulating immune response;it also has the functions of relieving cancer pain and regulating immune *** this paper,the chemical composition,pharmacological effects,clinical applications,and adverse reactions of cinobufacini are ***,the extraction of monomer components of cinobufacini,the relationship between different mechanisms,and the causes of adverse reactions need to be further ***,high-quality clinical studies should be conducted.

关键词： cinobufacini chemical composition Chinese medicine pharmacological effect clinical application adverse effect

Mpox(formerly monkeypox):pathogenesis,prevention,and treatment

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Signal Transduction and Targeted Therapy 2024年第1期9卷 234-248页

作者： Junjie Lu Hui Xing Chunhua Wang Mengjun tang Changcheng Wu Fan Ye Lijuan Yin Yang Yang Wenjie Tan Liang Shen Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and ScienceHubei ProvinceXiangyang 441021China NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China College of Biotechnology Tianjin University of Science&TechnologyTianjin 300457China Shenzhen Key Laboratory of Pathogen and Immunity National Clinical Research Center for infectious diseaseState Key Discipline of Infectious DiseaseShenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China

In 2022,a global outbreak of Mpox(formerly monkeypox)occurred in various countries across Europe and America and rapidly spread to more than 100 countries and *** World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox ***,nations intensified their efforts to explore treatment strategies aimed at combating the infection and its ***,the available therapeutic options for Mpox virus infection remain *** far,only a few numbers of antiviral compounds have been approved by regulatory *** the high mutability of the Mpox virus,certain mutant strains have shown resistance to existing pharmaceutical *** highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of ***,there is a lack of comprehensive literature on the pathophysiology and treatment of *** address this issue,we conducted a review covering the physiological and pathological processes of Mpox infection,summarizing the latest progress of anti-Mpox *** analysis encompasses approved drugs currently employed in clinical settings,as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against ***,we have gained valuable insights from the process of Mpox drug development,including strategies for repurposing drugs,the discovery of drug targets driven by artificial intelligence,and preclinical drug *** purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.

关键词： prevention treatment intensified

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

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Neural Regeneration Research 2024年第3期19卷 642-649页

作者： Xiuling tang Tao Yan Saiying Wang Qingqing Liu Qi Yang Yongqiang Zhang Yujiao Li Yumei Wu Shuibing Liu Yulong Ma Le Yang Precision Pharmacy&Drug Development Center Department of PharmacyTangdu HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Clinical Pharmacy Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu ProvinceChina Department of Pharmacology School of PharmacyAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Anesthesiology The First Medical Center of Chinese PLA General HospitalBeijingChina Department of Anatomy Histology and Embryology and K.K.Leung Brain Research CentreAir Force Medical UniversityXi’anShaanxi ProvinceChina

β-Sitosterol is a type of phytosterol that occurs naturally in *** studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic *** we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced *** investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic *** addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its *** conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

关键词： apoptosis blood-brain barrier β-sitosterol cerebral ischemia/reperfusion injury cholesterol overload cholesterol transport endoplasmic reticulum stress ischemic stroke molecular docking NPC1L1

AIEgen configuration transition and aggregation enable dual prompt emission for single-component nondoped white OLEDs

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Aggregate

Aggregate 2024年第1期5卷 292-298页

作者： Jiasen Zhang Qiang Wei Wei Li Hao Chen Xiangyu Zhu Yongqi Bai Nannan Fei Liang Cao Zujin Zhao Anjun Qin Ben Zhong tang Ziyi Ge Zhejiang Provincial Engineering Research Center of Energy Optoelectronic Materials and Devices Ningbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingboP.R.China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijingP.R.China Center for Aggregation-Induced Emission State Key Laboratory of Luminescent Materials and Devices South China University of Technology GuangzhouGuangzhouChina Shenzhen Institute of Aggregate Science and Technology School of Science and EngineeringThe Chinese University of Hong KongShenzhenChina

The dual emission(DE)feature in materials holds great potential to revolutionize the development of one-component system white organic lightemitting diodes(WOLEDs).However,the reported DE materials remain scarce owing to the formidable challenge of breaking Kasha’s rule and managing the intricate energy/charge transfer ***,we have introduced a groundbreaking DE AIEgen,2CzAn-TPE,which possesses a simple structure and undergoes Z-to-E isomerization and exhibits yellow and red fluorescence powders for pre-and post-sublimation,*** relatively lower potential energy,Z-conformation((Z)-1,2-diphenyl-1,2-bis(4-(10-(9-phenyl-9H-carbazol-3-yl)anthracen-9-yl)phenyl)ethene)of 2CzAn-TPE can be readily transformed into E-conformation((E)-1,2-diphenyl-1,2-bis(4-(10-(9-phenyl-9Hcarbazol-3-yl)anthracen-9-yl)phenyl)ethene)via vacuum *** utilization of X-ray diffraction and grazing-incidence-wide-angle X-ray scattering techniques confirms the structural transformation,while the crystallographic analysis reveals the establishment of numerous intermolecular CH⋅⋅⋅πinteractions between the tetraphenylethene(TPE)moiety and both the anthracene and carbazole *** allows a densely packed molecular arrangement,thereby offering propitious conditions for excimer generation in the E-conformation aggregated *** utilizing the sublimated 2CzAn-TPE as an emitter,a nondoped one-component WOLED was prepared,exhibiting an exceptionally high external quantum efficiency(EQE)of 5.0%,which represents one of the highest performances among all *** research introduces a novel,simple,and efficient approach to realize highly efficient one-molecule WOLEDs.

关键词： aggregation-induced emission dual emission isomerization white OLED

Lycorine derivative effectively inhibits the replication of coronaviruses both in vitro and in vivo

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hLife 2024年第2期2卷 75-87页

作者： Liang Shen Jianzhong Zhao Ying Xia Junjie Lu Jiali Sun Jian tang Hui Xing Lijuan Yin Yang Yang Chunhua Wang Department of Clinical Laboratory Xiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceHubeiChina Shenzhen Key Laboratory of Pathogen and Immunity National Clinical Research Center for Infectious DiseaseState Key Discipline of Infectious DiseaseShenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyGuangdongChina Department of Clinical Laboratory Xiangyang No.1 People’s HospitalHubei University of MedicineHubeiChina State Key Laboratory of Food Nutrition and Safety Key Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science&TechnologyTianjinChina

The established and ongoing prevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and seasonal human coronaviruses(HCoV)like HCoV-OC43,HCoV-NL63,and HCoV-229E,pose a continuous threat to public ***,it is urgently needed to explore antiviral drugs with broad-spectrum anti-coronavirus *** previous studies have revealed that lycorine is a potent broad-spectrum anti-coronavirus drug,a natural alkaloid extracted from Amaryllidaceae with various pharmacological and microbiological ***,it is unsafe to directly use lycorine as a clinical antiviral drug due to the cytotoxicity and induction of cell *** this study,a series of lycorine derivatives were designed and *** of them,named Ly-8,was found to effectively inhibit the replication of different coronavirus strains in vitro,including ***,Ly-8 was also shown to effectively inhibit HCoVOC43 replication in the central nervous system,and provide effective protection against HCoV-OC43 infection in mice with low drug ***,Ly-8-resistant mutants were not observed during the 30 times sequential passages in cell ***,these findings suggest that Ly-8 may be a potential candidate drug for the future development of broad-spectrum anti-coronavirus drugs.

关键词： broad-spectrum antiviral drug lycorine derivative Ly-8

NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma

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Cancer Communications 2024年第2期44卷 251-272页

作者： Yue Yao Yi Xu Liang Yu Ting-Mao Xue Zhi-Jie Xiao Pui-Chi Tin Hiu-Ling Fung Hoi-tang Ma Jing-Ping Yun Judy Wai Ping Yam Department of Pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongP.R.China Department of Endocrinology and Metabolism Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China State Key Laboratory of Oncology in South China Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Hepatobiliary Surgery II Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China Scientific Research Center The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongP.R.China State Key Laboratory of Liver Research The University of Hong KongHong KongP.R.China Department of Pathology Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:Small extracellular vesicles(sEVs)mediate intercellular commu-nication that contributes to hepatocellular carcinoma(HCC)progression via multifaceted *** success of cell entry determines the effect of sEV on recipient ***,we aimed to delineate the mechanisms underlying the uptake of sEV in ***:AF,Alexa Fluor;ANOVA,analysis of variance;ATP9A,ATPase Phospholipid Transporting 9A;BCECF-AM,2’,7’-bis-(2-barboxyethyl)-5-(and-6)-carboxyfluorescein,acetoxymethyl ester;BSA,bovine serum albumin;CCMR,Centre for Comparative Medicine Research;CRISPR,clustered regularly interspaced short palindromic repeats;CTL,ctrl;CXCR4,C-X-C Chemokine Receptor Type 4;DAPI,4′,6-diamidino-2-phenylindole;DFS,disease-free survival;DMEM,Dulbecco’s Modified Eagle Medium;DMSO,dimethyl sulfoxide;Dox,doxycycline;EEA1,early endosome antigen 1;EIPA,5-(N-ethyl-N-isopropyl)-amiloride;FBS,fetal bovine serum;FITC,fluorescein isothiocyanate;GAPDH,glyceraldehyde-3-phosphate dehydrogenase;GM130,Golgi matrix protein 130;HCC,hepatocellular carcinoma;HEPES,4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;HPRT1,hypoxanthine phosphoribosyltransferase 1;H-score,histoscore;IAA,indole-3-acetic acid;KD,knockdown;KO,knockout;mAID,mini-auxin-inducible degron;MTT,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide;NHE7,Na(+)/H(+)exchanger 7;ns,non-significant;OD,optical density;OS,overall survival;PBS,phosphate-buffered saline;PCR,polymerase chain reaction;pHe,endosomal pH;pHi,intracellular pH;PKH67,Paul Karl Horan 67;Rab21,Ras-associated binding protein 21;RIPA,radioimmunoprecipitation assay;SAM,synergistic activation mediator;SEMs,standard error of the means;sEVs,small extracellular vesicles;sgRNA,single-guide RNA;shRNA,short-hairpin RNA;SLC9,solute carrier gene 9;SLiCE,Seamless Ligation Cloning Extract;TCGA,The Cancer Genome Atlas;TCL,total cell lysates;TGN,trans-Golgi network;TMA,tissue microarray;TMR,tetramethyl rhodamine;TSG101,tumor susceptibility gene *** Yao an

关键词： hepatocellular carcinoma small extracellular vesicles macropinocytosis pH regulation sodium-hydrogen exchanger

The formation age and evolution of Kumtagh Desert

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Journal of Arid Land 2011年第2期3卷 114-122页

作者： JinNian tang ZhiZhu SU Feng DING ShuJuan ZHU YouHao E XinWei ZHAI ZhiYu yl HuJun LIU JinChun ZHANGI FaMing LI Minqin National Studies Station for Desert Steppe Ecosystem Minqin 733300 China State key Laboratory Breeding Base of Desertification and Aeolian Sand Disaster Combating Gansu Desert Control ResearchInstitute Lanzhou 730070 China School of History and Culture Shanxi University Taiyuan 030006 China Lanzhou University Lanzhou 730000 China

The ancient aeolian sand has been regarded as an indicator for the formation and evolution of a desert in the *** Desert is located at the northern fringe of Qinghai-Tibet *** first integrated scientific investigation to the desert was carried out during the period of *** Desert is an ideal natural model for studying the formation and evolution of the desert because the Quaternary strata containing ancient aeolian sands are widely *** integrated field investigation and studies on sedimentary,chronology and palynology of typical profiles named Suosuo gully,Xiaoquan gully and gravel body with ancient aeolian sand layers showed that Kumtagh Desert was probably formed as early as 2,097.7±314.7 ka *** the period of 386.9±58.0 ka BP to 285.9±42.9 ka BP,the desert largely expanded and formed its modern distribution *** desert was originally developed in the southwest,subsequently,expanded to the north and *** sedimentary facies of Suosuo gully profile revealed that the desert experienced at least 19 cycles of advance and inverse processes of desertification with an average period of 110 ka in the *** neotectonic movements played an important role in the formation,development and geomorphology of the *** one hand,the movements caused the formation of intermontane fault basin,which was further developed towards the closed drought basin,and caused the formation of natural *** the other hand,under the control of surrounding faults,the unique broom-shaped desert landscape was formed,and the gullies and sand ridges in this region experienced an abrupt directional change from north by west to north by east at the location of 39°45＇-39°55＇*** unique landscape of gravel body that occurred widely in the northern desert was formed after 285.9±42.9 ka *** results in this paper provide the scientific basis for studying the formation age and evolutionary process under the dry climate and

关键词： Kumtagh Desert formation age evolution ancient aeolian sand

深水浅层松散沉积物水合物赋存状态识别与饱和度计算

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天然气地球科学 2024年第10期35卷 1713-1723页

作者：赵军郑超裴健翔汤翟贾将西南石油大学地球科学与技术学院四川成都610500 中海石油(中国)有限公司海南分公司海南海口570311

中国海域深水浅层天然气水合物资源量巨大。海域深水浅层地质疏松,天然气水合物储层无致密盖层、非均质性较强,天然气水合物赋存状态难以识别,极大地制约了天然气水合物饱和度的预测工作。基于海域深水浅层天然气水合物的声、电响应特征... 详细信息

中国海域深水浅层天然气水合物资源量巨大。海域深水浅层地质疏松,天然气水合物储层无致密盖层、非均质性较强,天然气水合物赋存状态难以识别,极大地制约了天然气水合物饱和度的预测工作。基于海域深水浅层天然气水合物的声、电响应特征,利用电阻率和纵波速度交会图版法识别天然气水合物的赋存状态,采用含泥质修正的密度公式计算天然气水合物储层孔隙度。采用含泥质修正的电阻率法、等效介质法和寻找最小联合误差的声电联合反演法预测QDN盆地yl靶区天然气水合物饱和度。预测结果表明,QDN盆地yl靶区采用联合反演法的预测值与氯离子浓度法的实测值最吻合,联合反演法预测误差为0.09%~14.89%,平均误差为6.85%。表明在判断水合物赋存状态的基础上选择相应的声电联合反演饱和度计算模型能极大地提高水合物饱和度的精度,为水合物饱和度的计算提供了一条好的途径。

关键词：水合物饱和度赋存状态识别测井交会图声电联合反演法