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Hepatocellular carcinoma clinical update: Current standards and therapeutic strategies

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Liver Research 2020年第4期4卷 180-190页

作者： steven d.colquhoun department of Surgery University of California DavisSacramentoCAUSA

Hepatocellular carcinoma(HCC)accounts for the vast majority of primary hepatic *** overall incidence of this disease has always been significant,but in recent years it has continued to rise,now making HCC one of the leading causes of cancer deaths ***,research into the mechanisms of carcinogenesis and treatment options for this disease has also been progressing *** the future for new insights and therapies appears more promising than ever,it also remains important to understand both the nature of HCC and the current state-of-the-art for treating affected *** surgery is often considered to be a first choice,many patients present with extensive disease and are therefore not operative ***,significant clinical advances over the last decade have contributed a number of new or improved treatment *** of these treatments require expertise from a variety of different clinical ***,managing patients with HCC has rapidly become a multi-modality,multi-disciplinary endeavor in which the details of each in-dividual’s circumstance can greatly impact outcomes,and strategies can be quite *** purpose of this review is to provide a perspective on the disease itself,the patients who become afflicted,the spectrum of currently available treatment options,and the strategies for their optimal *** knowledge can be critically important as new data become available on the research front.

关键词： Hepatocellular carcinoma(HCC) Ablation Transarterial chemoembolization(TACE) High intensity focused ultrasound(HIFU) Stereotactic body radiation therapy(SBRT) Irreversible electroporation(IRE) Liver surgery Liver transplantation

Overexpression of Galectin-1 and Galectin-3 in hepatocellular carcinoma

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Liver Research 2020年第4期4卷 173-179页

作者： Tahereh Setayesh steven d.colquhoun Yu-Jui Yvonne Wan department of Pathology and Laboratory Medicine University of California DavisSacramentoCAUSA department of Surgery University of California DavisSacramentoCAUSA

Galectins(Gals)are evolutionarily conserved proteins that bind to b-galactoside containing *** expression of Gals is associated with the development,progression,and metastasis of different types of *** the 11 Gals identified in humans,the roles of Gal-1 and Gal-3 have been extensively investigated in various ***,we summarize the roles of overly expressed Gal-1 and Gal-3 in the pathogenesis of hepatocellular carcinoma(HCC).The overexpression of Gal-1 and Gal-3 correlates with tumor growth,HCC cell migration and invasion,tumor aggressiveness,metastasis,and poor prognosis.A potentially promising future treatment strategy for HCC may include the combination of immunotherapy with Gal-1 *** research is warranted to investigate targeting Gal-1 and Gal-3 for HCC treatment.

关键词： Galectin-1(Gal-1) Galectin-3(Gal-3) Liver cancer Hepatocellular carcinoma(HCC) Fibrosis Cirrhosis Non-alcoholic steatohepatitis(NASH) Metastasis Epithelial-mesenchymal transition(EMT)

Hepatocellular carcinoma immunotherapy:The impact of epigenetic drugs and the gut microbiome

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Liver Research 2020年第4期4卷 191-198页

作者： Farzam Vaziri steven d.colquhoun Yu-Jui Yvonne Wan department of Pathology and Laboratory Medicine University of California DavisSacramentoCAUSA department of Surgery University of California DavisSacramentoCAUSA

The incidence of hepatocellular carcinoma(HCC)has been increasing for *** disease has now risen to become the sixth most common malignancy overall,while ranking as the third most frequent cause of cancer *** several surgical interventions and loco-regional treatment options are available,up to 80%of patients present with advanced disease not amenable to standard ***,traditional cytotoxic chemotherapeutic agents are notoriously ineffective and essentially play no role in the management of affected *** has led to an enormous need for more effective sys-temic therapeutic *** recent years,immunotherapy has emerged as a potentially viable and exciting new alternative for the treatment of *** the current immunotherapeutic options remain imperfect,various strategies can be employed to further improve their *** findings have revealed epigenetic modulation can be effective as a new approach for improving HCC *** the gut microbiome(gut-liver axis)can also be an interesting subject in this ***,we explore the latest insights into the role of immunotherapy treating HCC,both mono and in combination with other *** also focus on the impact of epigenetic drugs and the microbiome in the overall effectiveness of HCC immunotherapy.

关键词： Hepatocellular carcinoma(HCC) Immunotherapy Gut microbiota Epigenetic drugs Combination therapy

Hepatocellular carcinoma diagnosis and treatment: An overview

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Liver Research 2020年第4期4卷 159-160页

作者： steven d.colquhoun Yu-Jui Yvonne Wan department of Surgery University of California DavisSacramentoCAUSA department of Pathology and Laboratory Medicine University of California DavisSacramentoCAUSA

For decades,chronic liver disease has remained an increasing global health *** vaccines and antiviral therapies,both hepatitis B and C remain enormous clinical *** steatosis has become a rapidly increasing worldwide concern that can be appropriately characterized as an evolving epidemic.1 Aroundtheworld alcohol consumption is onthe rise,while autoim-mune conditions and environmental toxins all continue contrib-uting to this seemingly universal health *** common denominator of chronic liver disease is progressive hepatic inflam-mation leading to fibrosis and cirrhosis.

关键词： diagnosis clinical treatment

Einstein’s Concept of Clock Synchronization Conflicts with the Second Relativity Postulate

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Journal of Modern Physics 2024年第7期15卷 985-1000页

作者： steven d. deines donatech Corporation Inc. Fairfield Iowa USA

Einstein defined clock synchronization whenever photon pulses with timetags traverse a fixed distance between two clocks with equal time spans ineither direction. Using the second relativity postulate, he found clocksmounted on a rod uniformly moving parallel with the rod’s length cannot besynchronized, but clocks attached to a stationary rod can. He dismissed thisdiscrepancy by claiming simultaneity and clock synchronization were not commonbetween inertial frames, but this paper proves with both Galilean and Lorentztransformations that simultaneity and clock synchronization are preservedbetween inertial frames. His derivation means moving clocks can never besynchronized in a “resting” inertial frame. Ultraprecise atomic clocks intimekeeping labs daily contradict his results. No algebraic error occurred inEinstein’s derivations. The two cases of clocksattached to a rod reveal three major conflicts with the currentsecond postulate. The net velocity between a photon source and detector plusthe “universal” velocity c is mathematically equivalent toEinstein’s clock synchronization method. As the ultraprecise timekeepingcommunity daily synchronizes atomic clocks on the moving Earth withultraprecise time uncertainty well below Einstein’s lowest limit ofsynchronization, the theoretical resolution of the apparent conflict isaccomplished by expanding the second relativity postulate to incorporate thenet velocity between the photon source and detector with the emitted velocity c as components of the total velocity c. This means the magnitudeof the total photon velocity can exceed the speed limit (299792458 m/s) set by the standard velocity c. .

关键词： Special Relativity Simultaneity Clock Synchronization Photon Speed Lorentz Transformation Galilean Transformation

Relational and Euclidean Temporal Space

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Journal of Applied Mathematics and Physics 2024年第2期12卷 683-719页

作者： steven d. P. Moore Independent Researcher Milton Canada

In mathematics, space encompasses various structured sets such as Euclidean, metric, or vector space. This article introduces temporal space—a novel concept independent of traditional spatial dimensions and frames of reference, accommodating multiple object-oriented durations in a dynamical system. The novelty of building temporal space using finite geometry is rooted in recent advancements in the theory of relationalism which utilizes Euclidean geometry, set theory, dimensional analysis, and a causal signal system. Multiple independent and co-existing cyclic durations are measurable as a network of finite one-dimensional timelines. The work aligns with Leibniz’s comments on relational measures of duration with the addition of using discrete cyclic relational events that define these finite temporal spaces, applicable to quantum and classical physics. Ancient formulas have symmetry along with divisional and subdivisional orders of operations that create discrete and ordered temporal geometric elements. Elements have cyclically conserved symmetry but unique cyclic dimensional quantities applicable for anchoring temporal equivalence relations in linear time. We present both fixed equivalences and expanded periods of temporal space offering a non-Greek calendar methodology consistent with ancient global timekeeping descriptions. Novel applications of Euclid’s division algorithm and Cantor’s pairing function introduce a novel paired function equation. The mathematical description of finite temporal space within relationalism theory offers an alternative discrete geometric methodology for examining ancient timekeeping with new hypotheses for Egyptian calendars.

关键词： Relationalism Pairing Function Equation discrete Euclidean Timelines Ancient Timekeeping

Friction and wear performance of polyether ether ketone(PEEK)polymers in three lubrication regimes

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Friction 2024年第4期12卷 670-682页

作者： davide MASSOCCHI Nora LECIS Marco LATTUAdA davide SCAGLIA steven CHATTERTON Paolo PENNACCHI department of Mechanical Engineering Politecnico di MilanoMilan 20156Italy Eni SpA Downstream product R&DLombardia 20097Italy Eurobearings S.R.L. Lombardia 29016Italy

This experimental study investigates the friction and wear of three coatings commonly used in industrial applications,particularly in hydrodynamic *** three materials under investigation were Babbitt,polyether ether ketone(PEEK)reinforced with 15%carbon fibers,and PEEK reinforced with 20%carbon *** first polymer material was extruded,while the other was produced by fused deposition modelling(FdM).The materials were subjected to sliding tests in a pin-on-disc configuration,with a steel ball serving as the counter *** tests were conducted at room temperature,with a load of 10 N and under three different lubrication conditions:dry,grease,and *** linear speed was set at 0.3 m/s for the dry and semi-solid lubrication tests,while for the oil tests,the speed was set at 0.25 m/*** greases used had consistency grades of NGLI 000 and NGLI *** ISO VG 68 circulation oil was used for the oil lubrication ***,thermodynamic analyses were performed under the most severe conditions(i.e.,dry)to investigate the steel-Babbitt and steel-PEEK contact.

关键词： hydrodynamic bearings polyether ether ketone(PEEK)polymers additive manufacturing grease lubrication sliding oil lubrication ball-on-disk tribology

Exploring unconventional attributes of red blood cells and their potential applications in biomedicine

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Protein & Cell 2024年第5期15卷 315-330页

作者： Alkmini T.Anastasiadi Vasiliki-Zoi Arvaniti Krystalyn E.Hudson Anastasios G.Kriebardis Constantinos Stathopoulos Angelo d’Alessandro steven L.Spitalnik Vassilis L.Tzounakas department of Biochemistry School of MedicineUniversity of Patras26504 PatrasGreece department of Pathology and Cell Biology Columbia University Irving Medical CenterNew York CityNY 10032USA Laboratory of Reliability and Quality Control in Laboratory Hematology(HemQcR) Department of Biomedical SciencesSchool of Health&Caring SciencesUniversity of West Attica(UniWA)12243 EgaleoGreece department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus13001 AuroraCOUSA Present address:Institute for Fundamental Biomedical Research(IFBR) Biomedical Sciences Research Center“Alexander Fleming”Vari11527 AthensGreece

We need to talk about red blood *** cells are defined as cells containing distinct nuclei and other membranous ***,red blood cells(RBCs)lack a nucleus and organelles—perhaps to limit the generation of reactive oxygen species(Zhang et al.,2011)—and are filled with hemoglobin(Hb).This oxygen carrier is limited to the cytosol by the cell membrane and cytoskeleton,which maintain cellular integrity and deformability as RBCs pass through narrow capillaries(Gratzer,1994)to perform their primary function of gas exchange.

关键词： membranous maintain

Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVId-19

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World Journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K Jacobs steven d Morley Kay Samuel Katie Morgan Lyndsey Boswell Timothy J Kendall david A dorward Jonathan A Fallowfield Peter C Hayes John N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUNd Metabolic dysfunction-associated steatotic liver disease(MASLd),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVId-19),while preexisting MASLd increases the risk of LI and the development of COVId-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVId-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLd and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLd were determined in formalin-fixed liver tissue sections across the MASLd pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVId-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLd *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVId-19 COVId-19-associated cholangiopathy