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1.
IL-11在大鼠→小鼠异种骨髓移植中对急性GVHD的预防作用   总被引:4,自引:1,他引:3  
接受致死剂量全身照射的BALB/c小鼠静脉注射SD大鼠骨髓细胞4×107和脾细胞4×107/只。处理组从移植前2d~后7d给予皮下注射重组人IL-11,监测存活率及GVHD的发病率,检测受鼠血清TNF-α、IFN-γ与IL-4水平,做混合淋巴细胞培养(MLC)检测脾细胞的增殖状况及TNF-α、IFN-γ与IL-4产量。结果发现与对照组相比,IL-11处理组GVHD发病高峰期后移,程度减轻,生存期明显延长。IL-11处理组的脾细胞增殖明显低于对照组,加入外源性IL-11可抑制淋巴细胞的增殖。处理组淋巴细胞的IL-4产量是对照组的3倍,而IFN-γ与TNF-α产量下降,血清浓度测定的结果与体外培养的结果相符。结果证实在大鼠→小鼠异种骨髓移植中短期给予IL-11能有效地减轻致死性GVHD。  相似文献   

2.
sGVHD小鼠结肠IEL细胞CD137 和Th1细胞因子的表达   总被引:1,自引:0,他引:1  
目的研究协同刺激分子CD137和Th1类细胞因子在小鼠同基因型移植物抗宿主疾病(sGVHD)中的作用。方法受体鼠用同基因型骨髓移植后,用环孢菌素A(CsA)诱导3周建立小鼠sGVHD模型;从小鼠结肠中分离上皮内淋巴细胞;用流式细胞术测定细胞亚群,RT-PCR方法检测CD137和Th1类细胞因子的表达,^3H掺入法测定T细胞增殖的抑制。结果sGVHD时,小鼠病变器官结肠上皮内淋巴细胞(IEL)中CD137及Th1类细胞因子(IL-12,IFN—γ,TNF-α)表达较正常,而移植对照组明显增高(P〈0.01);IFN-γ的增高始于环胞霉素A诱导治疗后3周,而CDl37和IL-12、TNF-α表达增高仅在出现GVHD样症状时,Th2类细胞因子(IL-4、IL-10)在GVHD的诱导和发生中均无明显改变。  相似文献   

3.
目的 通过慢病毒载体介导的鼠叉状头螺旋转录因子(Foxp3)基因表达构建鼠基因工程调节性T细胞(Tr),探讨输注基因工程Tr细胞对小鼠异基因骨髓移植后移植物抗宿主病(GVHD)的影响.方法 利用慢病毒载体介导,将鼠Foxp3基因转导入BALB/c小鼠的CD4+CD25-T淋巴细胞,即为基因工程Tr细胞.建立小鼠异基因骨髓移植模型,在移植时联合输注基因工程Tr,通过受鼠移植后生存期、组织病理学改变、炎性细胞因子浓度等指标评价其防治GVHD的作用.并与单纯照射组、移植对照组、空载体对照组相比较.结果 单纯照射组、移植对照组、工程Tr组和空载体对照组小鼠存活时间分别为(8.8±0.6)d、(36.7±2.5)d、(51.6±4.0)d和(34.1±2.3)d,工程Tr组小鼠存活时间明显长于其他各组(P<0.05).移植对照组及空载体对照组小鼠肝脏、皮肤和小肠病理切片均存在GVHD病理改变,工程Tr组长期存活小鼠的肝脏、皮肤和小肠常规病理切片结构基本正常,未见GVHD病理表现.移植后移植对照组、工程Tr组、空载体对照组受鼠血清IFN-γ、IL-2和TNF-α浓度在21~28 d时达高峰,工程Tr组在21 d时IFN-γ、IL-2和TNF-α浓度高峰较其他两组为低(P<0.05).结论 小鼠异基因骨髓移植时联合输注基因工程Tr细胞可通过减少受鼠移植后炎性细胞因子的分泌有效减少GVHD的发生,减轻其严重程度.  相似文献   

4.
NK细胞在异基因骨髓移植中作用的动物实验研究   总被引:1,自引:0,他引:1  
本文探讨NK细胞在异基因小鼠骨髓移植GVHD和GVL反应中的作用。受体小鼠以60 Co照射 ,总剂量 8 0Gy;骨髓细胞经尾静脉注入受体小鼠中 ;GVHD反应指标包括 (1)弓背体位、大小便及脱毛等一般表现 ;(2 )嵌合体、体内混合淋巴细胞反应、 30d生存率为检测GVHD反应的定量指标 ;GVL作用指标包括外周血白细胞总数及白血病细胞比例 ,脾脏白血病细胞浸润比例 ,以及死亡率观察 ;病理学检查作为鉴别GVL实验中是否主要死于GVHD的指标。GVHD反应结果表明 ,异基因与后输NK细胞的异基因骨髓移植组均于 15d内死亡。而先输NK细胞组的GVHD反应明显减轻 ,30d死亡率为5 1%。同时输NK细胞组 30d内死于GVHD反应。移植后第 7天与 15d时 ,以先输NK细胞组的嵌合率高 ,第 30天时各组均未检出明显嵌合体存在。GVL作用实验方面 ,异基因、同时输NK细胞组及后输NK细胞的骨髓移植组虽然于 12d内表现出抗白血病作用 ,但在 30d内相继死于GVHD反应。先输NK细胞组于移植后 12d开始观察到较明显GVHD样反应 ,而外周血或脾细胞中L615细胞比例变化结果证实该移植途径具有较好的抗白血病作用。先输注供体NK细胞的异基因骨髓移植方式既能减轻GVHD反应 ,又能保留较好的GVL作用  相似文献   

5.
目的检测神经干细胞移植后大鼠脑内细胞因子的变化,为营造有利于细胞移植的微环境和神经免疫调节治疗做准备。方法实验检测时间点为移植后1周、2周、4周,在SPF级SD大鼠内随机抽取8只为正常对照组,模型成功稳定的大鼠随机分为生理盐水模型对照组和神经干细胞移植组,每组每个时间点各8只,分别进行脑立体定位注射神经干细胞和生理盐水,到检测时间点时取纹状体制备好样本,用酶联免疫吸附试验双抗体夹心法检测各实验组各时间点纹状体的TNF-α、IL-1β、IFN-γ和IL-4的含量。结果与正常组相比,模型组的TNF-α、IL-1β、IFN-γ、IL-4含量都升高(P<0.05)。与模型组相比,移植组的TNF-α和IL-1β含量降低(P<0.05),IFN-γ和IL-4含量在1周、4周时升高(P<0.05),2周时无差异。与正常组相比,移植组的TNF-α含量在1周、4周时无差异,在2周时稍低(P<0.05),移植组的IL-1β含量在1周时无差异,2周时下降(P<0.05),4周时升高(P<0.05),移植组的IFN-γ和IL-4含量在各时间点均升高(P<0.05)。结论神经干细胞移植入帕金森模型鼠后引起了相关细胞因子的改变,即与模型对照组相比TNF-α、IL-1β水平下降和IFN-γ、IL-4水平升高,说明神经干细胞移植后会使宿主微环境内的部分促炎因子(TNF-α、IL-1β)下降,抗炎因子(IL-4)升高,同时伴随具有神经再生和保护作用的促炎因子(IFN-γ)的升高。  相似文献   

6.
人骨髓造血细胞经腹腔内和尾静脉注射移植SCID鼠的研究   总被引:5,自引:0,他引:5  
目的 :比较腹腔内与尾静脉注射对SCID鼠进行异种骨髓移植的体内植入能力及GVHD的发生情况 ,为异种骨髓移植构建银屑病动物模型奠定基础。方法 :密度梯度离心法分离正常人骨髓单个核细胞 (BMMNC) ,以 4× 10 7的剂量分别经尾静脉和腹腔注射移植于经γ射线预照射的SCID鼠 ,移植后观察GVHD反应及外周血白细胞恢复动力学 ,并采用流式细胞术检测小鼠外周血及骨髓中人源性CD4 5 + 细胞比例 ,观察嵌合状态。结果 :单纯尾静脉注射移植组 ,在移植后 2周即出现明显GVHD症状 ,12周仅存活 1例 ;尾静脉注射结合CsA +MTX处理组 ,个别小鼠出现轻度GVHD表现 ,12周存活率 80 % (8 10 ) ;而经腹腔内注射者移植后出现轻度GVHD症状 ,之后逐渐恢复正常 ,12周存活率 70 % (7 10 )。移植后外周血白细胞动力学恢复情况、外周血及骨髓中人CD4 5 + 细胞比例 ,尾静脉注射结合CsA +MTX处理者与经腹膜腔内注射者二组间比较无显著性差异。结论 :人骨髓造血细胞可以顺利地由SCID鼠腹腔归巢到骨髓造血组织 ,并能重建骨髓造血 ,腹腔内注射的移植方式不影响植入能力 ,既可达到骨髓移植的目的 ,又可减少GVHD的发生及反应强度  相似文献   

7.
目的 检测比较间充质干细胞(MSCs)移植治疗对烧伤大鼠炎症相关指标白细胞(WBC)、C反应蛋白(CRP)、干扰素γ(IFN-γ)、肿瘤坏死因子α(TNF-α)、白介素-6(IL-6)、白介素-10(IL-10)水平变化的影响,探讨MSCs移植治疗烧伤的抑炎机制、效果及临床意义.方法 取正常新生儿脐带,分离脐带华通氏胶,培养脐带MSCs.另取体质量为(200±5)g SD雄性大鼠制备烧伤模型并随机分为对照组和移植组,移植组在烧伤24 h后进行皮下注射MSCs移植(2×106个/只).分别于烫伤后0、1、2、3、5、7d采集血样,检测其WBC、CRP及炎症因子IFN-γ、TNF-α、IL-6、IL-10含量,并比较7、14、21、28 d时2组间创面愈合率及创面愈合时间.结果 对照组WBC烧伤后1、2d显著升高,3d后逐渐降低,移植组仅出现轻微升高;CRP水平变化比较,对照组伤后2、3d出现较大幅度上升,移植组变化甚微;血清中的炎症因子TNF-α、IL-6和IL-10比较,对照组和移植组于伤后3、5、7d均有增高,其中对照组增高更为明显;IFN-γ比较2组间未见明显差别.MSCs移植组14、21、28 d创面愈合率及创面愈合时间均明显优于对照组.结论 MSCs移植治疗烧伤大鼠,能明显减少烧伤大鼠血清中WBC、CRP、TNF-α、IL-6、IL-10的含量,减轻了由细胞炎症因子介导的炎症反应,但MSCs移植并未影响IFN-γ的产生.MSCs移植可通过降低烧伤后炎症因子产生而抑制其继发性炎症反应,从而促进创面愈合及烫伤修复.  相似文献   

8.
目的:观察间充质干细胞诱导的CD8α+Jagged2highCD11bhigh调节性树突状细胞(MSC-DCregs),对小鼠急性移植物抗宿主病(a GVHD)的影响。方法:体外诱导MSC-DCregs。以C57BL/6(H-2b)小鼠为供鼠、接受清髓性全身照射(TBI)预处理的BALB/c(H-2d)小鼠为受鼠进行移植。分为以下5组:为正常对照组;TBI组;移植组:移植物为1×107骨髓细胞(BMCs);a GVHD组:移植物为1×107BMCs+1×107脾细胞(Sp Cs);MSC-DCregs组:移植物为1×107BMCs+1×107Sp Cs+1×106MSC-DCregs。监测植入情况、H2-Kb嵌合率、a GVHD评分、生存和病理学改变。结果:处理1 0 d后所有小鼠造血恢复,30 d后嵌合率检测转为供鼠型。a GVHD组和MSC-DCregs组中位生存期分别为27 d和33 d,MSC-DCregs组生存期较a GVHD组延长(P0.01),临床评分比a GVHD组低(P0.01),33 d的皮肤、肝脏病理学改变均优于a GVHD组。结论:MSC-DCregs具有防治a GVHD的作用,其相关作用机理待进一步研究。  相似文献   

9.
目的:探究细胞因子TNF-α、IL-6和IL-8在白血病异基因造血干细胞移植后的变化和病情及预后的关系.方法:用放射免疫分析检测了白血病异基因造血干细胞移植患者(48例)、正常健康人(30例)血清TNF-α、IL-6和IL-8水平,对移植后发生或未发生急性移植物抗宿主病(aGVHD)及发生或未发生慢性移植物抗宿主病(cGVHD)进行了比较,并对预后也进行比较.结果:急、慢性GVHD组与未发生急、慢性GVHD组患者的血清TNF-α、IL-6及IL-8水平均高于正常对照组(P<0.05,除未发生cGVHD组的TNF-α浓度低外);急、慢性GVHD组与未发生急、慢性GVHD组比血清TNF-α、IL-6及IL-8水平均升高(P<0.05);移植后死亡组生存时间≤6月及>6月(除>6月的IL-8水平外)各组TNF、IL-6与IL-8水平均高于同期的存活组(P<0.05).结论:异基因造血干细胞移植术后动态监测TNF、IL-6、IL-8水平变化有助于对发生aGVHD 或cGVHD的可能提供另一种检测方法,并对判断愈后有一定的临床意义.  相似文献   

10.
目的:研究磷酸甘油酸激酶(PGK)启动子驱动的逆转录病毒载体介导单纯疱疹病毒胸苷激酶/更昔洛韦(HSV-TK/GCV)系统在小鼠异基因骨髓移植(allo-BMT)后能否减轻移植物抗宿主病(GVHD)。方法:将转HSV-TK基因的逆转录病毒感染供鼠(C57BL/6鼠)脾淋巴细胞,感染后细胞与供鼠骨髓细胞混合移植给Coγ7射线照射后的受鼠(BALB/c鼠)。移植后腹腔注射GCV,用药1周,按移植后首次给药时间,分为GCV0d组、GCV7d组、GCV12d组。观察移植后受鼠生存期、存活率、GVHD发生率及严重程度、T细胞免疫重建(CD3、CD4、CD8)及异基因嵌合等指标。结果:TK/GCV0d组、TK/GCV7d组小鼠平均生存时间分别为(26.90±4.88)d、(27.00±4.80)d,较TK/GCV12d组(21.504±3.26)d和移植对照组(15.10±O.43)d明显延长(P〈0.05),TK/GCV0d组与TK/GCV7d组之间比较差异无统计学意义(P〉0.05)。对照组小鼠12~14d100%发生Ⅲ~Ⅳ级GVHD,实验组死亡小鼠有Ⅱ~Ⅳ级GVHD病理学改变,而长期生存小鼠仅出现Ⅰ~Ⅱ级GVHD。TK/GCV0d组、TK/Gcv7d组、TK/GCV12d组在移植后5、10、15d3个时间点检测CD4^+ T细胞均高于对照组(P〈0.05),CD8^+ T细胞均低于对照组(P〈0.05)。移植后30d检测10只受鼠异基因嵌合率均在95%~100%。结论:PGK启动子驱动的逆转录病毒载体介导HSV-TK/GCV系统能有效控制小鼠allo-BMT后GVHD,移植后早期预防性用药效果优于发生GVHD后治疗性用药。  相似文献   

11.
Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc2 (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.  相似文献   

12.
Renal dysplasia and asplenia in two sibs   总被引:2,自引:0,他引:2  
A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.  相似文献   

13.
About 1900, modern food selection and processing caused widespread epidemics of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a panhypovitaminosis B, i.e., a mixture of substrate beriberi and substrate pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse endemic disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for primates. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.  相似文献   

14.
15.
Newton H 《Medical history》2011,55(2):153-182
Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.  相似文献   

16.
Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.  相似文献   

17.
HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.  相似文献   

18.
The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.  相似文献   

19.
Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.  相似文献   

20.
Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.  相似文献   

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