CTLA-4Ig与ICAM-1单抗联合DCp诱导同种移植耐受

目的:利用细胞毒性T淋巴细胞相关抗原4 Ig融合蛋白(CTLA-4 Ig)和细胞间黏附分子1(ICAM-1)单克隆抗体联合治疗经供者树突状细胞前体(DCp)免疫的移植受者诱导移植耐受.方法:实验分4组:对照组、CTLA-4 Ig组、ICAM-1单抗组和联合组,每组8只BALB/c受鼠.每组均以2×106C57BL/6供者DCp经尾静脉输注受鼠.CTLA-4Ig组和ICAM-1单抗组分别自DCp输注之日起连续2周向受鼠腹腔内注射CTLA-4 Ig或ICAM-1单抗(0.1 mg/d);联合组以同样剂量两药注射2周;对照组则仅输注DCp.DCp输注1周后4组均行异位心脏移植并观察移植心存活时间,进一步作皮肤移植确认耐受状态.结果:对照组、ICAM-1单抗组和CTLA-4 Ig组的C57BL/6供心平均存活时间分别为(20.13±1.64)d、(45.00±2.62)d和(90.00±3.07)d,联合组8例中除1例存活98 d外,其他7例均超过100 d.前3组C57BL/6来源皮肤平均存活时间分别为(4.25±0.89)d、(9.00±0.76)d和(44.50±3.42)d,联合组8例中1例存活91 d,3例存活95 d,其他4例均超过100 d.结论:在供者DCp输注受者后以ICAM-1单抗和CTLA-4 Ig联合处理受者能够诱导针对供者的耐受状态.     

TGF-β1、IL-10在门静脉预输注供者凋亡脾脏细胞大鼠移植心脏模型中的表达

目的 输注供者凋亡细胞建立大鼠同种异体心脏移植模型,探讨凋亡细胞诱导免疫耐受的作用机制.方法 实验动物分为3组:A组为对照组;B组为实验组,心脏移植前经门静脉输注供者来源的凋亡脾脏细胞;C组为免疫抑制剂组,移植前后给予CsA.观察各组移植心脏存活时间,组织病理学改变,血清IL-2、IL-10及TGF-β1含量,并通过单向混合淋巴细胞培养判定耐受是否具有抗原特异性.结果 B组移植心脏存活时间较A组显著延长,排斥反应程度减轻,受者对供者产生抗原特异性耐受;C组移植心脏存活时间最长,但其免疫抑制作用缺乏抗原特异性.在心脏移植术后B组血清中IL-2水平较对照组显著降低,而IL-10及TGF-β1显著升高.结论 通过预输注供者凋亡细胞的方法可以诱导大鼠同种异体心脏移植的免疫耐受,并且此种耐受具有抗原特异性.IL-10及TGF-β1在此过程中可能起着重要作用.     

负载供者抗原的第三方树突状细胞延长大鼠移植心脏存活

目的 观察负载供者抗原第三方未成熟DC对大鼠同种异体移植心脏存活期的影响.方法 培养骨髓来源第三方大鼠未成熟DC,负载供者抗原,CTLA-4 Ig致耐受处理.建立大鼠心脏腹部移植模型,A组:心脏移植;B组:心脏移植,术前输注供者源未成熟DC;C组:心脏移植,术前输注第三方未成熟DC;D组:心脏移植,术前输注负载供者抗原致耐受第三方未成熟DC.分别行移植心病理、IFNγmRNA表达和移植心存活时间观察.结果 D组的移植心病理改变轻,IFNγmRNA表达下调,移植心脏存活时间显著延长.结论 负载供者抗原第三方致耐受未成熟DC能够诱导供者特异性免疫耐受,明显延长大鼠移植心脏存活时间.     

CTLA-4 Ig融合蛋白抗小鼠同种心脏移植排斥的效果及其机制

目的：研究细胞毒性T淋巴细胞相关抗原4（CTLA－4,CD152）Ig融合蛋白（CTLA－4Ig)抗小鼠同种心脏移植排斥的效果及其体内作用的机制。方法：以C57BL／6小鼠为供,BALB／c小鼠为受行异位心脏移植术,分别腹腔注射CTLA4Ig[100μg/d,共15次]γ-球蛋白对照抗体及PBS,观察移植供心的存活时间;研究腹腔注射CTLA－4Ig后受体小鼠T细胞对同种抗原反应性的变化以及对T细胞亚群分化的影响。结果：同种心脏移植的小鼠腹腔注射CTLA－4Ig后,移植心脏存活时间较对照组显延长,40％移植心脏的存活时间长达2个月以上。CTLA－4Ig治疗后诱导受体小鼠T细胞对同种抗原低反应性,但对第三抗原的反应性无影响。受体血清中的Th1来源的IL－2、IFN－γ均明显低于PBS对照组,而Th2来源的IL－10的水平则明显高于对照组,IL－4未见明显的改变。结论：CTLA－4Ig治疗后可通过诱导受体小鼠T细胞对同种抗原低反应性以及受体T细胞由Th1向Th2分化,诱导供特异性免疫耐受的产生,显延长同种小鼠心脏移植存活期。     

NBD多肽预处理的树突状细胞延长移植心存活时间的实验研究

目的 探讨NBD多肽预处理的供体源性树突状细胞(DC)在诱导心脏移植免疫耐受中的作用及可能机制.方法 体外培养供体源性BALB/c小鼠骨髓树突状细胞并以NBD多肽预处理(NBD多肽-DC,在小鼠心脏移植前7 d,将NBD多肽.DC输至受者C57BL/6小鼠体内.应用Cu-T建立小鼠颈部异位心脏移植模型,观察心脏移植物存活时间,病理分析检测排斥反应程度.混合淋巴细胞反应(MLR)测定受者脾脏T细胞对供者同种抗原的反应性,并用ELISA方法测定受者血清Thl型细胞因子(IFN-γ和IL-12)和Th2型细胞因子(IL-4和IL-10)水平的变化.结果 NBD多肽-DC可使移植心脏存活天数延长至(21.83±3.54)d,较PBS对照组的(6.66±1.21)d明显延长(P＜0.01),降低排斥反应病理分级(Stanford 1～2级),能诱导受者脾脏T细胞的抗原特异性低反应性,使受者小鼠血清INF-γ和IL-12水平显著降低(P＜0.01).而IL-4和IL-10水平明显升高(P＜0.01).结论 NBD多肽预处理的供体源性DC能够诱导针对移植供者产生的特异性免疫耐受现象,其机制可能与诱导受者T细胞的抗原特异性低反应性及Th1/Th2免疫偏移有关.     

前列腺素A1预处理供体大鼠对心脏移植受体T细胞功能的影响

目的 研究核转录因子-κB(NF-κB)抑制剂前列腺素A1(PGA1)预处理供体大鼠,在同种心脏移植中对供心的保护及对其受体T淋巴细胞功能影响.方法 使用大鼠同种心脏移植排斥模型,观察PGA1预处理供体对心脏存活时间影响,并进行受体大鼠混合淋巴细胞培养及测定血清白介素2、白介素4(IL-2,IL4)浓度.结果 PGA1组供心存活时间较生理盐水组延长(P＜0.05),混合淋巴细胞培养显示PGA1组受体大鼠T细胞对供体抗原刺激的增殖反应较生理盐水组受到抑制(P＜0.05),PGA1组血清IL-2浓度较生理盐水组降低(P＜0.05),而两组间血清IL-4浓度无显著差异(P＞0.05).结论 PGA1预处理供体能有效延长供心存活时间,抑制受体T淋巴细胞的免疫功能.     

TGF—β诱导的调节性T细胞体内输注延长小鼠皮肤移植物存活

利用TGF-β1体外诱导naYveT细胞分化为调节性T细胞（Treg）,通过体内输注延长小鼠皮肤移植物存活时间,并研究其相关机制。根据诱导条件不同分为3组：对照组（加入IL-2培养的C57BL／6小鼠T细胞）、MLR组（即混合淋巴细胞反应组,经同种抗原刺激活化的C57BL／6小鼠T细胞）和TGF-β组（经同种抗原刺激活化的C57BL／6小鼠T细胞,同时加入5．0ng／mlTGF-β1诱导）。利用FACS检测CD4＋CD25＋T细胞比例,并用RT—PCR检测Foxp3的表达水平。建立小鼠皮肤移植模型,并于第0、1、2和3天输注上述细胞,观察皮肤移植物存活时间。     

胸腺基质淋巴细胞生成素受体剔降的未成熟树突状细胞调节哮喘小鼠Th1/Th2失衡的研究

目的树突细胞疫苗是治疗哮喘的新途径,文中探讨经鼻滴注基质淋巴细胞生成素（thymic stromal lymphopoetin,TSLP）受体剔降的未成熟树突状细胞（immature dendritic cell,imDC）对哮喘模型小鼠过敏性气道炎症及Th1/Th2免疫失衡的影响,为免疫调节治疗哮喘提供理论和实验基础。方法36只C57BL/6小鼠随机分为胸腺TSLP受体剔降的imDC治疗组（A组）、imDC治疗组（B组）和哮喘组（C组）。以卵蛋白（ovalbumin,OVA）、氢氧化铝免疫建立哮喘模型,A组和B组分别于激发前气道内滴注100μl的细胞悬液,分别含有1×106TSLPR剔降的imDC、imDC,C组气道内滴注100μl的PBS;各组激发后肺泡灌洗分析细胞组份,分离肺淋巴细胞测定细胞因子分泌水平,以流式细胞仪检测CD4＋干扰素-γ（interferonγ,IFN-γ）＋、CD4＋白细胞介素-4（interleukin-4,IL-4）＋百分比及IFN-γ＋/IL-4＋比值,比较各组肺组织学改变。结果TSLP受体剔降的imDC治疗组与其他组比较：①可明显抑制OVA抗原激发后气道内嗜酸性粒细胞的浸润（P〈0.01）;②明显抑制肺淋巴细胞产生IL-4、IL-5,增加了IFN-γ的产生;③肺淋巴细胞CD4＋IFN-γ＋百分比及IFN-γ＋/IL-4＋明显升高（P〈0.01）,而CD4＋IL-4＋百分比则明显下降（P〈0.01）;④明显抑制哮喘鼠气道内及肺泡内的过敏性炎症反应。结论激发前经鼻滴注TSLP受体剔降的imDC对哮喘小鼠过敏性气道炎症有明显的防治作用,其机制可能与抑制树突细胞TSLP-TSLP受体信号通路,调整Thl/Th2失衡有关。     

CTLA4Ig诱导免疫耐受的体外研究

目的 观察CTLA4Ig在诱导人外周血T细胞免疫耐受中的作用。方法 以结核菌素刺激人外周血淋巴细胞，观察不同剂量CTLA4Ig对外周血淋巴细胞增殖反应的影响；观察CTLA4Ig和CsA(环孢霉素A)对再次结核菌素刺激和非相关第三者APC细胞刺激淋巴细胞增殖反应的影响，IL-2的变化，以及外源性IL-2对免疫耐受诱导的影响。结果 CTLA4Ig抑制淋巴细胞增殖呈剂量依赖关系，20μg／ml时抑制作用最强；CTLA4Ig能诱导免疫耐受并与CsA有协同作用；外源性IL-2能抑制免疫耐受的诱导。结论 CTLA4Ig能抑制淋巴细胞的增殖和IL-2的分泌释放，CTLA4Ig和CsA联合应用能更彻底抑制淋巴细胞增殖和IL-2的分泌释放，并诱导免疫耐受；外源性IL-2能逆转免疫耐受。     

Th1/Th2细胞因子对心脏移植大鼠NPC输注诱导免疫耐受的作用

目的探讨大鼠血清中Th1/Th2细胞因子表达与供肝非实质细胞(NPC)输注诱导心脏移植免疫耐受的关系。方法建立大鼠心脏移植模型,将40只大鼠随机分成排斥反应组、免疫耐受组,每组20只。观察移植心脏存活时间,并检测受者血清中Th1/Th2细胞因子白细胞介素2(IL-2)、干扰素γ(IFN-γ)、白细胞介素4(IL-4)、白细胞介素6(IL-6)、白细胞介素10(IL-10)的表达水平。结果免疫耐受组供心存活时间为(30.83±2.55)d,排斥反应组为(8.15±2.08)d,差异有显著性(t=24.46,P<0.01)。术后7、14 d排斥反应组血清Th1细胞因子IL-2、IFN-γ水平均高于免疫耐受组,Th2细胞因子IL-4、IL-10表达水平均低于免疫耐受组,术后7 d血清IL-6表达水平显著高于免疫耐受组(t=4.50~16.20,P<0.01)。结论免疫耐受的形成与Th1/Th2细胞因子相互作用有关。     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

Dr.Zhang Ren''''s Experience in the Acupuncture Treatment of Different Diseases with the Same Therapeutic Principle

Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.     

Luo Lingjie''''s Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.     

猪肺磷脂注射液联合经鼻持续气道正压通气对呼吸衰竭早产儿的临床疗效及肌酸激酶同工酶活性的影响

目的 探讨猪肺磷脂注射液联合经鼻持续气道正压通气(NCPAP)对呼吸衰竭早产儿的临床疗效及肌酸激酶同工酶活性(CK-MB)的影响.方法 选取呼吸衰竭早产儿80例,分为观察组和对照组各40例.对照组采用NCPAP给氧治疗,观察组给予NCPAP给氧联合猪肺磷脂气管内给药.观察两组患儿治疗前及治疗12h、24 h后PaO2、PaCO2、血氧饱和度(SaO2)、pH的变化情况,检测治疗前及治疗5d后血清CK-MB水平;评估两组患儿的临床治疗效果.结果 两组患儿PaO2、PaCO2、SaO2、pH比较,差异均有统计学意义(P＜0.05),其中观察组治疗后的PaO2、SaO2、pH均高于对照组,PaCO2则低于对照组.两组的PaO2、SaO2、pH均随观察时间延长而升高(P＜0.05),PaCO2均随观察时间的延长而降低(P＜0.05).观察组治疗有效率为87.5％,显著高于对照组的70.0％ (P ＜0.05).治疗5d后两组患儿血清CK-MB水平均较前降低(P＜0.05),且观察组明显低于对照组(P＜0.05).结论 猪肺磷脂注射液气管内给药联合NCPAP可以显著降低呼吸衰竭早产儿CK-MB的含量,提高治疗有效率,起到很好的呼吸循环支持作用.     

Survey and practice of reporting quality of randomized controlled clinical trials on traditional Chinese medicine

Evidence obtained from randomized controlled trials （RCTs） has been generally accepted as the gold standard in the evaluation of clinical effectiveness. Readers need to understand the trial design, implementation, results, analysis and interpretation, so as to fully Jnderstand the results of RCTs. Thus, the investigators of RCTs have to report these items in a complete, accurate and clear manner. Since 1998, we have conducted several evaluations on the reporting quality of RCTs published in Chinese journals on traditional Chinese medicine （TCM） and results have shown that there is an urgent need for higher quality RCTs on TCM.     

TCM Treatment of Ankylosing Spondylitis by Tonifying the Kidney and Strengthening the Governor Vessel

Ankylosing spondylitis is a chronic and progressive disorder with inflammation mainly involving the central axis joints. It mainly affects the cervical spine and the lumbosacral area, with the pathogenesis closely related to the kidney and the Governor Vessel (GV). TCM holds that the syndrome is deficiency in origin and excess in superficiality, which is due to insufficiency of the kidney, deficiency of GV, and blocking of the channels with the invasion of exogenous evil, leading to poor circulation of qi and blood and malnutrition of the bones, muscles and joints. The TCM method of tonifying the kidney and strengthening GV to regulate circulation of qi and blood and check the arthralgia pain should be adopted, with the Kidney-Tonifying and GV Strengthening Decoction (益肾强督汤) prescribed.     

IMPROVING P-gp EXPRESSION IN HUMAN MONONUCLEAR CELLS IN VITRO TRANSFECTED BY MULTIDRUG RESISTANCE-1 mRNA

CHEMOTHERAPY playsa greatrolein the treat- ment of malignanttumors,especiallyingynecolo- gicalones.But inanticancerchemotherapy,leuko-cytopeniaisfrequentlytheprimarydose-limitingsideeffect factor.Moreover,cancersarefrequentlychemoresistantbe-causeof overexpressionof P-glycoprotein(P-gp), which isencodedby multidrugresistancegene (MDR1 ) and detectableinup to50% ofhuman cancersand renderscellsresistancetoanticancerdrugs.The safetyand potentialtherapeuticbenefitof mdr1 gene transferredto h…