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Inhibition of hepatitis B virus via selective apoptosis modulation by Chinese patent medicine Liuweiwuling Tablet

World Journal of Gastroenterology 2024年第13期30卷 1911-1925页

作者： Fei-Lin Ge Yan Yang Lan-Lan Si Yuan-Hua Li Meng-Zhen Cao Jun Wang Zhao-Fang Bai Zhi-Gang Ren xiao-he xiao Yan Liu Department of Chinese Medicine State Key Laboratory of Antiviral DrugsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina The Fifth Medical Center of Chinese PLA General Hospital Beijing 100039China College of Traditional Chinese Medicine Chongqing Medical UniversityChongqing 400010China Beijing Key Laboratory of Emerging Infectious Diseases Peking University Ditan Teaching HospitalBeijing 100015China Department of Infectious Diseases State Key Laboratory of Antiviral Drugsthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina

BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains unclear.AIM To investigate the potential mechanism of action of LWWL against HBV.METHODS In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines.The in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV replication.Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS In hepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,respectively.The inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in hepG2.1403F,hepG2.2.15 and hepG2.A64 cells were 47.78%,39.51%and 46.74%,respectively.Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including hepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,PhepG2.A64(4.89%±1.28%vs 8.52%±0.50%,PhepG2.1403F(3.76%±1.40%vs 7.57%±1.35%,Phere were no significant differences in apoptosis rates between the non-HBV-replicating hepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse m

关键词： hepatitis B virus Chinese patent medicine Antiviral activity Antiviral mechanism Selective apoptosis

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Compatibility with Fructus Ligustri Lucidi Effectively Mitigates Idiosyncratic Liver Injury of Epimedii Folium by Modulating NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 159-170页

作者： xiao-Mei Zhao Zhi-Xin Wu Yan Wang Ying-Jie Xu Ye Xiu Xu Dong Jun-Jie Li Gui-Ji Lv Si-Hao Wang Yu-Rong Li Zhao-Fang Bai xiao-he xiao Department of Pharmacy Chengdu University of Traditional Chinese Medicine Department of hepatology The Fifth Medical Center of PLA General Hospital Department of Military Patient Management The Fifth Medical Center of PLA General Hospital Department of hepatology China Military Institute of Chinese Materia The Fifth Medical Center of PLA General Hospital Department of hepatology National Key Laboratory of Kidney Diseases

Background: Idiosyncratic drug-induced liver injury(IDILI) is a serious side effect of drugs, Epimedii Folium(EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome. Fructus Ligustri Lucidi(FLL), a frequently used medicinal combination with EF, has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity. Aims and Objectives: Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF. Materials and Methods: Western blot was used to determine the expression of related proteins, ELISA was used to detect the secretion of related inflammatory factors IL-1β, IL-18, IL-6 and TNF-α, liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury. Results: Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP, whereas FLL suppressed the NLRP3 inflammasome stimulation. Furthermore, an equal EF to FLL ratio significantly reduced the stimulatory effects of EF. Moreover, EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS. However, when combined with FLL, the detrimental effects of EF were mitigated. Conclusions: FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation. Thus, FLL holds promise for improving the clinical safety profile of EF, shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.

关键词： Epimedii Folium Fructus Ligustri Lucidi idiosyncratic drug-induced liver injury NOD-like receptor family pyrin domain containing 3 inflammasome traditional Chinese medicine

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herb induced liver injury by Xianling Gubao Tablets: A case assessed for causality using updated RUCAM and integrated evidence chain

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Chinese herbal Medicines 2024年第2期16卷 301-309页

作者： Chunyu Li Yingying Li Zhaofang Bai Jiabo Wang Guohui Li xiaohe xiao National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Senior Department of hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China School of Traditional Chinese Medicine Capital Medicinal UniversityBeijing 100069China

Objective:A typical case of Xianling Gubao(XLGB)Tablets-induced liver injury was systematically studied in the clinic and the laboratory.Methods:A patient with herb-induced liver injury(HILI)and a history of taking XLGB Tablets before disease onset was engaged as the study subject,and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method(RUCAM)and the integrated evidence chain(iEC)method recommended by the Guidelines for Diagnosis and Treatment of herb-induced Liver Injury(HILI Guidelines).Results:Clinical history,biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral,alcoholic and autoimmune liver diseases on the diagnosis.Based on an investigation of the patient’s medication history,she was suspected to have HILI caused by XLGB Tablets,as the patient was only taking an oral preparation of XLGB Tablets,and the influence of other drugs on the diagnosis was excluded.This patient with alanine aminotransferase(ALT)3 upper limit of normal(ULN)and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury.The relationship was considered“highly probable”(score of 9)using the updated RUCAM of 2016.Moreover,the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99,suggesting that the patient was consuming XLGB Tablets rather than another drug.LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug,and no chemical additions were found.Examination of the drug for pesticide residues,heavy metals,aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia.Conclusion:In summary,the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC.Therefore,this study provides scientific evidence regarding the causality evaluation o

关键词： chemical analysis compound preparations of traditional chinese medicines integrated evidence chain liver injury Roussel Uclaf Causality Assessment Method Xianling Gubao Tablets

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Experimental distillation of tripartite quantum steering with an optimal local filtering operation

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Photonics Research 2024年第3期12卷 552-562页

作者： QIAN-XI ZHANG xiao-XU FANG he LU School of Physics State Key Laboratory of Crystal MaterialsShandong UniversityJinan 250100China Shenzhen Research Institute of Shandong University Shenzhen 518057China

Multipartite Einstein-Podolsky-Rosen(EPR)steering admits multipartite entanglement in the presence of uncharacterized verifiers,enabling practical applications in semi-device-independent protocols.Such applications generally require stronger steerability,while the unavoidable noise weakens steerability and consequently degrades the performance of quantum information processing.here,we propose the local filtering operation that can maximally distill genuine tripartite EPR steering from N copies of three-qubit generalized Greenberger-Horne-Zeilinger states,in the context of two semi-device-independent scenarios.The optimal filtering operation is determined by the maximization of assemblage fidelity.Analytical and numerical results indicate the advantage of the proposed filtering operation when N is finite and the steerability of initial assemblages is weak.Experimentally,a proof-of-principle demonstration of two-copy distillation is realized with the optical system.The advantage of the optimal local filtering operation is confirmed by the distilled assemblage in terms of higher assemblage fidelity with perfectly genuine tripartite steerable assemblages,as well as the greater violation of the inequality to witness genuine tripartite steerable assemblages.Our results benefit the distillation of multipartite EPR steering in practice,where the number of copies of initial assemblages is generally finite.

关键词： filtering distillation optimal

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Understanding the failure mechanism towards developing high-voltage single-crystal Ni-rich Co-free cathodes

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Green Energy & Environment 2024年第6期9卷 1045-1057页

作者： Jixue Shen Bao Zhang Changwang Hao xiao Li Zhiming xiao Xinyou he Xing Ou Engineering Research Center of the Ministry of Education for Advanced Battery Materials School of Metallurgy and EnvironmentCentral South UniversityChangsha410083China Zhejiang Power New Energy Co. Ltd.Zhuji311899China Material Science and Chemistry Engineering College China University of GeosciencesWuhan430074China

Benefited from its high process feasibility and controllable costs,binary-metal layered structured LiNi_(0.8)Mn_(0.2)O_(2)(NM)can effectively alleviate the cobalt supply crisis under the surge of global electric vehicles(EVs)sales,which is considered as the most promising nextgeneration cathode material for lithium-ion batteries(LIBs).However,the lack of deep understanding on the failure mechanism of NM has seriously hindered its application,especially under the harsh condition of high-voltage without sacrifices of reversible capacity.herein,singlecrystal LiNi_(0.8)Mn_(0.2)O_(2) is selected and compared with traditional LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM),mainly focusing on the failure mechanism of Cofree cathode and illuminating the significant effect of Co element on the Li/Ni antisite defect and dynamic characteristic.Specifically,the presence of high Li/Ni antisite defect in NM cathode easily results in the extremely dramatic H2/H3 phase transition,which exacerbates the distortion of the lattice,mechanical strain changes and exhibits poor electrochemical performance,especially under the high cutoff voltage.Furthermore,the reaction kinetic of NM is impaired due to the absence of Co element,especially at the single-crystal architecture.Whereas,the negative influence of Li/Ni antisite defect is controllable at low current densities,owing to the attenuated polarization.Notably,Co-free NM can exhibit better safety performance than that of NCM cathode.These findings are beneficial for understanding the fundamental reaction mechanism of single-crystal Ni-rich Co-free cathode materials,providing new insights and great encouragements to design and develop the next generation of LIBs with low-cost and high-safety performances.

关键词： Li/Ni antisite defect Dynamic characteristic High-voltage Single-crystal Ni-rich Co-free cathodes Lithium-ion batteries

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TGF-βsignaling in health,disease,and therapeutics

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1466-1505页

作者： Ziqin Deng Tao Fan Chu xiao he Tian Yujia Zheng Chunxiang Li Jie he Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

ransforming growth factor(TGF)-βis a multifunctional cytokine expressed by almost every tissue and cell type.The signal transduction of TGF-βcan stimulate diverse cellular responses and is particularly critical to embryonic development,wound healing,tissue homeostasis,and immune homeostasis in health.The dysfunction of TGF-βcan play key roles in many diseases,and numerous targeted therapies have been developed to rectify its pathogenic activity.In the past decades,a large number of studies on TGF-βsignaling have been carried out,covering a broad spectrum of topics in health,disease,and therapeutics.Thus,a comprehensive overview of TGF-βsignaling is required for a general picture of the studies in this field.In this review,we retrace the research history of TGF-βand introduce the molecular mechanisms regarding its biosynthesis,activation,and signal transduction.We also provide deep insights into the functions of TGF-βsignaling in physiological conditions as well as in pathological processes.TGF-β-targeting therapies which have brought fresh hope to the treatment of relevant diseases are highlighted.Through the summary of previous knowledge and recent updates,this review aims to provide a systematic understanding of TGF-βsignaling and to attract more attention and interest to this research area.

关键词： homeostasis healing wound

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Ultrasound blood flow characteristics changes in fetal umbilical artery thrombosis:A retrospective analysis

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World Journal of Clinical Cases 2024年第2期12卷 240-248页

作者： Si-Jie Hong Li-Wei Hong xiao-Qin he xiao-Hong Zhong Department of Ultrasound Women and Children's HospitalSchool of MedicineXiamen UniversityXiamen 361000Fujian ProvinceChina Ministry of Science and Education Women and Children's HospitalSchool of MedicineXiamen UniversityXiamen 361000Fujian ProvinceChina

BACKGROUND Umbilical artery thrombosis(UAT)is extremely uncommon and leads to adverse perinatal outcomes.Hypercoagulation of blood in pregnant women is suspected to be an important risk for UAT.Ultrasound is an effective way to detect thrombosis.The mother can monitor her own fetal health using ultrasound,which enables her to take preventative action in case of emergency.AIM To investigate ultrasonic blood signal after UAT in the umbilical artery,and evaluate the relationship between hypercoagulability and UAT.METHODS We described a case of a newly formed UAT with markedly altered ultrasonic indices of umbilical artery blood flow,and retrospectively studied it with 18 UAT patients confirmed by histopathology from October 2019 and March 2023 in Xiamen Women and Children's Hospital.Patients’information was collected from medical archives,including maternal clinical data,neonatal outcomes,pathological findings and ultrasonic indices of umbilical artery blood flow,such as systolic-diastolic duration ratio(S/D),resistance index(RI),pulsatility index(PI)and peak systolic velocity(PSV).Ultrasound and coagulation indices were analyzed with matched samples t-test and Wilcoxon rank sum test using the statistical packages in R(version 4.2.1)including car(version 3.1-0)and stats(version 4.2.1),and visualized by ggplot2 package(version 3.3.6).RESULTS A patient with normal findings in second and third-trimester routine ultrasound scan developed UAT with severe changes in ultrasonic indices of umbilical artery blood flow(within 2.5th of reference ranges)in a short period of time.Statistical analysis of umbilical artery blood flow ultrasound indices for 19 patients with UAT showed that the decrease in S/D,RI,and PI and increase of PSV during the disease process was greater than that of non-UAT.All 18 patients delivered in our hospital showed characteristic manifestations of UAT on histological examination after delivery,most of which(16/18)showed umbilical cord abnormalities,with 15 umbilical cord torsion and 1 pseudoknot.Coagul

关键词： Umbilical artery thrombosis Obstetric ultrasonography Peak systolic velocity Hypercoagulation Umbilical cord abnormalities Fetus

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Reactor field reconstruction from sparse and movable sensors using Voronoi tessellation-assisted convolutional neural networks

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Nuclear Science and Techniques 2024年第5期35卷 173-185页

作者： he-Lin Gong Han Li Dunhui xiao Sibo Cheng Paris Elite Institute of Technology Shanghai Jiao Tong UniversityShanghai 200240China School of Mathematical Sciences Tongji UniversityShanghai 200092China Department of Computing Data Science InstituteImperial College LondonLondon SW72AZUK

The aging of operational reactors leads to increased mechanical vibrations in the reactor interior.The vibration of the incore sensors near their nominal locations is a new problem for neutronic field reconstruction.Current field-reconstruction methods fail to handle spatially moving sensors.In this study,we propose a Voronoi tessellation technique in combination with convolutional neural networks to handle this challenge.Observations from movable in-core sensors were projected onto the same global field structure using Voronoi tessellation,holding the magnitude and location information of the sensors.General convolutional neural networks were used to learn maps from observations to the global field.The proposed method reconstructed multi-physics fields(including fast flux,thermal flux,and power rate)using observations from a single field(such as thermal flux).Numerical tests based on the IAEA benchmark demonstrated the potential of the proposed method in practical engineering applications,particularly within an amplitude of 5 cm around the nominal locations,which led to average relative errors below 5% and 10% in the L_(2) and L_(∞)norms,respectively.

关键词： Voronoi tessellation Field reconstruction Nuclear reactors Reactor physics On-line monitoring

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An improved algorithm for retrieving thin sea ice thickness in the Arctic Ocean from SMOS and SMAP L-band radiometer data

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Acta Oceanologica Sinica 2024年第3期43卷 127-138页

作者： Lian he Senwen Huang Fengming Hui xiao Cheng School of Geospatial Engineering and Science Sun Yat-Sen Universityand Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)Zhuhai 519082China Key Laboratory of Comprehensive Observation of Polar Environment(Sun Yat-Sen University) Ministry of EducationZhuhai 519082China

The aim of this study was to develop an improved thin sea ice thickness(SIT)retrieval algorithm in the Arctic Ocean from the Soil Moisture Ocean Salinity and Soil Moisture Active Passive L-band radiometer data.This SIT retrieval algorithm was trained using the simulated SIT from the cumulative freezing degree days model during the freeze-up period over five carefully selected regions in the Beaufort,Chukchi,East Siberian,Laptev and Kara seas and utilized the microwave polarization ratio(PR)at incidence angle of 40°.The improvements of the proposed retrieval algorithm include the correction for the sea ice concentration impact,reliable reference SIT data over different representative regions of the Arctic Ocean and the utilization of microwave polarization ratio that is independent of ice temperature.The relationship between the SIT and PR was found to be almost stable across the five selected regions.The SIT retrievals were then compared to other two existing algorithms(i.e.,UH_SIT from the University of Hamburg and UB_SIT from the University of Bremen)and validated against independent SIT data obtained from moored upward looking sonars(ULS)and airborne electromagnetic(EM)induction sensors.The results suggest that the proposed algorithm could achieve comparable accuracies to UH_SIT and UB_SIT with root mean square error(RMSE)being about 0.20 m when validating using ULS SIT data and outperformed the UH_SIT and UB_SIT with RMSE being about 0.21 m when validatng using EM SIT data.The proposed algorithm can be used for thin sea ice thickness(he Arctic Ocean and requires less auxiliary data in the SIT retrieval procedure which makes its implementation more practical.

关键词： Arctic sea ice sea ice thickness remote sensing Soil Moisture Active Passive(SMAP) Soil Moisture Ocean Salinity and Soil(SMOS)

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Risk factors for cognitive impairment in patients with chronic kidney disease

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World Journal of Psychiatry 2024年第2期14卷 308-314页

作者： xiao-Hui Wang Yong he Huan Zhou Ting xiao Ran Du Xin Zhang Department of Nephrology The Fifth Hospital of WuhanWuhan 430050Hubei ProvinceChina Department of Nephrology The Central Hospital of Enshi Tujia and Miao Autonomous PrefectureEnshi 445000Hubei ProvinceChina

BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.

关键词： Cognitive impairment Cognitive dysfunction Chronic kidney disease

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