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Liver Research 2018年第4期2卷 186-199页

作者： helen h.wang Piero Portincasa Min Liu Patrick Tso david q.-h.wang Department of Medicine Division of Gastroenterology and Liver DiseasesMarion Bessin Liver Research CenterAlbert Einstein College of MedicineBronxNYUSA Department of Biomedical Sciences and human Oncology Clinica Medica“A.Murri”University of Bari“Aldo Moro”Medical SchoolBariItaly Department of Pathology and Laboratory Medicine University of Cincinnati College of MedicineCincinnatiOHUSA

The terms biliary sludge and cholesterol microlithiasis(hereafter referred to as microlithiasis)were originated from different diagnostic techniq.es and may represent different stages of cholesterol gall-stone disease.Although the pathogenesis of biliary sludge and microlithiasis may be similar,micro-lithiasis could be preceded by biliary sludge,followed by persistent precipitation and aggregation of solid cholesterol crystals,and eventually,gallstone formation.Many clinical conditions are clearly associated with the formation of biliary sludge and microlithiasis,including total parenteral nutrition,rapid weight loss,pregnancy,organ transplantation,administration of certain medications,and a variety of acute and chronic illnesses.Numerous studies have demonstrated complete resolution of biliary sludge in approximately 40%of patients,a cyclic pattern of disappearing and reappearing in about 40%,and progression to gallstones in nearly 20%.Although only a minority of patients with ultrasonographic demonstration of biliary sludge develop gallstones,it is still a matter of controversy whether micro-lithiasis could eventually evolve to cholesterol gallstones.Biliary sludge and microlithiasis are asymp-tomatic in the vast majority of patients;however,they can cause biliary colic,acute cholecystitis,and acute pancreatitis.Biliary sludge and microlithiasis are most often diagnosed ultrasonographically and bile microscopy is considered the gold standard for their diagnosis.Specific measures to prevent the development of biliary sludge are not practical or cost-effective in the general population.Laparoscopic cholecystectomy offers the most definitive therapy on biliary sludge.Endoscopic sphincterotomy or surgical intervention is effective for microlithiasis-induced pancreatitis.Ursodeoxycholic acid can effectively prevent the recurrence of solid cholesterol crystals and significantly reduce the risk of recurrent pancreatitis.

关键词： Biliary sludge Cholesterol microlithiasis Acute cholecystitis Acute pancreatitis Biliary colic Cholesterol monohydrate crystals Lithogenic bile

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New insights into the role of Lith genes in the formation of cholesterol-supersaturated bile

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Liver Research 2017年第1期1卷 42-53页

作者： helen h.wang Tiangang Li Piero Portincasa david A.Ford Brent A.Neuschwander-Tetri Patrick Tso david q.h.wang Department of Internal Medicine Division of Gastroenterology and HepatologySaint Louis University School of MedicineSt.LouisMOUSA Department of Pharmacology Toxicology and TherapeuticsKansas University Medical CenterKansas CityKSUSA Clinica Medica“A.Murri” Department of Biomedical Sciences and Human OncologyUniversity of Bari“Aldo Moro”Medical SchoolBariItaly Department of Biochemistry and Molecular Biology Saint Louis University School of MedicineSt.LouisMOUSA Department of Pathology and Laboratory Medicine University of Cincinnati College of MedicineCincinnatiOHUSA

Cholesterol gallstone formation represents a failure of biliary cholesterol homeostasis in which the physical-chemical balance of cholesterol solubility in bile is disturbed.Lithogenic bile is mainly caused by persistent hepatic hypersecretion of biliary cholesterol and sustained cholesterol-supersaturated bile is an essential prereq.isite for the precipitation of solid cholesterol monohydrate crystals and the formation of cholesterol gallstones.The metabolic determinants of the supply of hepatic cholesterol molecules that are recruited for biliary secretion are dependent upon the input-output balance of cholesterol and its catabolism in the liver.The sources of cholesterol for hepatic secretion into bile have been extensively investigated;however,to what extent each cholesterol source contributes to hepatic secretion is still unclear both under normal physiological conditions and in the lithogenic state.Although it has been long known that biliary lithogenicity is initiated by hepatic cholesterol hypersecretion,the genetic mechanisms that cause supersaturated bile have not been defined yet.Identification of the Lith genes that determine hepatic cholesterol hypersecretion should provide novel insights into the primary genetic and pathophysiological defects for gallstone formation.In this review article,we focus mainly on the pathogenesis of the formation of supersaturated bile and gallstones from the viewpoint of genetics and pathophysiology.A better understanding of the molecular genetics and pathophysiology of the formation of cholesterol-supersaturated bile will undoubtedly facilitate the development of novel,effective,and noninvasive therapies for patients with gallstones,which would reduce the morbidity,mortality,and costs of health care associated with gallstones,a very prevalent liver disease worldwide.

关键词： Bile flow Bile acid Biliary secretion Lith gene Micelle Vesicle

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The mechanism of dysbiosis in alcoholic liver disease leading to liver cancer

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hepatoma Research 2020年第2期6卷 20-32页

作者： Nahum Méndez-Sánchez Alejandro Valencia-Rodríguez Alfonso Vera-Barajas Ludovico Abenavoli Emidio Scarpellini Guadalupe Ponciano-Rodríguez david q.-h.wang Liver Research Unit Medica Sur Clinic&FoundationMexico City 14050Mexico Faculty of Medicine National Autonomous University of MexicoMexico City 04510Mexico Department of health Sciences University“Magna Graecia”Viale EuropaCatanzaro 88100Italy Clinical Nutrition Unit and Internal Medicine Unit“Madonna del Soccorso”General HospitalVia Luciano Manara 7San Benedetto del Tronto(AP)63074Italy Public health Department Faculty of MedicineNational Autonomous University of MexicoMexico City 04510Mexico Department of Medicine and Genetics Division of Gastroenterology and Liver DiseasesMarion Bessin Liver Research CenterEinstein-Mount Sinai Diabetes Research CenterAlbert Einstein College of MedicineBronxNY 10461USA

Currently, alcoholic liver disease (ALD) is one of the most prevalent chronic liver diseases worldwide, representing one of the main etiologies of cirrhosis and hepatocellular carcinoma (hCC). Although we do not know the exact mechanisms by which only a selected group of patients with ALD progress to the final stage of hCC, the role of the gut microbiota within the progression to hCC has been intensively studied in recent years. To date, we know that alcohol-induced gut dysbiosis is an important feature of ALD with important repercussions on the severity of this disease. In essence, an increased metabolism of ethanol in the gut induced by an excessive alcohol consumption promotes gut dysfunction and bacterial overgrowth, setting a leaky gut. This causes the translocation of bacteria, endotoxins, and ethanol metabolites across the enterohepatic circulation reaching the liver, where the recognition of the pathogen-associated molecular patterns via specific Toll-like receptors of liver cells will induce the activation of the nuclear factor kappa-B pathway, which releases pro-inflammatory cytokines and chemokines. In addition, the mitogenic activity of hepatocytes will be promoted and cellular apoptosis will be inhibited, resulting in the development of hCC. In this context, it is not surprising that microbiota-regulating drugs have proven effectiveness in prolonging the overall survival of patients with hCC, making attractive the implementation of these drugs as co-adjuvant for hCC treatment.

关键词： Alcoholic liver disease gut microbiota dysbiosis hepatocellular carcinoma

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Clinical correlation between TNFRSF12A and hepatocellular carcinoma and its effect on immunoregulation of tumor cells

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Fudan University Journal of Medical Sciences 2024年第3期51卷 368-377页

作者： Zhu J. Fang P.-q. Pan B.-S. Guo W. wang B.-L. Department of Laboratory Medicine Zhongshan Hospital Fudan University Shanghai 200032 China Department of Laboratory Medicine Zhongshan Hospital（Xiamen Branch） Fudan University Fujian Province Xiamen 361015 China Department of Laboratory Medicine Baoshan Wusong Central Hospital Shanghai 200940 China Department of Laboratory Medicine Shanghai Geriatric Medical Center Shanghai 201104 China

Objective To investigate the role of the TNFRSF12A molecule in the pathogenesis of liver cancer. Methods Through comprehensive analysis of the Cancer Genome Atlas Program（TCGA）database and single-cell seq.encing data，we studied the expression of TNFRSF12A in liver cancer and its correlation with prognosis. hPA database was utilized to analyze the subcellular localization of TNFRSF12A，and GO and KEGG analyses were performed by david. TIME 2.0 was employed to analyze the correlation between TNFRSF12A and immune cell infiltration in liver cancer tissues. Results TNFRSF12A was found to be highly expressed in liver cancer tissues，significantly correlating with patient survival prognosis（OS：hR=1.61，P=0.007 0；RFS：hR=1.45，P=0.037 0；PFS：hR=1.30，P=0.099 0；DSS：hR=1.67，P=0.027 0），as well as age（P=0.046 7）and BCLC stage（P=0.045 6）. TNFRSF12A co-expressed with tumor stem cell markers（CD24，SOX4，ANPEP），indicating a strong link to malignancy. Furthermore，molecular functional analysis unveiled that IL-2R primarily existed in the cell cytoplasm and played a role in processes such as cell apoptosis，invasion，and protein binding. Moreover，TNFRSF12A was associated with Treg cells and immune cell infiltration，further suggesting its role in tumor immune regulation. Conclusion TNFRSF12A exhibits a significant elevation within liver tumors and shows a notable correlation with patients’prognosis. Tumor cells engage in interactions with cytokines produced by Tregs，thereby reshaping the tumor microenvironment. The potential clinical significance of TNFRSF12A as a prognostic marker for tumors holds promise in offering novel avenues for personalized treatment and prognosis prediction. © 2024 Fudan University. All rights reserved.

关键词： hepatocellular carcinoma immune cell infiltration stemness marker TNFRSF12A

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q.antification of perfluorinated compounds in atmospheric particulate shows potential connection with environmental event

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Journal of Environmental Sciences 2024年第2期136卷 237-247页

作者： hua Tang Ying wang Shengling Si hongli Li david Da Yong Chen National Institute of Metrology 18 BeisanhuandongluChaoyang DistrictBeijing 100029China School of Chemistry and Materials Science Nanjing Normal UniversityNanjing 210023China Si Chuan Zhong Ce Biao Wu Technology Co.Ltd. Sichuan 610052China Department of Chemistry University of British ColumbiaVancouver V6T 1Z1BCCanada

A method of q.antification of perfluorinated compounds(PFCs)from atmospheric particulate matter(APM)is described.A single step pretreatment method,selective pressurized liq.id extraction(SPLE),was developed to reduce the high matrix background and avoid contamination from commonly used multiple sample pretreatment steps.An effective sorbent was selected to purify the PFCs during SPLE,followed by liq.id chromatography-tandem mass spectrometry(LC–MS/MS),for q.antification of PFCs.Conditions affecting the SPLE efficiency,including temperature,static extraction time,and number of extraction cycles used,were studied.The optimum conditions were found to be 120℃,10 min,and 3 cycles,respectively.LC-MS/MS method was developed to obtain the optimal sensitivity specific to PFCs.The method detection limits(MDLs)were 0.006 to 0.48 ng/g for the PFCs studied and the linear response range was from 0.1 to 100 ng/g.To ensure accurate values were obtained,each step of the experiment was evaluated and controlled to prevent contamination.The optimized method was tested by performing spiking experiments in natural particulate matter matrices and good rates of recovery and reproducibility were obtained for all target compounds.Finally,the method was successfully used to measure 16 PFCs in the APM samples collected in Beijing over five years from 2015 to 2019.It is observed that some PFCs follow the trend of total PFC changes,and can be attributed to the environment influencing events and policy enforcement,while others don't seem to change as much with time of the year or from year to year.

关键词： Selective pressurized liq.id extraction Liq.id chromatography-mass spectrometry Perfluorinated compounds Atmospheric particulate matter Pollution control

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Uncovering the dominant contribution of intermediate volatility compounds in secondary organic aerosol formation from biomass-burning emissions

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National Science Review 2024年第3期11卷 150-158页

作者： Kun Li Jun Zhang david M.Bell Tiantian wang houssni Lamkaddam Tianq. Cui Lu q. Mihnea Surdu Dongyu wang Lin Du Imad El haddad Jay G.Slowik Andre S.h.Prevot Environment Research Institute Shandong University Laboratory of Atmospheric Chemistry Paul Scherrer Institute

Organic vapors from biomass burning are a major source of secondary organic aerosols(SOAs). Previous smog chamber studies found that the SOA contributors in biomass-burning emissions are mainly volatile organic compounds(VOCs). While intermediate volatility organic compounds(IVOCs) are efficient SOA precursors and contribute a considerable fraction of biomass-burning emissions, their contribution to SOA formation has not been directly observed. here, by deploying a newly-developed oxidation flow reactor to study SOA formation from wood burning, we find that IVOCs can contribute ～70% of the formed SOA, i.e.>2 times more than VOCs. This previously missing SOA fraction is interpreted to be due to the high wall losses of semi-volatile oxidation products of IVOCs in smog chambers. The finding in this study reveals that SOA production from biomass burning is much higher than previously thought, and highlights the urgent need for more research on the IVOCs from biomass burning and potentially other emission sources.

关键词： atmospheric chemistry biomass burning secondary organic aerosol intermediate volatility organic compounds

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Repeatability and reproducibility of corneal higher-order aberrations measurements after small incision lenticule extraction using the Scheimpfug-Placido topographer

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Eye and Vision 2024年第1期10卷 1-9页

作者： Rui Ning Rongrong Gao david PPiñero Jun Zhang q.ngyi Gao Yili Jin Yiran wang Chenxiao wang Jinhai huang Eye hospital and School of Ophthalmology and Optometry Wenzhou Medical UniversityWenzhouZhejiangChina Eye Institute and Department of Ophthalmology Eye and ENT HospitalFudan UniversityShanghaiChina Group of Optics and Visual Perception Department of OpticsPharmacology and AnatomyUniversity of AlicanteAlicanteSpain NhC Key Laboratory of Myopia(Fudan University) Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghaiChina Shanghai Research Center of Ophthalmology and Optometry ShanghaiChina

Background:To evaluate the precision of corneal higher-order aberrations measurements after small incision lenticule extraction(SMILE)using the Sirius Scheimpfug-Placido topographer(CSO,Italy).Methods:Seventy-fve eyes from 75 postoperative subjects were included in this prospective study.Three consecutive corneal aberrometric measurements were obtained with the Scheimpfug-Placido topographer by two experienced operators to assess intra-and inter-observer reproducibility.The within-subject standard deviation(Sw),test-retest repeatability(TRT)and the intraclass correlation coefcient(ICC)were calculated.Results:For intraobserver repeatability of anterior and total corneal aberrations,all ICCs were more than 0.922,except for trefoil(0.722 to 0.768).The ICCs of total root mean sq.are(RMS),coma Z(3,±1),and spherical aberration Z(4,0)were over 0.810 while higher-order RMS,trefoil Z(3,±3),and astigmatism II Z(4,±2)were below 0.634 for posterior corneal surface aberrations.All Sw values for all types of aberrations were eq.al to or below 0.07μm.Regarding interobserver reproducibility,all TRT values were no more than 0.12μm,0.05μm,and 0.11μm for anterior,posterior,and total corneal aberrations,respectively.The ICC values ranged from 0.875 to 0.989,from 0.686 to 0.976 and over 0.834 for anterior,posterior,and total corneal aberrations,respectively.Conclusions:The repeatability of measurements of anterior and total corneal aberrations with the Sirius system in corneas after SMILE surgery was high,except for trefoil.There was some variability in posterior corneal aberrometric measurements.high reproducibility of corneal aberrometric measurements was observed between measurements of both examiners,except for trefoil,with poor to moderate reproducibility.

关键词： Sirius higher-order aberrations Repeatability Reproducibility Small incision lenticule extraction

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hepatitis B virus genotypes in precision medicine of hepatitis Brelated hepatocellular carcinoma:Where we are now

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1097-1103页

作者： Caecilia h C Sukowati Sri Jayanti Turyadi Turyadi david h Muljono Claudio Tiribelli Eijkman Research Center for Molecular Biology Research Organization for HealthNational Research and Innovation Agency of IndonesiaJakarta 10340Indonesia Liver Cancer Unit Fondazione Italiana Fegato ONLUSTrieste 34149Italy Faculty of Medicine Hasanuddin UniversityMakassar 90245South SulawesiIndonesia Faculty of Medicine and health University of SydneySydney 2050Australia

hepatitis B virus(hBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(hCC).hBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for hBV-related hCC and the success of therapeutical approaches against hCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of hBV genetic diversity is still valid in terms of viral oncogenicity to the hCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.

关键词： hepatitis B virus hepatocellular carcinoma Genotypes Pathogenesis Precision medicine

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A combined experimental and DEM investigation of grain interlocking in sheared granular assemblies

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Particuology 2024年第7期90卷 436-451页

作者： Rui Lu q.ang Luo Tengfei wang david P.Connolly Tao Xie School of Civil Engineering Southwest Jiaotong UniversityChengdu 610031China Key Laboratory of high-Speed Railway Engineering(Southwest Jiaotong University) Ministry of EducationChengdu 610031China School of Civil Engineering University of LeedsLeeds LS29JTUK Department of Civil Engineering McMaster UniversityHamiltonONCanada

Compacted granular material,integral to geotechnical engineering,undergoes translation,rotation,and interlocking when subject to shear displacements or external loads.The present study focuses on the interlocking of heterogeneous granular materials,a complex behavior influenced by gradation,compaction,and varying particle geometry,and has conseq.ently received limited attention in existing research.To address this research gap,we conducted an analysis on the effect of grain interlocking on the shear resistance of granular assemblies,using a combination of laboratory testing and the discrete element method(DEM).Initially,large-scale direct shear tests were conducted on gravel−sand mixes with varying degrees of compaction and normal pressure.One of the mixes also underwent subseq.ent shear reversal to explore the differences in grain interlocking between the two shearing processes on the shear plane.After analyzing the laboratory results,a mesoscopic scale investigation was performed by replicating the test using discrete element simulations.To facilitate this,granular particle geometries were measured using 3D laser scanning based on the physical lab tests.Subseq.ently,based on these scans,discrete element R-block and ball models were utilized to construct both the coarse and fine particles within the mix.Surface vibro-compaction was employed to regulate the degree of compaction.The results indicate that an increase in vertical pressure,coupled with a zero dilatancy angle,results in a rising stress ratio,indicative of grain interlocking.This interlocking exhibits a positive correlation with both the coarse content and the degree of compaction,and varies depending on the shear displacement.As interlocking progresses,the shear band,induced by particle movement,expands and is associated with reduced particle rotation near the shear band.The study further reveals a consistent positive correlation between interlocking and the principal orientation angle of strong normal contact forces,as well as a correlation between i

关键词： Granular material Interlocking Shear resistance Direct shear Discrete element method Vibro-compaction

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The pros and cons of biological effects of herbs and herb-derived compounds on liver tumorigenesis

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hepatoma Research 2022年第1期8卷 257-277页

作者： Mohamad Khalil Maria Calasso Leonilde Bonfrate Agostino Di Ciaula Maria De Angelis david q.h.wang Piero Portincasa Clinica Medica“Augusto Murri” Department of Biomedical Sciences and Human OncologyUniversity of Bari Medical SchoolBari 70124Italy Department of Soil Plant and Food SciencesUniversity of Bari Aldo MoroBari 70126Italy Department of Medicine and Genetics Division of Gastroenterology and Liver DiseasesMarion Bessin Liver Research CenterEinstein-Mount Sinai Diabetes Research CenterAlbert Einstein College of MedicineNew YorkNY 10461USA

Consumption of natural products such as herbs,spices,plant-derived compounds,and foods is on the rise globally.The use of these substances is widely recognized as an integral part of culture and tradition,with the philosophy being“no benefit is no harm”.The utility of medicinal plants and extracts is under scrutiny,and the scientific community needs to clarify many conceptual gaps.Medicinal plants are rich in bioactive phytochemicals that produce chemopreventive effects at different levels,including cellular,animal,and clinical.The ultimate translational value is often missing,and some studies suggest that botanicals may contain toxic compounds that cause acute or chronic toxicity.In this regard,the liver is the center,and herbal products can show protective effects or induce hepatotoxicity,thereby promoting liver cancer.In this review article,we examine a range of herbal products implicated in hepatocarcinogenesis and extend the discussion to herbal products that may be potentially involved in the prevention and treatment of liver carcinoma.

关键词： herbs hepatocellular carcinoma liver cancer natural compounds

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