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简介：AbstractObjective:Cardiovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk. The effects of drugs on individual usage are also often unknown. This review aimed to examine the correlation between depression and common cardiovascular drugs, develop more potent interventions for depression in cardiovascular patients, and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression.Data sources:The data in this review were obtained from articles included in PubMed, EMBASE, and Web of Science.Study selection:Clinical trials, observational studies, review literature, and guidelines about depression and cardiovascular drugs were selected for the article.Results:We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review. Statins have been proven to have antidepressant effects. Some studies believe angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARB) can exert an antidepressant influence by acting on the renin-angiotensin system, but further clinical trials are needed to confirm this. Beta-blockers have previously been associated with depression, but the current study found no significant association between beta blockers and the risk of depression. Aspirin may have antidepressant effects by suppressing the immune response, but its role as an antidepressant remains controversial. calcium channel blockers (CCBs) can regulate nerve signal transduction by adjusting calcium channels, but whether this effect is beneficial or harmful to depression remains unclear. Finally, some cases have reported that nitrates and diuretics are associated with depression, but the current clinical evidence is insufficient.Conclusions:Statins have been proven to have antidepressant effect, and the antidepressant effects of ACEIs/ARB and aspirin are still controversial. CCBs are associated with depression, but it is unclear whether it is beneficial or harmful. No association has been found with β-blockers, diuretics, and nitrates.

简介：AbstractFluid resuscitation is an essential intervention in critically ill patients, and its ultimate goal is to restore tissue perfusion. Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions, hypoperfusion, shock, and so forth, leading to disturbed microcirculatory perfusion and organ dysfunction. Therefore, maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy. Like drugs, however, different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx. The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx. Many animal studies have shown that normal saline might be associated with glycocalyx degradation, but clinical studies have not confirmed this finding. Hydroxyethyl starch (HES), rather than other synthetic colloids, may restore the glycocalyx. However, the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies. Some studies have suggested that albumin may restore the glycocalyx, whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation. Notably, most studies did not correct the effects of the infusion rate or fluid volume; therefore, the results of using balanced crystalloids remain unclear. Moreover, mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity, and this still requires confirmation by high-quality clinical studies.

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简介：Howtodesignclinicaltrialsformedicaldevicesisaproblemplaguingtheindustrytoday.Astherearemanydifferencesinclinicaltrialsofmedicaldevicesanddrugs.Thispaperdescribesthedifferencesofthetwopointsfromtheperspectivsofdefinitionofmedicaldevicesanddrugs,scope,phasing,subjectsanddesignofclinicaltrialsindetails,aimingtohelptherelatedpersonnelmakescientificdecisionswhileconductingclinicaltrialdesignformedicaldevices.

简介：Anovelpressurizedcapillaryelectrochromatography(PCEC)wasdevelopedtoseparatebaxicdrugsonstrongcationexchange(SCX)column.TheseparationresultbyusingPCECwasbetterthanthatbyusingmicro-HPLC.Theeffectsofelectricalfieldandpressureonplateheightandresolutionwereinvestigated.Influencesoforganicmodifier,ionicstrengthandpHvalueofbufferonretentionbehaviorwereevaluated,andtheseparationmechanismwasalsodiscussed.

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简介：Objective:Toanalyzequantitativelythesynergisticandantagonisticeffectsofcombinedoxymatrine(OMT)and5-fluorouracil(5-GU)onacelllineofhumanlivercancer(HepG2)withmedian-effectprincipleinvitro.Methods:Themedian-effectprincipleandMTTmethodwereusedinthequantitativeanalysisofeffectsofthetwodrugs.Results:Cytotoxicactivityoftheindividualdrugsenhancedasdrugconcentrationincreased.Asfa=0.41,aCIequalto1indicatedadditivity;fa<0.41,aCIlessthan1indicatedsynergy;andfa>0.41,aCIgreaterthan1indicatedantagonism.Thesequenceofadministrationdidnotinfluencethecytotoxicactivityofthecombinedantitumordrugs.Theratioofdrugconcentrationwasafactorthatcaninfluencethekillingeffect.Conclusion:Thecombineddrugsinteraction(CI<1)wassynergisticatlowerconcentrationandantagonisticathigherconcentration.Theratioofdrugconcentrationisafactorthatcaninfluencethekillingeffect.

简介：Softand3D-printedmicromachinescanbeimplantedinthebodytodeliverdosesofachemodrug.Thisstrangenewbiobotusesneitherbatterynorwires,andcanbecontrolledfromoutsidethebodytodeliveradoseoncommand.It’sagadgetwellsuitedforthisneweraofpersonalizedmedicine.

简介：On80patientswithabnormalfetalposition,weobservedtheeffectsofmoxibustioncombinedwithChineseherbsonthepositionoffetus.Theresultssuggestthistherapyispracticalandeffective.

简介：Manystudiesdemonstratethatconventionalanticancerdrugselevateintracellularlevelofreactiveoxygenspecies(ROS)andalterredox-homeostasisofcancercells.ItiswidelyacceptedthatanticancereffectofthesechemotherapeuticsisduetoinductionofoxidativestressandROS-mediatedapoptosisincancer.Ontheotherhand,theharmfulsideeffectsofconventionalanticancerchemotherapyarealsoduetoincreasedproductionofROSanddisruptionofredox-homeostasisofnormalcellsandtissues.ThisarticledescribesthemechanismsfortriggeringandmodulationofapoptosisthroughROS-dependentandROS-independentpathways.Wetrytoanswerthequestion:'Isitpossibletoinducehighlyspecificapoptosisonlyincancercells,withoutoverproductionofROS,aswellaswithoutharmfuleffectsonnormalcellsandtissues?'Thereviewalsosuggestsanewtherapeuticstrategyforselectivekillingofcancercells,withoutsignificantimpactonviabilityofnormalcellsandtissues,bycombininganticancerdrugswithredox-modulators,affectingspecificsignalingpathwaysandavoidingoxidativestress.

简介：Electroacupuncture(EA)hasbeenclinicallyusedtotreatdepressionandhasresultedinfavorableeffectsinChina.However,resultsfromanimalstudiesandpathologydonotreflecttheinfluenceofelectroacupuncturetreatmentoninvivophysiologicalfunctions.Tothoroughlyanddynamicallyobservepathologicalchangesduringdepression,thepresentstudyestablishedEA+fluoxetineandfluoxetinegroupstoobservedepressioninpatients.1H-magneticresonancespectroscopywasutilizedtodeterminethecorrelationbetweenhippocampalfrontallobemetabolitechangesandmentaldisorderscale.ResultsrevealedsignificantlyincreasedN-acetylaspartate(NAA)/creatine(Cr)inthebilateralhippocampusandrightfrontallobeofdepressionpatientstreatedwithEAcomparedwithfluoxetine.ChangesinNAA/Crinbilateralhippocampusandrightfrontallobeinbothgroups,beforeandaftertreatment,negativelycorrelatedwithseverityandcurativeeffects.Choline/Crchangesinthebilateralfrontallobesofbothgroupsweresignificantbeforeandaftertreatment,butnegativelycorrelatedwithcurativeeffects.Choline/CrchangesinthebilateralhippocampusweresignificantintheEA+fluoxetinegroupbeforeandaftertreatment,butnegativelycorrelatedwithseverityandthecurativeeffectsofdepression.Theseresultsdemonstrateabnormalbiochemicalmetabolisminbilateralfrontallobesandhippocampusofdepressionpatients,andshowthatEAsignificantlyalteredbiochemicalindicesinthefrontallobesandhippocampuscomparedwithfluoxetine.

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简介：AbstractBackground:The burden of human immunodeficiency virus (HIV) infection in people who use drugs (PWUD) is significant. We aimed to screen HIV infection among PWUD and describe their retention in HIV care. Besides, we also screen for hepatitis C virus (HCV) infection among HIV-seropositive PWUD and describe their linkage to care.Methods:We conducted a prospective study in 529 PWUD who visited the "Cañada Real Galiana" (Madrid, Spain). The study period was from June 1, 2017, to May 31, 2018. HIV diagnosis was performed with a rapid antibody screening test at the point-of-care (POC) and HCV diagnosis with immunoassay and PCR tests on dried blood spot (DBS) in a central laboratory. Positive PWUD were referred to the hospital. We used the Chi-square or Fisher’s exact tests, as appropriate, to compare rates between groups.Results:Thirty-five (6.6%) participants were positive HIV antibodies, but 34 reported previous HIV diagnoses, and 27 (76%) had prior antiretroviral therapy. Among patients with a positive HIV antibody test, we also found a higher prevalence of homeless (P < 0.001) and injection drug use (PWID) (P < 0.001), and more decades of drug use (P= 0.002). All participants received HIV test results at the POC. Of the 35 HIV positives, 28 (80%) were retained in HIV medical care at the end of the HIV screening study (2018), and only 22 (62.9%) at the end of 2020. Moreover, 12/35 (34.3%) were positive for the HCV RNA test. Of the latter, 10/12 (83.3%) were contacted to deliver the HCV results test (delivery time of 19 days), 5/12 (41.7%) had an appointment and were attended at the hospital and started HCV therapy, and only 4/12 (33.3%) cleared HCV.Conclusions:We found almost no new HIV-infected PWUD, but their cascade of HIV care was low and remains a challenge in this population at risk. The high frequency of active hepatitis C in HIV-infected PWUD reflects the need for HCV screening and reinforcing the link to care.

简介：Naturalproducts(NPs)arecompoundsthatarederivedfromnaturalsourcessuchasplants,animals,andmicroisms.Therapeuticshasbenefitedfromnumerousdrugclassesderivedfromnaturalproductsources.TheBiopharmaceuticsDrugpositionClassificationSystem(BDDCS)wasproposedtoserveasabasisforpredictingtheimportanceoftransportersandenzymesindeterminingdrugbioavailabilityanddisposition.Itcategorizesdrugsintooneoffourbiopharmaceuticalclassesaccordingtotheirwatersolubilityandextentofmetabolism.Thepresentpaperreviews109drugsfromnaturalproductsources:29%belongtoclass1(highsolubility,extensivemetabolism),22%toclass2(lowsolubility,extensivemetabolism),40%toclass3(highsolubility,poormetabolism),and9%toclass4(lowsolubility,poormetabolism).HereinweevaluatedthecharacteristicsofNPsintermsofBDDCSclassforall109drugsaswellsasforsubsetsofNPsdrugsderivedfromplantsourcesasantibiotics.Inthe109NPsdrugs,wepiled32drugsfromplants,50%(16)oftotalinclass1,22%(7)inclass2and28%(9)inclass3,nonefoundinclass4;Meantime,theantibioticswerefound5(16%)inclass2,22(71%)inclass3,and4(13%)inclass4;nodrugwasfoundinclass1.Basedonthisclassification,weanticipateBDDCStoserveasausefuladjunctinevaluatingthepotentialcharacteristicsofnewnaturalproducts.

简介：DrugsSPD-304(6,7-dimethyl-3-{[methyl-(2-{methyl-[1-(3-trifluoromethyl-phenyl)-1H-indol-3-ylmethyl]-amino}-ethyl)-amino]-methyl}-chromen-4-one)andzafirlukastcontainacommonstructuralelementof3-substitutedindolemoietywhichcloselyrelatestoadehydrogenatedreactioncatalyzedbycytochromeP450s(CYPs).ItwasreportedthatthedehydrogenationcanproduceareactiveelectrophilicintermediatewhichcausetoxicitiesandinactivateCYPs.DrugL-745,870(3-{[4-(4-chlorophenyl)piperazin-1-yl]-methyl}-1H-pyrrolo2,3-β-pyridine)mighthavesimilareffectsinceitcontainsthesamestructuralelement.Weusedmoleculardockingapproachcombinedwithmoleculardynamics(MD)simulationtomodelthree-dimensional(3D)complexstructuresofSPD-304,zafirlukastandL-745,870intoCYP3A4,respectively.Theresultsshowthatthesethreedrugscanstablybindintotheactivesiteandthe3-methylenecarbonsofthedrugskeepareasonablereactivedistancefromthehemeiron.ThecomplexstructureofSPD-304-CYP3A4isinagreementwithexperimentaldata.Forzafirlukast,thecalculationresultsindicatethat3-methylenecarbonmightbethedehydrogenationreactionsite.DockingmodelofL-745,870-CYP3A4showsapotentialpossibilityofL-745,870dehydrogenatedbyCYP3A4at3-methylenecarbonwhichisinagreementwithexperimentinvivo.Inaddition,residuesinthephenylalanineclusteraswellasS119andR212playacriticalroleintheligandsbindingbasedonourcalculations.ThedockingmodelscouldprovidesomecluestounderstandthemetabolicmechanismofthedrugsbyCYP3A4.