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简介：AbstractMany seminal advances have been made in human immunodeficiency virus (HIV)/AIDS research over the past four decades. Treatment strategies, such as gene therapy and immunotherapy, are yielding promising results to effectively control HIV infection. Despite this, a cure for HIV/AIDS is not envisioned in the near future. A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS, referred to as "selective elimination of host cells capable of producing HIV" (SECH). Similar to the "shock and kill strategy," the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. Herein, we comprehensively review the specific mechanisms targeted by the SECH strategy. Briefly, the suggested cocktail of drugs should contain (i) latency reversal agents to promote the latency reversal process in replication-competent reservoir cells, (ii) pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways, and finally (iii) drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells, and by HIV integrase inhibitor drugs. Finally, we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.

简介：AbstractPrions are unconventional infectious agents that cause lethal transmissible neurodegenerative diseases in human and animals. Prions can be distinguished from other known pathogens by their lack of nucleic acids. The most essential process for prion propagation is conversion from normal cellular prion protein on the cell membrane to insoluble, limited protease digestion-resistant, pathogenic scrapie prion protein. For dozens of years, many pharmacological tools and interventions targeting different stages of disease progression have been developed and evaluated, and a few have been entered clinical trials. However, no approved prophylactic or therapeutic drugs for prion diseases are available. In this review, we summarize the current concepts in prion research and discuss advances in the research and development of drugs for the prevention and treatment of prion disease.

简介：the way a military general organises his army would affect the behaviour of the troops in battle. In the same way,the general must change his strategy accordingly. In other words,an existing organisation or structure should not be viewed as constraints to change if the strategy dictates that the change is necessary. In this aspect

简介：TheEuropeanSecurityandDefencePolicy(ESDP)comprisesanimportantpartoftheEU'sCommonForeignandSecurityPolicy(CFSP).TheaimofESDPistostrengthentheEU'sexternalabilitytoactthroughthedevelopmentofcivilianandmilitarycapabilitiesforinternationalconflictpreventionandcrisismanagement.InDecember2003,theEUadopteditsfirstEuropeanSecurityStrategy(ESS).Eversincethen,theimplementationoftheESShasbeenregardedasoneofthebiggestchallengesfortheEUinCFSP/ESDPmatters.Althoughmuchprogresshasbeenmadeinitsindependentsecurityanddefence-buildingprocess,EUstillfacesseriousproblemsanddifficultiesinthispolicyarea.Thispapertriestoexaminetheserecentdevelopments,assesstheirimpactsinregional-globalsecurity,andanalyzeexistingproblemsandfuturetrends.Finally,theauthoralsoexaminesEU-Chinaengagementsinrecentyearsandexplorespossibilitiesfortheirfuturecooperationintheareaofinternationalsecurity.

简介：the way a military general organises his army would affect the behaviour of the troops in battle. In the same way,the general must change his strategy accordingly. In other words,an existing organisation or structure should not be viewed as constraints to change if the strategy dictates that the change is necessary. In this aspect

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简介：AbstractChronic wounds have always been a tough fight in clinical practice, which can not only make patients suffer from pain physically and mentally but also impose a heavy burden on the society. More than one factor is relevant to each step of the development of chronic wounds. Along with the in-depth research, we have realized that figuring out the pathophysiological mechanism of chronic wounds is the foundation of treatment, while wound infection is the key point concerned. The cause of infection should be identified and prevented promptly once diagnosed. This paper mainly describes the mechanism, diagnosis and therapeutic strategies of chronic wound infection, and will put an emphasis on the principle of debridement.

简介：Accordingtothe"InternationalStandardofChineseHeadAcupoints"207patientssufferingfromstrokeweretreatedbyneedlingalongtheanteriorandposteriorobliguelinesofvertex-temporal,andtheline1andline2lateraltovertex.Themarkedlyeffectiverateaccountedfor73.43%ofthetotal,andtheoveralleffectiveraterepresented89.86%.Afterthetreatmentsomesymptomsashemiplegia,lingualdysfunction,facialandtongueparalysiswereobviouslyimproved(P<0.01).ThetherapeuticeffectofheadacupuncturewasobviouslybetterthanthatofWesternmedicine(P<0.01).Comparisonoftherapeuticeffectsmadeamongneedlingalongdifferentlinesandbetweenthoseappliedontheintactandaffectedsidesofthebodyshowedthattheywerealleffectiveinimprovingthesymptoms,buttherewasnosignificantdifference(P<0.05)

简介：AbstractBone disease is the most common complication in patients with multiple myeloma (MM), and it may lead to skeletal-related events (SREs) such as bone pain, pathological fractures, and spinal cord compression, which impair a patients' quality of life and survival. The pathogenesis of myeloma bone disease (MBD) involves disruption of bone reconstitution balance including excessive activation of osteoclasts, inhibition of osteoblasts, and participation of osteocytes and bone marrow stromal cells. Various factors, such as the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG), dickkopf-1 (DKK-1), sclerostin, and activin-A, are involved in the development of MBD. Bisphosphonates and the anti-RANKL antibody denosumab are currently the main treatment options for MBD, delaying the onset of SREs. Denosumab is preferred in patients with MM and renal dysfunction. Although effective drugs have been approved, antimyeloma therapy is the most important method for controlling bone disease.

简介：AbstractPancreatic cancer is one of the most aggressive malignancies. The poor prognosis of pancreatic cancer patients is mainly attributed to low diagnostic rate at the early stage, highly aggressive nature coupled with the inadequate efficacy of current chemotherapeutic regimens. Novel therapeutic strategies are urgently needed for pancreatic cancer. MicroRNAs (miRNAs) play an important regulatory role in key processes of cancer development. The aberrant expression of miRNAs is often involved in the initiation, progression, and metastasis of pancreatic cancer. The discovery of tumor suppressor miRNAs provides prospects for the development of a novel treatment strategy for pancreatic cancer. We reviewed recent progress on the understanding of the role of miRNAs in pancreatic cancer, highlighted the efficient application of miRNAs-based therapies for pancreatic cancer in animal models and clinical trials, and proposed future prospects. This review focuses on the promise of integrating miRNAs into the treatment of pancreatic cancer and provides guidance for the development of precision medicine for pancreatic cancer.

简介：Parkinsonsdisease(PD)isacommon,progressiveneurodegenerativediseasecharacterisedbydegenerationofnigrostriataldopaminergicneurons,aggregationofα-synucleinandmotorsymptoms.Currentdopamine-replacementstrategiesprovidesymptomaticrelief,howevertheireffectivenesswearoffovertimeandtheirprolongeduseleadstodisablingside-effectsinPDpatients.ThereisthereforeacriticalneedtodevelopnewdrugsanddrugtargetstoprotectdopaminergicneuronsandtheiraxonsfromdegenerationinPD.Overrecentyears,therehasbeenrobustevidencegeneratedshowingthatepigeneticdysregulationoccursinPDpatients,andthatepigeneticmodulationisapromisingtherapeuticapproachforPD.Thisarticlefirstdiscussesthepresentevidenceimplicatingglobal,anddopaminergicneuron-specific,alterationsinthemethylomeinPD,andthetherapeuticpotentialofpharmacologicallytargetingthemethylome.Itthenfocusesonanothermechanismofepigeneticregulation,histoneacetylation,anddescribeshowthehistoneacetyltransferase(HAT)andhistonedeacetylase(HDAC)enzymesthatmediatethisprocessareattractivetherapeutictargetsforPD.Itdiscussestheuseofactivatorsand/orinhibitorsofHDACsandHATsinmodelsofPD,andhowtheseapproachesfortheselectivemodulationofhistoneacetylationelicitneuroprotectiveeffects.Finally,itoutlinesthepotentialofemployingsmallmoleculeepigeneticmodulatorsasneuroprotectivetherapiesforPD,andthefutureresearchthatwillberequiredtodetermineandrealisethistherapeuticpotential.

简介：Venomousanimalsontheearthhavebeenfoundtobevaluableresourcesforthedevelopmentoftherapeutics.Enzymaticandnon-enzymaticproteinsandpeptidesarethemajorcomponentsofanimalvenoms,manyofwhichcantargetvariousionchannels,receptors,andmembranetransporters.Comparedtotraditionalsmallmoleculedrugs,naturalproteinsandpeptidesexhibithigherspecificityandpotencytotheirtargets.Inthisreview,wesummarizethevarietiesandcharacteristicsoftoxinsfromafewrepresentativevenomousanimals,anddescribethecomponentsandapplicationsofanimaltoxinsaspotentialdrugcandidatesinthetreatmentofhumandiseases,includingcancer,neurodegenerativediseases,cardiovasculardiseases,neuropathicpain,aswellasautoimmunediseases.Inthemeantime,therearemanyobstaclestotranslatenewtoxindiscoverytotheirclinicalapplications.Thechallenges,strategies,andperspectivesinthedevelopmentoftheproteintoxin-baseddrugsarediscussedaswell.

简介：Acupuncturetherapywasadoptedintreating17patientssufferingfrompostherpeticneuralgia.Localacupointwasselectedasthemainpointandsomepointsontherelatedmeridiansasadjunctpoints,whichwerepuncturedonceaday,10successivedaysasatreatmentcourse.Itwasre-vealedthatthetotaleffectiveratewas88.24%and22.22%inacupuncturegroupandcontrolgrouprespectively(P<0.01).Andthehigheffectiverateswereobservedinthe2ndand3rdcourseofthetreatmentandinthepatientswhosecoursesofdiseaseswereinonemonth.ltissuggestedthatacupuncturewassimple,physiologicallymoderateandeffectivetherapyinthetreatmentofposther-peticneuralgia.

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简介：AIM:Toevaluatetheeffectivenessofbariumimpactiontherapyforpatientswithcolonicdiverticularbleeding.METHODS:WereviewedtheclinicalchartsofpatientsinwhomtherapeuticbariumenemawasperformedforthecontrolofdiverticularbleedingbetweenAugust2010andMarch2012atYokohamaRosaiHospital.Twentypatientswereincludedinthereview,consistingof14menand6women.Themedianageofthepatientswas73.5years.Thedurationofthefollowupperiodrangedfrom1to19mo(median:9.8mo).Amongthe20patientswere11patientswhorequiredtheprocedureforre-bleedingduringhospitalization,6patientswhorequireditforre-bleedingthatdevelopedafterthepatientleftthehospital,and3patientswhorequiredtheprocedureforthepreventionofrebleeding.Barium(concentration:150w%/v%)wasadministeredpertherectum,andtheleadingedgeofthecontrastmediumwasfolloweduptothececumbyfluoroscopy.Afterconfirmationthattheascendingcolonandcecumwerefilledwithbarium,theenematubewaswithdrawn,andthepatient’spositionwaschangedevery20minfor3h.RESULTS:Twelvepatientsremainedfreeofrebleedingduringthefollow-upperiod(range:1-19mo)afterthetherapeuticbariumenema,including9menand3womenwithamedianageof72.0years.Re-bleedingoccurredin8patientsincluding5menand3womenwithamedianageof68.5years:4developedearlyre-bleeding,definedasre-bleedingthatoccurswithinoneweekaftertheprocedure,andtheremaining4developedlatere-bleeding.TheDFI(disease-freeinterval)decreased0.4for12mo.Onlyonepatientdevelopedacomplicationfromtherapeuticbariumenema(colonicperforation).CONCLUSION:Therapeuticbariumenemaiseffectiveforthecontrolofdiverticularhemorrhageincaseswheretheactivebleedingsitecannotbeidentifiedbycolonoscopy.

简介：目的：观察针刺治疗失眠症的疗效。方法：将96例失眠症患者按就诊顺序分成2组，治疗组51例，采用针刺治疗；对照组45例，口服艾司唑仑片治疗。治疗2星期后，进行疗效比较。结果：治疗组总有效率为94．1％，对照组总有效率77．7％，两组总有效率差异有统计学意义（P〈0．01）。结论：针刺治疗失眠症疗效优于口服艾司唑仑片。

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简介：平坦破裂是的王牌的解剖结构复杂、起作用的暴露和固定是极其困难的。因为那些显然代替了王牌平坦破裂，更靠近的引出被注定引起致丑陋的愈合。有内部固定(ORIF)的开的减小不仅导致解剖减小，而且带复杂并发症。不管哪个方法将被采用，创伤的关节炎或大腿骨的头的脉管的坏死可能发生。以便treatacetabular更有效地断裂，矫形外科医生应该被要求充分为复杂并发症预防掌握theacetabular解剖，简历力学，分类和必要知识。