简介:Thereversetranscriptase(RT)proteinofhepatitisBvirus(HBV)hasbeensuccessfullyexpressedbyrecombinanttechnologyinEschericahiacoli(E.coli).Inthisstudyweaimedtodevelopasemi-quantitativeassayforthestudyofHBVRTproteinusingthissystem.CompleteHBVpolymerasegenefromawildtypevirus(rt306P)andthepolymerasegenefromamutant,withrt306Psubstitutedbyserine(rtP306S)wereseparatelyfusedtothemaltosebindingprotein(MBP)geneandexpressedinE.colirespectively.TheexpressionlevelsofHBVpolymerasegenesfromthewildtypevirusanditscounterpartmutantatrt306werecompared.Whentheseproteinsweresemi-quantifiedbyWesternblottingusingrabbitanti-TPserum,thertP306SmutantshoweddecreasedexpressionofMBP-HBVpolymerase.Bythismethod,wehaveshownthattheexpressionlevelofHBVRTcouldbeaffectedbysubstitutionsinitsaminoacidsequences,andthismethodcouldbeusedtostudythecharacteristicsofHBVRTprotein.
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简介:AbstractAs human life expectancy continues to increase and the birth rate continues to decline, the phenomenon of aging is becoming more prominent worldwide. Therefore, addressing the problems associated with global aging has become a current research focus. The main manifestations of human aging are structural degeneration and functional decline of aging tissues and organs, quality of life decline, decreased ability to resist diseases, and high incidence rates of a variety of senile degenerative diseases. Thus far, no ideal treatments have been found. Stem cell (SC) therapies have broad application prospects in the field of regenerative medicine due to the inherent biological characteristics of SCs, such as their plasticity, self-renewal, and multidirectional differentiation potential. Thus, SCs could delay or even reverse aging. This manuscript reviews the causes of human aging, the biological characteristics of SCs, and research progress on age reversal.
简介:Ameloblastomaisabenignbutlocallyaggressiveodontogenieneoplasmthataccountsfor10%ofalltumorsarisinginthemandibleandmaxilla(1).Eightypercentofameloblastomasariseinthemandible,andtheyareusuallyfoundinyoungadults.Itfrequentlyrecursifnotadequatelyresected.Therefore,thestandardtherapyforthistumoriscompleteboneresectionwithanadequatemarginofsafety:marginalorsegmentalosteotomy.However,aestheticdeformities,functionalimpairmentsandpsychologicalimpairmentsafterradicalsurgeryforlargeameloblastoma,havebeenseriousissues(1).
简介:Objective:ToinvestigatetheeffectsofE7080andN5-(1-iminoethyl)-L-ornithinedihydrochloride(L-NIO)oncolorectalcanceraloneandincombination.Methods:HT29colorectalcancercelllinefromSapInstitutewasused.Real-timecellanalysis(xCELLigencesystem)wasperformedtodeterminetheeffectsofE7080andL-NIOoncolorectalcellproliferation.WhileapoptosiswasdeterminedwithAnnexinVstaining,andtheeffectofagentsonangiogenesiswasdeterminedwithchorioallantoicmembrane(CAM)model.Results:WefoundthatE7080hasastrongantiproliferativeeffectwithanhalfmaximuminhibitionofconcentration(IC50)valueof5.60×10–8mol/L.AlsoithasbeenobservedthatE7080showedantiangiogenicandapoptoticeffectsonHT29colorectalcancercells.AntiangiogenicscoresofE7080were1.2,1.0and0.6for100,10and1nmol/LE7080concentrations,respectively.Furthermore,apoptosishasbeendetectedin71%ofHT29colorectalcancercellsafteradministrationof100nmol/LE7080whichmayindicatestrongapoptoticeffect.MeanwhileadministrationofL-NIOalonedidnotshowanyeffect,butthecombinationofE7080withL-NIOincreasedtheantiproliferative,antiangiogenicandapoptoticeffectsofE7080.Conclusions:ResultsofthisstudyindicatethatE7080maybeagoodchoiceintreatmentofcolorectaltumors.FurthermoretheincreasedeffectsofE7080whencombinedwithL-NIOraisethepossibilitytousealowerdoseofE7080andthereforeavoid/minimizethesideeffectsobservedwithE7080.
简介:AbstractReverse genetics via targeted modification of gene sequences to obtain a phenotype and the inference of a gene's function or regulatory mechanism is widely used as a potent tool in viral biology and application. However, while reverse genetics has contributed significantly to our understanding of molecular biology and the pathogenesis of viruses, its accessibility (operation) and openness (data) have raised many concerns regarding biosafety and biosecurity. In this review, we retrospectively examine the development of reverse genetics and its applications in virology, then emphasize global biosafety and biosecurity concerns regarding reverse genetics, and summarize global regulations, governance, and laws on reverse genetics. This review seeks to enhance our understanding and rational application of reverse genetics technology for the benefit of humankind.
简介:AbstractLow-level viremia (LLV) was defined as persistent or intermittent episodes of detectable hepatitis B virus (HBV) DNA (<2000 IU/mL, detection limit of 10 IU/mL) after 48 weeks of antiviral treatment. Effective antiviral therapies for chronic hepatitis B (CHB) patients, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), have been shown to inhibit the replication of HBV DNA and prevent liver-related complications. However, even with long-term antiviral therapy, there are still a number of patients with persistent or intermittent LLV. At present, the research on LLV to address whether adversely affect the clinical outcome is limited, and the follow-up treatment for these patients is open to question. At the same time, the mechanism of LLV is not clear. In this review, we summarize the incidence of LLV, the association between LLV and long-term outcomes, possible mechanisms, and management strategies in these patient populations.
简介:Inrecentyears,intravascularultrasound(IVUS)follow-upisalwaysusedintheevaluationofthedevelopmentofatherosclerosis,anditcanalsobeusedastheendpointofdrugtherapyinclinicalobservation.Since1994,thefirststatinlipid-lowering4Sexperimentresultswasreported,thefollowingstatinforlipid-loweringtestsrepresentedbyREVERSALPROVE-IT,TNT,IDEAL,ASTEROIDandJUPITERstronglyconfirmedthatfurtherreducetheefficacyoflow-densitylipoproteincholesterol(LDL-C)(toenhancethelipid-loweringtreatment)accesstoincreaseeffectofthecardiovascularprotectionandalsoreversetheplaques'progress.Butscholars'opinionsonthemeritsanddemeritsofenhancestatincholesterol-loweringtherapyhasbeenindebate.Wereviewtherecentworkonstatinsandreversalofarterialplaquesforanumberofclinicalstudies.
简介:AbstractBackground:Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods:We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.Results:At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions:The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration:ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx
简介:Cisplatindamagescochlearhaircellsandspiralganglionneuronsthroughcelldeathsignalingpathwaysthatarenotfullyunderstood.Weusedfocusedapoptosisgenemicroarraystostudyearlychangesingeneexpres-sionincochlearculturesfromP3neonatalratstreatedwithcisplatin(0.2mM).After12hoursofcisplatintreat-ment,morethan50%ofthe96genesonthearrayshowedasignificantdecreaseinexpression,consistentwithwidespreadcelldeath.However,after3hoursofcisplatintreatment,10genesshowedsignificantincreaseinex-pressionintotalcochleartissue.Inexperimentswithsubsetsofcochleartissues,at3h,cisplatininducedincreasedexpressionof12genesinthecochlearsensoryepithelium(basilarmembrane)and11genesinthespiralganglion(tissueofRosenthal'scanal,containingthespiralganglion).Theseincludedpro-andanti-apoptoticgenesin-volvedinthep53signalingpathway,TNFreceptorfamily,NF-kappaBpathway,deathdomainfamily,deatheffec-tordomainfamily,Bcl-2family,CARDfamily,TRAFfamily,andGTPsignaltransduction.Althoughthechangesingeneexpressionshowedanoverlapbetweenbasilarmembraneandspiralganglion,otherchanges,whichmayreflecttheuniqueresponseofeachtissue,werealsoobserved.Pifithrin-αblockedcisplatin-inducedup-regulationofgenesinthep53signalingpathwaywhenassayedbybothsuperarrayandrealtimePCR.Thedataaddtoourunderstandingoftheinvolvementofp53incisplatin-inducedototoxicityandotoprotection,conferredbythep53inhibitorPifithrin-α.
简介:AbstractFor the detection of steatosis, quantitative ultrasound imaging techniques have achieved great progress in past years. Magnetic resonance imaging proton density fat fraction is currently the most accurate test to detect hepatic steatosis. Some blood biomarkers correlate with non-alcoholic steatohepatitis, but the accuracy is modest. Regarding liver fibrosis, liver stiffness measurement by transient elastography (TE) has high accuracy and is widely used across the world. Magnetic resonance elastography is marginally better than TE but is limited by its cost and availability. Several blood biomarkers of fibrosis have been used in clinical trials and hold promise for selecting patients for treatment and monitoring treatment response. This article reviews new developments in the non-invasive assessment of non-alcoholic fatty liver disease (NAFLD). Accumulating evidence suggests that various non-invasive tests can be used to diagnose NAFLD, assess its severity, and predict the prognosis. Further studies are needed to determine the role of the tests as monitoring tools. We cannot overemphasize the importance of context in selecting appropriate tests.
简介:ObjectiveThisstudywasinitiallydesignedtoevaluatetheeffectofcelecoxibontheregimenof5-fluorouracil,epirubicin,andcyclophosphamide(FEC)combination,followedbydocetaxel(T)inneoadjuvantsetting.AnunplannedpreliminaryreviewonsafetywasconductedafterahaltofthestudyduetotheconcernedpotentialcardiovascularriskofusingCOX-2inhibitors.MethodsWestudied23consecutivecasesofoperablebreastcancerhavingreceivedfourcyclesofFEC(500mg/m2,100mg/m2,500mg/m2)followedbyfourcyclesofT(100mg/m2)withconcurrentcelecoxib(400mgtwicedaily)(groupA)orsamechemotherapyregimenbutwithoutconcurrentcelecoxib(groupB).Thesecombinedchemotherapieswereadministeredevery3weeks.TheChi-squaretestorFisher'sexacttestwereusedtoassessthedifferenceinincidenceoflimitinghematologicaltoxicitesbetweengroups.Results23patients(groupA:n=12;groupB,n=11)receivedatotalof183outof184plannedtreatmentcycles;one(4%,1/23)ofthemomittedthefourthcycleofFECowingtorepeatedincidencesoffebrileneutropenia.Receiveddoseintensity(RDI)forFECingroupA(90%±11%)washigherthanthatingroupB(80%±8%)whileRDIforTwassimilarbetweengroupA(93%±8%)andgroupB(96%±9%).Ofthefirst91treatmentcyclesofFEC,limitinghematologicaltoxicity,severeneutropeniaincludingfebrileneutropenia,wassignificantlydifferentbetweengroupAandB[(10.4%,5/48)vs.(32.6%,14/43),P=0.009].Othertoxicitiescommonlyobservedinchemotherapyreceivingpatientsweremanageable.ConclusionsNeoadjuvantuseofFECfollowedbyTwithconcurrentcelecoxibappearedtobesafefortreatmentofoperableinvasivebreastcancer.Theobservedlowerincidenceofchemotherapy-inducedneutropeniaispossiblycontributedbytheadministrationofCOX-inhibitor.WebelievethatfurtherinvestigationmightprovidemoreevidenceontheuseofCOX-2inhibitorsinbreastcancer.
简介:客观;为了评估临床的申请并且在皮肤上讨论反向的背面的掌部的拍动和它的复合拍动的起作用的指示,hand.Methods背叛:从1990~2003,我们使用了反向的背面的掌部的拍动和它的复合拍动在122种情况中修理手指的软织物缺点,它与腱接枝,神经接枝或骨头接枝包括了反向的掌部的拍动的90个盒子和它的复合拍动的32个盒子。基于后续观察,我们分析了在比较tocontralateral的掌部的拍动和它的复合拍动,手术后的轮廓,拍动颜色和质地回顾地摸的颠倒的指示。结果:在122个盒子的系列,熬过的拍动和施主地点缺点直接被关上。后续时期从1-12年。拍动和它的复合拍动的Thepostoperative轮廓,颜色和质地类似于正常手指的那些,尽管线性疤留下了。根据感觉恢复的标准(英国医药研究委员会,BMRC),拍动的感觉功能在操作以后恢复了S31年。在有拍动与腱接枝对待的腱缺点的10种情况中,手指的屈曲扩展的功能用全部的活跃运动的测量的方法与相反地侧面的手指相比恢复了50%-75%。在有不属于工会的phalangeal或拍动与骨头接枝对待的骨头缺点的7种情况中,联合为3months.Conclusions发生在操作以后:到有骨头或腱暴露的手指上的软织物缺点,反向的掌部的拍动和它的复合拍动是为修理的一种更好的选择。修理的范围直到手指的远侧的interphalangeal关节。第二根背面的掌部的动脉象脉管的小花梗的选择更一致、更大,与另外的背面的掌部的动脉比较。手术后的拍动颜色和质地类似于正常手指。
简介:AbstractIn recent years, the research of immune checkpoint inhibitors has made a great breakthrough in lung cancer treatment. Currently, a variety of immune checkpoint inhibitors have been applied into clinical practice, including antibodies targeting the programmed cell death-1, programmed cell death-ligand 1, and cytotoxic T-lymphocyte antigen 4, and so on. However, not all patients can benefit from the treatment. Abnormal antigen presentation, functional gene mutation, tumor microenvironment, and other factors can lead to primary or secondary resistance. In this paper, we reviewed the molecular mechanism of immune checkpoint inhibitor resistance and various combination strategies to overcome resistance, in order to expand the beneficial population and enable precision medicine.