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1.
目的:探讨脱氢表雄酮(DHEA)对去势鼠CD4+T细胞Th1/Th2型细胞因子表达和成骨细胞(OB)增殖的影响。方法:建立小鼠绝经后骨质疏松(PMO)模型,分为OVX组、OVX+DHEA组、OVX+E2组。另设Sham组为假手术对照。取腰椎和股骨行骨组织形态计量分析;流式细胞术(FCM)检测各组鼠脾脏CD4+T细胞内IL-2、IFN-γ(Th1型)和IL-4、IL-10(Th2型)的表达;并取椎骨植块法培养OB,FCM分析增殖细胞核抗原(PCNA)表达。结果:OVX组与Sham组相比,椎骨和股骨骨小梁面积显著下降(P〈0.01),说明PMO模型成功建立;与OVX组相比,OVX+DHEA组腰椎、股骨及OVX+E2组腰椎、股骨骨小梁面积都明显增加(P〈0.01)。OVX组IL-2及IFN-γ表达显著低于Sham组(P〈0.05);而OVX+DHEA组和OVX+E2组显著高于OVX组(分别为P〈0.01和P〈0.05)。OVX+DHEA组IL-4及IL-10表达显著低于OVX组(P〈0.01)。OVX组IFN-γ/IL-4比值明显低于Sham组(P〈0.05);OVX+DHEA组和OVX+E2组IFN-γ/IL-4比值均显著高于OVX组(P〈0.01)。OVX组OB的PCNA表达与Sham组相比显著增高(P〈0.05);与OVX组相比,OVX+DHEA组OB核内PCNA的平均表达强度和阳性细胞百分率皆显著增高(分别为P〈0.05和P〈0.01)。OVX+DHEA组OBPCNA表达与CD4+T细胞IFN-γ水平呈明显正相关(r=0.931,P〈0.05);与IL-4水平呈负相关(r=-0.815,P〈0.05)。结论:DHEA可通过细胞免疫调节作用形成Th1型免疫偏移,从而显著改善PMO的免疫状态;并有效促进OB增殖,显著改善骨形态。  相似文献   

2.
目的建立去卵巢联合糖皮质激素致兔骨质疏松模型,探讨去卵巢联合糖皮质激素对兔骨代谢的影响。方法将18只新西兰雌兔随机分为3组:假手术组(SHAM,生理盐水5 ml·kg-1·d-1);去卵巢组(OVX,生理盐水5 ml/kg/d);去卵巢联合糖皮质激素组(OVX+GC,地塞米松1 mg·kg-1·d-1)。实验第0、3和6周,检测各组大白兔腰椎(3~6)和右侧股骨的骨密度。实验结束时,取右侧股骨进行生物力学检测;取第3腰椎进行骨组织形态计量学检测。结果与SHAM组相比,OVX+GC组大白兔骨密度、骨生物力学性能(最大载荷、断裂载荷等)、骨小梁面积百分数、骨小梁厚度和骨小梁数量均显著降低(P<0.05),骨小梁分离度显著升高(P<0.05),而OVX组大白兔的均无显著差异。结论去卵巢联合糖皮质激素法建立兔骨质疏松模型切实可行,而且效果优于单纯去卵巢兔骨质疏松模型。  相似文献   

3.
目的探讨骨髓间充质干细胞(BMMSCs)尾静脉注射对体内破骨细胞活性及骨质疏松治疗作用。方法选用8周龄健康雌性小鼠行双侧卵巢切除术(OVX),建立绝经后骨质疏松模型。选用同一批次、周龄相同、体质量相近的健康小鼠行双侧卵巢附近脂肪组织部分切除,建立假手术组(sham)。对OVX组小鼠尾静脉注射BMMSC治疗,1个月后分别取双侧股骨行TRAP染色及mciro-CT检测体内破骨细胞数量和骨小梁微结构改变。结果 OVX+BMMSC注射组中破骨细胞的数量较OVX不治疗组显著降低。micro-CT显示OVX+BMMSC组骨小梁数量及骨密度显著高于OVX不治疗组。结论尾静脉注射骨髓间充质干细胞能够抑制体内破骨细胞活性,对绝经后骨质疏松具有一定的治疗作用。  相似文献   

4.
研究频率为50Hz不同强度正弦交变电磁场(SEMFs)对大鼠峰值骨量(PBM)的影响,为电磁场临床试验提供理论依据。将30只6周龄SD实验大鼠随机分为3组(n=10),对照组、0.1mT磁场组和0.6mT磁场组。磁场组分别给予不同强度磁场干预3h/d、8周后,检测骨密度(BMD)、生物力学、血清骨钙素(OC)和血清抗酒石酸酸性磷酸酶5b(TRACP 5b)以及以stevenol蓝品红苦味酸染色(VG)进行骨形态分析。实验结果表明,0.1mT磁场组大鼠全身骨密度、股骨、椎骨骨密度和股骨最大载荷显著高于对照组(P0.01),股骨和椎骨屈服强度及血清生化指标显著优于对照组(P0.05),骨小梁宽度、骨小梁数目均有增加,骨小梁间隙减小。0.6mT组与对照组相比,差异无统计意义(P0.05)。说明50Hz 0.1mT电磁场能增加SD大鼠骨密度,改善骨组织微结构,增强骨强度,从而提高大鼠的峰值骨量。  相似文献   

5.
目的了解深圳地区维生素D(VitD)缺乏性佝偻病(vitamin D deficient rickets)患儿25羟基维生素D3(25-OH-VitD3)和骨碱性磷酸酶(B-ALP)水平及维生素D受体(VDR)基因FokI rs2228570f/F位点单核苷酸多态性(SNPs)分布特征,并探讨其多态性与25-OH-VitD3和B-ALP水平之间的相关性。方法选择2017年5月~2020年3月在医院确诊为VitD缺乏性佝偻病患儿132例为研究组,同期健康儿童100名为对照组,分别检测25-OH-VitD3和B-ALP水平,同时采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测VDR基因FokI rs2228570f/F位点多态性。结果 VitD缺乏性佝偻病患儿25-OH-VitD3水平为49.62±9.75 nmol/L,明显低于对照组的73.80±12.63nmol/L,而B-ALP为287.16±37.05 mmol/L,明显高于对照组的194.58±26.68mmol/L,差异有统计学意义(P0.05);VitD缺乏性佝偻病患儿VDR基因FokI rs2228570f/F位点FF基因型及F等位基因检出率分别为44.70%和60.98%,明显高于对照组的23.00%和37.08%,差异有统计学意义(P0.05),而fF基因型检出率之间差异无统计学意义(P0.05);携带FF基因型的VitD缺乏性佝偻病患儿25-OH-VitD3水平明显低于其它基因型,而B-ALP水平明显高于其它基因型,差异均有统计学意义(P0.05);VitD缺乏性佝偻病患儿25-OH-VitD3水平明显降低,而B-ALP水平明显升高,经Pearson相关性分析,两者呈负相关(r=-0.5709,P0.05)。结论 VitD缺乏性佝偻病患儿VDR基因FokI rs2228570f/F位点多态性突变与25-OH-VitD3和B-ALP水平有关,其中FF基因型可能是深圳地区VitD缺乏性佝偻病患儿发病的易感遗传基因之一。  相似文献   

6.
绝经后骨质疏松症模型体视学测量和机理初探   总被引:1,自引:1,他引:0  
目的:观测去势术后大鼠骨组织体视学的改变,复制绝经后骨质疏松症的动物模型,初步探讨骨质疏松症的发病机制。方法:将31只3月龄雌性SD大鼠随机分为卵巢切除术组(OVX)和假手术组(sham),术后28d和56d分别处死。测量子宫湿重,骨矿物密度(BMD)和骨组织形态计量参数,分析骨组织微结构的变化。结果:OVX组术后28d和56d大鼠子宫湿重和股骨远端1/3处骨密度均显著少于sham组(P<0.05);OVX组股骨远端和胫骨近端的干骺端骨小梁面积百分率显著少于sham组(P<0.01)。结论:卵巢切除术后大鼠股骨远端骨矿物密度和骨组织形态计量学参数稳步下降,胫骨近端骨矿物密度和骨组织形态计量学参数迅速下降而且不稳定;雌激素减少导致的骨质疏松主要发生在长骨的干骺端,骨骺受影响较少;骨组织形态计量参数中骨小梁面积百分比敏感性和稳定性较高。  相似文献   

7.
背景:雌孕激素联合治疗绝经后骨质疏松症不仅能减轻雌激素的不良反应,而且能增强疗效,越来越引起关注。目的:验证雌孕激素联合对去卵巢雌性SD大鼠骨密度和骨组织形态计量学的作用。方法:雌性SD大鼠随机分为5组。假手术组仅行开关术;其余各组大鼠双侧卵巢切除。雌二醇组和雌二醇+左炔诺孕酮组术后给予17β-雌二醇10μg/(kg?d)灌饲,左炔诺孕酮组和雌二醇+左炔诺孕酮组术后给予18-甲左炔诺孕酮60μg/(kg?d)灌饲,假手术组和卵巢切除组予等量生理盐水灌饲。实验12周后处死大鼠。采用DEXA骨密度仪测定全身骨密度,截取第4腰椎进行骨形态计量学静态参数和动态参数的测量,测定骨代谢生化指标。结果与结论:卵巢切除组和左炔诺孕酮组全身骨密度、股骨质量低于假手术组、雌二醇组和雌二醇+左炔诺孕酮组(P0.05),雌二醇+左炔诺孕酮组和雌二醇组差异无显著性意义(P0.05)。与假手术组比较,卵巢切除组和左炔诺孕酮组骨小梁面积百分数、骨小梁厚度、骨小梁数量下降(P0.05),骨小梁分离度增加(P0.05),骨矿化沉积率、骨表面积骨形成率、骨体积骨形成率和骨组织体积骨形成率增加(P0.05)。与卵巢切除组相比,雌二醇组和雌二醇+左炔诺孕酮组骨小梁面积百分数、骨小梁厚度、骨小梁数量上升(P0.05),骨小梁分离度降低(P0.05),骨表面积骨形成率和骨体积骨形成率降低(P0.05)。雌二醇+左炔诺孕酮组和雌二醇组上述指标比较,均差异无显著性意义(P0.05)。结果证实,17β-雌二醇和左炔诺孕酮联合应用可增加骨密度,降低骨转换率,且无明显抑制骨形成作用。  相似文献   

8.
辛伐他汀对去卵巢骨质疏松大鼠股骨生物力学的影响   总被引:2,自引:0,他引:2  
目的研究辛伐他汀(Simvastatin,SIM)对去卵巢(OVX)骨质疏松大鼠股骨生物力学性能的影响。方法48只3月龄雌性SD大鼠,随机分成3组,假手术(SHAM)组、OVX组和OVX+SIM组,每组8只。适应性喂养一周后进行手术。术后8周开始给药,OVX+SIM组给予SIM 5mg.kg-1·d-1,其余两组用等量生理盐水灌服。用药后第4周每组随机处死半数大鼠,12周后处死剩余大鼠,取股骨进行三点弯曲试验,检测股骨最大载荷、弹性载荷、最大桡度、弹性桡度、弯曲刚度系数、弯曲韧度系数等生物力学性能。结果(1)用药4周,最大载荷:SHAM组较OVX组明显增加(P<0.05);弹性载荷:OVX+SIM组较OVX组明显降低(P<0.05);最大桡度:SHAM组较OVX组明显增加(P<0.05);弯曲韧度系数:OVX+SIM组较OVX组明显增加(P<0.01)。(2)用药12周,最大载荷:OVX+SIM组、SHAM组较OVX组明显增加(P<0.05,P<0.01);弹性载荷:OVX+SIM组较OVX组明显增加(P<0.05);弯曲韧度系数:OVX+SIM组、SHAM组较OVX组明显降低(P<0.05,P<0.01)。(3)用药12周较4周,OVX+SIM组最大载荷、弹性载简明显增加(P<0.01),OVX组弯曲韧度系数明显增加(P<0.01)。结论SIM能促进去势大鼠骨的再建,改变骨的空间微结构和骨组织有机成分和无机成分的比例及结合,随时间的延长能提高股骨的强度。  相似文献   

9.
目的探讨DMB能否促进骨髓间充质干细胞(BMSCs)向成骨细胞分化,促进骨形成,缓解由于小鼠去除卵巢引起的骨质疏松。方法体外培养BMSCs,将细胞分为对照组、成脂诱导组、成脂诱导+DMB(10-7、10-8和10-9mol/L)、成骨诱导组和成骨诱导+DMB(10-7、10-8和10-9mol/L)。分别通过油红O染色和茜素红染色鉴定BMSCs的多向分化能力。将8周C57BL/6雌鼠分为对照组、卵巢去除(OVX)组和OVX+DMB(1 mg/kg·d)组,共3组,每组10只。DMB连续给药2个月,观察骨量和骨小梁的形成。结果BMSCs纯度达91.2%,DMB以浓度和时间依赖的方式促进BMSCs增殖(P0.05)。DMB促进BMSCs向成骨细胞分化,但抑制向脂肪细胞分化。此外DMB可以显著地提高骨体积/组织体积(BV/TV)、骨小梁数量和厚度(P0.05),促进骨形成。结论 DMB能够促进BMSCs向成骨细胞分化,抑制向脂肪细胞分化,改善由于雌激素缺乏导致的骨质疏松,促进骨形成。  相似文献   

10.
目的:观察紫草素(shikonin)对人宫颈癌HeLa细胞凋亡(apoptosis)和自噬(autophagy)的影响,并初步探讨PI3K/Akt/mTOR信号通路在其中的可能作用。方法:以紫草素作用于HeLa细胞后,采用CCK-8检测细胞活力;Annexin V/PI双染法检测细胞凋亡;GFP-LC3质粒转染HeLa细胞后观察自噬小体;紫草素分别与自噬抑制剂3-甲基腺嘌呤(3-methyladenine,3-MA)和凋亡抑制剂Z-DEVD-FMK共同作用后,Western blot分析检测细胞内自噬和凋亡相关蛋白微管相关蛋白1轻链3 (LC3)和cleaved caspase-3表达的变化,并检测PI3K/Akt/mTOR信号通路中磷酸化PI3K(p-PI3K)、磷酸化Akt(p-Akt)和磷酸化mTOR(p-mTOR)蛋白表达的变化。结果:紫草素显著抑制HeLa细胞活力(P0.05)。与对照组比较,紫草素可诱导HeLa细胞凋亡(P0.05)。GFP-LC3质粒转染分析结果显示,HeLa细胞经紫草素作用后,细胞质中出现绿色点状聚集的自噬小体,而对照组细胞中极少观察到点状聚集的自噬小体形成。与紫草素组比较,紫草素+3-MA组中LC3-II/LC3-I显著降低,而cleaved caspase-3表达显著升高(P0.05);与紫草素组比较,紫草素+Z-DEVD-FMK组LC3-II/LC3-I显著升高,而cleaved caspase-3表达显著降低(P0.05)。与对照组比较,紫草素可使p-PI3K、p-Akt和p-mTOR表达明显降低(P0.05)。结论:论紫草素能诱导HeLa细胞凋亡和自噬,且其凋亡及自噬具有协同作用,其机制可能与抑制PI3K/Akt/mTOR信号通路有关。  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   

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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.
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   

18.
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   

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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