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Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn’s disease patients

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World Journal of Gastroenterology 2019年第38期25卷 5850-5861页

作者： Xia Zhu Kang Chao Miao Li Wen Xie Hong Zheng Jin-Xin Zhang Pin-Jin Hu Min Huang Xiang Gao Xue-Ding Wang institute of Clinical Pharmacology School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510000Guangdong ProvinceChina Department of Gastroenterology the Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510000Guangdong ProvinceChina Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261United States School of Public Health Sun Yat-sen UniversityGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.

关键词： Crohn’s disease Thioguanine nucleotide levels Nucleoside diphosphatelinked moiety X-type motif 15 Thiopurine-induced leukopenia

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The therapeutic efficacy of the Shenqi Fuzheng injection for treating chronic heart failure: A systematic review and meta-analysis

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South China Journal of Cardiology 2022年第3期23卷 191-204页

作者：王川杨夏雯姚东风刘维海 XU Xin-ya 史永恒刘继平朱平闫海钊 Department of Pharmacology Shanxi University of Chinese MedicineXianyang 712000China Guangdong Cardiovascular institute Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhou 510100China Affiliated Hospital of Shaanxi University of Chinese Medicine Xianyang 712000China Key Laboratory of Regenerative Biology South China Institute for Stem CellBiology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China

Chronic heart failure(CHF) is a cardiovascular disease which is hard to treat and which threatens public health. It is imperative to seek a new treatment for CHF. The Shenqi Fuzheng compound injection(SQFZI) is often used in China for treating patients with this condition. We used a meta-analysis to evaluate the therapeutic efficacy of SQFZI combined with conventional therapy for the treatment of chronic heart failure. Researchers searched the databases for randomized controlled trials(RCTs) of SQFZI combined with conventional therapy for treating CHF. There were no language or regional restrictions. Quality assessment was conducted according to the Cochrane Handbook, and data analysis was carried out using RevMan 5.3 software. Fifteen RCTs were selected, which included 1198 patients. Using meta-analysis, we found that the clinical efficacy of the experimental group(SQFZI combined with conventional therapy) was better than the control group(conventional therapy alone). Additionally,SQFZI combined with conventional therapy improved left ventricular ejection fraction, left ventricular end-diastolic dimension, cardiac output, stroke volume, brain natriuretic peptide, N-terminal pro-brain natriuretic peptide, and other cardiac indexes. Two trials reported non-serious adverse events, the others reported no adverse events. Based on this meta-analysis, we suggest that SQFZI combined with conventional therapy can effectively improve the efficacy of treatment for CHF patients. However, due to insufficient evidence regarding its safety, more trials of SQFZI for treating CHF are needed.

关键词： Shenqi Fuzheng injection chronic heart failure meta-analysis systematic review

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Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy

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Acta Pharmaceutica Sinica B 2019年第4期9卷 843-857页

作者： Caifang Gao Jianming Liang Ying Zhu Chengli Ling Zhekang Cheng Ruixiang Li Jing Qin Weigen Lu Jianxin Wang Department of Pharmaceutics School of PharmacyFudan University&Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai 201203China Shanghai institute of Pharmaceutical Industry China State Institute of Pharmaceutical IndustryShanghai 201203China guangzhou University of Chinese Medicine Guangzhou 510006China School of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China School of Pharmacy Minzu University of ChinaBeijing 100081China

Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood–brain barrier(BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers.Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and gliomatargeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs.The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of mentholmodified casein nanoparticles(M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-MCA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining ofthe organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.

关键词： Glioma Casein Menthol Nanoparticles Brain targeting Blood–brain barrier 10-Hydroxycamptothecin

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Internal Waves Generated by Tidal Flows over a Triangular Ridge with Critical Slopes

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Journal of Ocean University of China 2019年第5期18卷 1005-1012页

作者： NIE Yuhua CHEN Zhiwu XIE Jieshuo XU Jiexin HE Yinghui CAI Shuqun South China Sea Information Center of State Oceanic Administration Guangzhou 510310China State Key Laboratory of Tropical Oceanography South China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China University of Chinese Academy of Sciences Beijing 100049China Institution of South China Sea Ecology and Environmental Engineering Chinese Academy of SciencesGuangzhou 510301China

Direct numerical simulations are performed to investigate the generation of internal waves by tide-topography interaction in a lab-scale model.The bottom topography is a triangular ridge with two critical slopes.With increasing tidal forcing,subharmonic instabilities are identified,which cause internal wave beams to become unstable and turbulent.Kinetic energy densities in the upward going beams from the ridge top are stronger than those from the ridge bottom,whereas the reverse is true for the energy flux.This disparity between energy and energy flux is due to the existence of strong pressure disturbances near the ridge bottom.On each side of the critical ridge,there exists an amphidromic point,from which internal wave beams are emitted in opposite directions.The calculated energy conversion rate scales linearly with the square of the forcing amplitude and agrees within 13%of theoretical prediction,even when turbulence occurs.The fraction of radiated baroclinic energy becomes saturated in the range of low excursion parameter considered,which agrees with the behavior in large-scale systems wherein mixing parameterizations must be used.The present work enriches the studies on the generation of internal waves over a critical triangular ridge.

关键词： Internal wave beam parametric subharmonic instability internal wave energetics tide-topography interaction

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Dynamic Spectrum Anti-Jamming with Distributed Learning and Transfer Learning

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China Communications 2023年第12期20卷 52-65页

作者： Xinyu Zhu Yang Huang Delong Liu Qihui Wu Xiaohu Ge Yuan Liu Key Laboratory of Dynamic Cognitive System of Electromagnetic Spectrum Space Ministry of Industry and Information TechnologyNanjing University of Aeronautics and AstronauticsNanjing 210016China The 723 institute of CSSC Yangzhou 225001China School of Electronic Information and Communications Huazhong University of Science and TechnologyWuhan 430074China School of Electronic and Information Engineering South China University of TechnologyGuangzhou 510641China

Physical-layer security issues in wireless systems have attracted great attention.In this paper,we investigate the spectrum anti-jamming(AJ)problem for data transmissions between devices.Considering fast-changing physical-layer jamming attacks in the time/frequency domain,frequency resources have to be configured for devices in advance with unknown jamming patterns(i.***.the time-frequency distribution of the jamming signals)to avoid jamming signals emitted by malicious devices.This process can be formulated as a Markov decision process and solved by reinforcement learning(RL).Unfortunately,stateof-the-art RL methods may put pressure on the system which has limited computing resources.As a result,we propose a novel RL,by integrating the asynchronous advantage actor-critic(A3C)approach with the kernel method to learn a flexible frequency pre-configuration policy.Moreover,in the presence of time-varying jamming patterns,the traditional AJ strategy can not adapt to the dynamic interference strategy.To handle this issue,we design a kernelbased feature transfer learning method to adjust the structure of the policy function online.Simulation results reveal that our proposed approach can significantly outperform various baselines,in terms of the average normalized throughput and the convergence speed of policy learning.

关键词： A3C anti-jamming reinforcement learning spectrum transfer learning wireless system

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Generation　of　Stable　Near－infrared　and　Violet　Femtosecond　Pulses　from　a　Self－mode－locked　Ti：Sapphire　Laser

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Chinese Journal of Lasers 1995年第4期4卷 347-354页

作者： LI Weiliang QIU Zhiren PENG Wenji ZENG Xueran YU Zhenxin(institute for Laser and Spectroscopy,Zhongshan University,guangzhou 510275, China) Zhongshan Univ Guangzhou China

ＧｅｎｅｒａｔｉｏｎｏｆＳｔａｂｌｅＮｅａｒ－ｉｎｆｒａｒｅｄａｎｄＶｉｏｌｅｔＦｅｍｔｏｓｅｃｏｎｄＰｕｌｓｅｓｆｒｏｍａＳｅｌｆ－ｍｏｄｅ－ｌｏｃｋｅｄＴｉ：ＳａｐｐｈｉｒｅＬａｓｅｒ￥ＬＩＷｅｉｌｉａｎｇ；ＱＩ... 详细信息

ＧｅｎｅｒａｔｉｏｎｏｆＳｔａｂｌｅＮｅａｒ－ｉｎｆｒａｒｅｄａｎｄＶｉｏｌｅｔＦｅｍｔｏｓｅｃｏｎｄＰｕｌｓｅｓｆｒｏｍａＳｅｌｆ－ｍｏｄｅ－ｌｏｃｋｅｄＴｉ：ＳａｐｐｈｉｒｅＬａｓｅｒ￥ＬＩＷｅｉｌｉａｎｇ；ＱＩＵＺｈｉｒｅｎ；ＰＥＮＧＷｅｎｊｉ...

关键词： self-mode-locked Ti:Sapphire laser femtosecond pulse

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In vitro antioxidant activities of selected seaweeds from Southeast coast of India

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Asian Pacific Journal of Tropical Medicine 2011年第3期4卷 205-211页

作者： Gopalraj Karthikai Devi Karunamoorthy Manivannan Ganapathy Thirumaran Fatimson Arockiya Aarthi Rajathi Perumal Anantharaman Centre of Advanced Study in Marine Biology Faculty of Marine SciencesAnnamalai UniversityParangipettai-608502Tamil NaduIndia institute of Hydrobiology Jinan UniversityGuangzhou-510638China

Objective:In vitro antioxidant activities of three selected Indian seaweeds viz.,Halimeda tuna(H.tuna),Turbinaria conoides(T.conoides) and Gracilaria foliifera(G.foliifera) were evaluated.Methods:Total antioxidant activity,total phenolic content,and reducing power of crude methanol and diethyl ether extracts were determined.Results:Total phenolic content and total antioxidant activity were higher(1.231±0.173 mg GAE/g,1.675±0.361 mg GAE/g) in T.conoides respectively.Reducing power of crude methanol extract increased with concentrations of the extract.The Fourier transform-infra red spectrum analysis revealed the presence of polyphenolic signals.The seaweed extracts displayed moderate antioxidant activity compared to gallic acid standard.Conclusions:The seaweeds could be considered for curing diseases from oxidative deteriorations.

关键词： FT-IR Reducing power Seaweeds Total phenolic content Total antioxidant activity

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METTL5 regulates cranial suture fusion via Wnt signaling

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Fundamental Research 2023年第3期3卷 369-376页

作者： Kexin Lei Ruoshi Xu Qian Wang Qiuchan Xiong Xinyi Zhou Qiwen Li Dutmanee Seriwatanachai Shuibin Lin Chenchen Zhou Quan Yuan State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Department of Oral Biology Faculty of DentistryMahidol UniversityBangkok 73170Thailand Center for Translational Medicine Precision Medicine InstituteThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China

METTL5 is a methyltransferase that mediates eukaryotic 18S ribosomal RNA m^(6)A modification,and its mutations lead to intellectual disability,microcephaly,and facial dysmorphism in patients.However,the role of METTL5 in craniofacial development remains poorly understood.This study demonstrates that Mettl5 knockout mice exhibit poor ossification,widened cranial sutures,and a cleidocranial dysplasia-like phenotype.Deletion of Mettl5 leads to increased proliferation and decreased osteogenic differentiation of suture mesenchymal stem cells.Mechanistically,we find that Wnt signaling is significantly downregulated after Mettl5 knockout.Overall,we reveal an essential role of METTL5 in craniofacial development and osteogenic differentiation of suture mesenchymal stem cells,making METTL5 a potential diagnostic and therapeutic target for craniofacial developmental diseases.

关键词： METTL5 N6-methyladenosine Cranial suture Osteogenic differentiation Mesenchymal stem cells

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Background Characteristics of Atmospheric CO2 and the Potential Source Regions in the Pearl River Delta Region of China

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Advances in Atmospheric Sciences 2020年第6期37卷 557-568页

作者： Boru MAI Xuejiao DENG Fang ZHANG Hao HE Tian LUAN Fei LI Xia LIU institute of Tropical and Marine Meteorology China Meteorological AdministrationGuangzhou 510640China College of Global Change and Earth System Science Beijing Normal UniversityBeijing 100875China Department of Atmospheric and Oceanic Science University of MarylandCollege ParkMD 20742USA Chinese Academy of Meteorological Sciences Beijing 100081China guangzhou Meteorological Observatory Guangzhou 511430China

Mole fractions of atmospheric CO2(XCO2)have been continuously measured from October 2014 to March 2016 at the guangzhou Panyu Atmospheric Composition Site(23.00°N,113.21°E;140 m MSL)in the Pearl River Delta(PRD)region using a cavity ring-down spectrometer.Approximately 66.63%,19.28%,and 14.09%of the observed values were filtered as background,pollutant source,and sink due to biospheric uptake,respectively,by applying a robust local regression procedure.Their corresponding mean values were 424.12±10.12 ppm(×10-6 mol mol-1),447.83±13.63 ppm,and 408.83±7.75 ppm.The background XCO2 levels were highest in spring and winter,moderate in autumn,and lowest in summer.The diurnal XCO2 was at a minimum from 1400-1600 LST(Local Standard Time)and a maximum at 0500 LST the next day.The increase of XCO2 in spring and summer was mainly associated with polluted air masses from south coastal Vietnam,the South China Sea,and the southeast Pearl River Estuary.With the exception of summer,airflow primarily from marine regions southeast of Taiwan that passed over the Pearl River Estuary had a greater impact on XCO2,suggesting an important potential source region.

关键词： Pearl southeast Delta

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Recent progresses on designing and manufacturing of bulk refractory alloys with high performances based on controlling interfaces

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Journal of Materials Science & Technology 2020年第17期52卷 29-62页

作者： T.Zhang H.W.Deng Z.M.Xie R.Liu J.F.Yang C.S.Liu X.P.Wang Q.F.Fang Y.Xiong School of Physics and Electronic Engineering Guangzhou UniversityGuangZhou 510006China Key Laboratory of Materials Physics Institute of Solid State PhysicsChinese Academy of SciencesHefei 230031China State Key Laboratory of Environment Friendly Energy Materials West South University of Sciences and TechnologyMianYang 621010China

Refractory alloys such as tungsten and molybdenum based alloys with high strength,thermal/electrical conductivity,low coefficient of thermal expansion and excellent creep resistances are highly desirable for applications in nuclear facilities,critical components in aerospace and defense components.However,the serious embrittlement limits the engineering usability of some refractory alloys.A lot of research results indicate that the performances of refractory alloys are closely related to the physical/chemical status,such as the interface dimension,interface type,interface composition of their grain boundaries(GBs),phase boundaries(PBs)and other interface features.This paper reviewed the recent progress of simulations and experiments on interface design strategies that achieve high performance refractory alloys.These strategies include GB interface purifying/strengthening,PB interface strengthening and PB/GB synergistic strengthening.Great details are provided on the design/fabrication strategy such as GB interface controlling,PB interface controlling and synergistic control of multi-scaled interfaces.The corresponding performances such as the mechanical property,thermal conductivity,thermal load resistance,thermal stability,irradiation resistance,and oxidation resistance are reviewed in the aspect to the effect of interfaces.In addition,the relationships between these interfaces and material properties are discussed.Finally,future developments and potential new research directions for refractory alloys are proposed.

关键词： Interface controlling Designing and manufacturing Refractory alloys Structure and performance

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