丙酸睾丸酮早期处理对大鼠行为及脑内多巴胺转运体的影响

目的:观察丙酸睾丸酮早期处理对大鼠行为及脑内多巴胺转运体的影响.方法:分别以开放广场实验及免疫组织化学技术观察丙酸睾丸酮处理大鼠行为及脑内多巴胺转运体(DAT)的变化.结果:开放广场实验显示早期注射丙酸睾丸酮可使大鼠活动增多,表现为水平运动、垂直运动、运动的总径长以及清洁动作次数显著增加;免疫组织化学显色结果表明丙酸睾丸酮处理组大鼠黑质和尾壳核DAT免疫反应强度增强,其灰度值显著低于对照组.结论:丙酸睾丸酮早期处理大鼠活动的增加可能与雄激素影响黑质-尾壳核多巴胺能神经体系有关.     

鼻腔给予丙酸睾丸酮对大鼠行为及中脑多巴胺能神经元的影响

目的:观察鼻腔给予丙酸睾丸酮(TP)后大鼠行为以及黑质纹状体酪氨酸羟化酶(TH)和多巴胺转运体(DAT)表达的改变.方法:对正常成年雄性及去势大鼠鼻腔给予TP 21d,分别利用开放广场实验和免疫组织化学技术观察给药后大鼠的行为及黑质和尾壳核TH及DAT的免疫反应强度变化.结果:开放广场实验结果显示正常大鼠鼻腔给予TP后水平运动得分、垂直运动得分、运动总径长比正常对照组增加;去势大鼠鼻腔给予TP后上述行为比去势组增加,但仍低于正常对照组.免疫组织化学结果显示正常大鼠鼻腔给予TP后黑质和尾壳核的TH及DAT免疫反应强度高于正常对照组;去势大鼠鼻腔给予TP后黑质和尾壳核的TH及DAT免疫反应强度高于去势组,但未达到正常对照组.结论:鼻腔给予TP增加大鼠的运动行为以及黑质和尾壳核TH和DAT的表达.     

经鼻及皮下给予睾丸酮/丙酸睾丸酮对大鼠相关脑区c-Fos表达效能的影响

目的:探讨经鼻和皮下给予睾丸酮(T)或丙酸睾丸酮(TP)对大鼠中枢神经系统相关脑区激活的效能.方法:利用放射免疫分析法检测大鼠经鼻滴注给予TP后脑脊液和血清睾丸酮浓度的变化；以免疫组织化学观察大鼠各脑区cFos的表达.结果:放射免疫结果显示去势组大鼠脑脊液和血清中睾丸酮含量比正常组降低；去势大鼠皮下注射TP后只增加了血清巾睾丸酮的含量,去势大鼠和正常大鼠经鼻给予TP后脑脊液和血清中睾丸酮的含量均明显增加；去势大鼠经鼻给予TP脑脊液巾睾丸酮的含量高于去势皮下注射TP组,而血清巾睾丸酮的含量低于去势皮下注射TP组.免疫组织化学结果显示正常大鼠鼻腔给予TP或睾丸酮增加大鼠多数脑区的c-Fos免疫反应阳性神经元数目和c-Fos免疫反应强度,而皮下注射TP只增加了少数脑区c-Fos免疫反应阳性神经元数目以及c-Fos免疫反应强度.结论:经鼻给予睾丸酮或TP后能够激活多数脑区c-Fos蛋白的表达,经鼻给予睾丸酮或TP的给药方式有可能成为治疗大雄激素低下导致的巾枢神经系统疾病的一种有效手段.     

慢性间歇性低压低氧对老年大鼠纹状体多巴胺含量及行为的影响

目的:探讨慢性间歇性低压低氧(CIHH)对老年大鼠纹状体多巴胺(DA)及其代谢产物含量以及相关行为的影响。方法:用CIHH氧仓处理大鼠30 d,通过黏附物去除实验、倾斜面实验和水平绳实验检测大鼠行为的改变,通过液相色谱-串联质谱(L,C-MS/MS)分析DA及其代谢产物二羟苯乙酸(DOPAC)和高香草酸(HVA)的含量。结果:老年组大鼠黏附物去除实验、倾斜面实验和水平绳实验中各行为参数均较成年组大鼠显著下降,CIHH处理后上述行为参数均有改善,但没有达到成年组水平;老年组大鼠DA及其代谢产物DOPAC和HVA含量均较成年组大鼠显著下降,老年CIHH组DA及其代谢产物DOPAC和HVA均升高,但没有达到正常成年组水平。结论:CIHH改善老年大鼠纹状体DA含量及行为衰退。     

经鼻给予丙酸睾丸酮增加大鼠中脑5羟色胺能神经元的表达

目的:观察经鼻给予丙酸睾丸酮(TP)后大鼠中缝背核色氨酸羟化酶(TPH)及中缝背核、尾壳核与伏核5羟色胺(5-HT)和5羟色胺转运体(SERT)表达的改变.方法:对正常成年雄性及去势大鼠经鼻给予TP 21 d,利用免疫组织化学观察给药后大鼠中缝背核TPH及巾缝背核、尾壳核与伏核5-HT和SERT的免疫反应强度变化.结果:大鼠去势处理降低中缝背核TPH及中缝背核、尾壳核与伏核5-HT和SERT的表达;去势大鼠经鼻给予TP则可提高巾缝背核TPH及巾缝背核、尾壳核与伏核5-HT和SERT的表达,但未达到假手术水平;正常大鼠鼻腔给予TP后,中缝背核TPH及中缝背核、尾壳核与伏核5-HT和SERT的表达也显著增加.结论:经鼻给予TP增加大鼠中缝背核TPH及中缝背核、尾壳核与伏核5-HT和SERT的表达,为经鼻给予TP辅助治疗衰老过程中出现的运动相关行为障碍及抑郁症状提供实验依据.     

游泳运动对老年大鼠学习记忆及伏隔核多巴胺含量和一氧化氮合酶表达的影响

目的:探讨游泳运动对老年大鼠学习记忆能力及伏隔核多巴胺含量和一氧化氮合酶(nNOS)表达的影响.方法:选择24月龄SD老年大鼠,随机分为2组,即老年对照组、游泳运动组,5月龄大鼠为成年对照组.对照组在笼内正常生活,不运动.游泳运动组采用递增负荷游泳运动,连续8周.8周后利用八臂迷宫测试大鼠空间学习记忆能力,高效液相色谱-电化学法检测各组大鼠伏隔核多巴胺含量,采用免疫组织化学结合图像半定量方法对伏隔核nNOS神经元的数量、面积及灰度进行测量和分析.结果:与成年对照组比较,老年对照组大鼠伏隔核多巴胺含量降低,完成八臂迷宫时间延长,工作记忆错误次数、参考记忆错误及总记忆错误次数均增加;与老年对照组比较,游泳运动组大鼠伏隔核多巴胺含量增高,完成八臂迷宫时间缩短,工作记忆错误次数、参考记忆错误次数及总记忆错误次数均减少.与成年对照组比较,老年对照组伏隔核nNOS免疫阳性细胞数量和阳性产物面积均减少,灰度差异没有统计学意义;与老年对照组比较,游泳运动组伏隔核nNOS免疫阳性细胞数量和阳性产物面积均增加,灰度差异无统计学意义.结论:长期游泳运动可提高老年大鼠的学习记忆能力,可能与长期游泳运动有效调整中枢神经递质多巴胺的合成及增强大脑伏隔核nNOS的表达有关.     

骨形态计量学观察睾酮对雄性去势大鼠皮质骨的影响

目的通过骨形态计量方法观察雄激素替代疗法对去睾丸大鼠皮质骨代谢的影响。方法30只4月龄SD雄性大鼠,随机分成基础对照组(A组、实验开始时处死),年龄对照组(B组)、去睾丸组(C组)和去睾丸加睾丸酮组(D组),B组和C组生理盐水5ml·kg-1·d-1,D组甲基睾丸酮片1.8mg·kg-1·d-1,灌胃90d。实验结束,处死全部大鼠,取胫骨中段进行不脱钙骨制片,用计算机全自动图象分析系统进行骨组织形态计量学分析。结果去睾丸后皮质骨静态参数如截面总面积、髓腔面积等无明显变化,动态参数骨外膜骨形成降低(P<0.05),内膜骨形成和吸收均有增加趋势。睾酮则使去睾丸大鼠皮质骨的静态参数有增加趋势,促使骨外膜形成增加,减少内膜骨吸收(P<0.05),对内膜骨形成影响不大。结论睾酮补充治疗短期内能对抗去睾丸引起的大鼠皮质骨内外膜的代谢变化,维持正常的皮质骨结构。     

睾丸酮对雄性大鼠类固醇性骨质疏松的影响

目的探讨睾丸酮对雄性大鼠类固醇性骨质疏松的影响。方法30只3月龄雄性SD大鼠,随机分成对照组(A组)、泼尼松组(B组)、睾丸酮(C组)。A组灌生理盐水(4mL·kg-1·d-1),B组予醋酸泼尼松灌胃(4mg·kg-1·d-1),C组灌胃给予甲睾酮(0.2mg·kg-1·d-1)+醋酸泼尼松(4mg·kg-1·d-1),共90d。实验结束后,处死全部大鼠取腰椎和胫骨上段进行不脱钙骨包埋切片,应用计算机自动图像分析系统进行骨组织形态计量学分析。结果与泼尼松组比较,胫骨上端松质骨的%Tb.Ar增加了108%(P<0.01),Tb.N增加了96%(P<0.05),Tb.Sp减少60%;BFR/TV增加了172%(P<0.05),Oc.N减少40.7%(P<0.05);腰椎松质骨的%Tb.Ar增加了52.4%(P<0.05),Tb.Th增加了42%(P<0.05),Tb.Sp减少20%(P<0.05),MAR增加26%(P<0.05)。结论睾丸酮可以有效阻止泼尼松所引起的骨骨质丢失,维持正常的骨质结构。     

衰老大鼠心肌细胞器形态的定性定量改变及其调控钙离子能力分析

目的　探讨心肌衰老机制。　方法　采用 Wistar大鼠 ,分老龄组 (2 2月龄 )和成年组 (7月龄 )。用透射电镜观察心肌细胞器形态定性改变 ;用体视学方法测定心肌细胞器形态定量改变 ;用 X射线能谱仪分析心肌细胞器调控 Ca2 +能力。　结果　与成年组比较 ,老龄组大鼠心肌改变 :(1)核有切痕、肌原纤维不规整、闰盘离解、线粒体和肌浆网肿胀、脂褐素和残余体增多。(2 )在心肌组织内 ,非肌细胞所占体积份数增加 ,线粒体和肌浆网体密度减少 ,线粒体外膜比面积、内膜 +嵴比面积、肌浆网比面积减少。(3)在舒张状态下 ,肌原纤维和线粒体内 Ca2 +增加 ,肌浆网内 Ca2 +减少。　结论　衰老心肌的舒缩力减退 ,心肌细胞器形态呈明显改变 ,心肌衰老与线粒体和肌浆网的形态改变及其调控 Ca2 +能力有直接关系。     

基于AMPK/ULK1通路探讨鸢尾素对老年糖尿病肌少症大鼠肌保护作用及机制

目的 探讨鸢尾素调节AMPK/ULK1通路对老年糖尿病大鼠肌保护的作用及机制。方法随机选择10只大鼠作为对照组（CON组），40只大鼠通过链脲佐菌素（STZ）注射构建2型糖尿病（T2DM）模型。将造模成功的大鼠随机均分为模型组（Mod组）、鸢尾素组（30μg/kg）、Compound C组（0.2 mg/kg）、鸢尾素+Compound C组（30μg/kg+0.2 mg/kg），每组10只，每天一次给药，连续治疗4周。CON组和Mod组给予等量生理盐水注射。抓绳实验检测大鼠肢体肌肉力量；称量大鼠体重、腓肠肌重量，计算腓肠肌重量占体重百分比（腓/体）；用血糖仪检测血糖水平；双抗体夹心法检测血清胰岛素水平；苏木精-伊红（HE）染色检测腓肠肌病理变化；Western blot检测自噬蛋白、AMPK/ULK1通路蛋白表达。结果 CON组大鼠肌细胞排列有序，无水肿坏死现象；Mod组大鼠肌细胞排列杂乱，出现细胞水肿、坏死以及炎性浸润现象，同时部分肌纤维出现溶解现象；鸢尾素组改善了以上现象，与CON组结构类似；Compound C组大鼠肌细胞水肿、坏死、炎性浸润现象加重，鸢尾素+Compound ...     

A Note on the Asymptotic Properties of Affected-sib-pair Linkage Tests

This article concerns the asymptotic properties of linkage tests for affected‐sib‐pair data under the null hypothesis of no linkage. We consider a popular single‐locus analysis model where the unknown parameters are the disease allele frequency, the three penetrances for the three genotypes at the disease locus, and the recombination fraction between the marker locus and the disease locus. These parameters are completely confounded under the null hypothesis of no linkage. We show that 1) If the total variance of the trait (i.e., the additive variance plus the dominance variance) is “separated” from 0, then the likelihood ratio statistic has an asymptotic 0.5χ²₀+ 0.5χ²₁ distribution; 2) If the prevalence of the trait is “separated” from 0 and the recombination fraction is fixed at 0, then the likelihood ratio statistic has an asymptotic distribution which is a mixture of χ²₀, χ²₁ and χ²₂ . The implications of these results are discussed.     

定性资料统计分析错误辨析与释疑

通过揭示大量的生物医学科研中出现的定性资料统计分析方面的错误案例,说明重视识别定性资料列联表的类型、检查前提条件和考虑统计分析目的,对于合理选用定性资料统计分析方法是至关重要的。     

运动-组胺激发试验对提高支气管哮喘诊断价值的研究

目的　探讨运动 -组胺激发试验 (EHIA)对支气管哮喘的诊断价值 .方法　对 2 0例健康者、118例支气管哮喘、2 2例过敏性鼻炎、2 4例慢性支气管炎患者进行运动 -组胺激发试验 ,并与单纯运动激发试验及组胺激发试验进行比较 .结果　显示运动 -组胺激发试验对哮喘患者的诊断阳性率达 97.4%、特异性 10 0 % ,且EHIA阳性所吸入的组胺量也反映了哮喘患者非特异性气道高反应性 .结论　运动 -组胺激发试验对提高早期及非典型支气管哮喘的确诊具有实用价值     

Performance of point-of care molecular and antigen-based tests for SARS-CoV-2: a living systematic review and meta-analysis

BackgroundMolecular and antigen point-of-care tests (POCTs) have augmented our ability to rapidly identify and manage SARS-CoV-2 infection. However, their clinical performance varies among individual studies.ObjectivesThe evaluation of the performance of molecular and antigen-based POCTs in confirmed, suspected, or probable COVID-19 cases compared with that of laboratory-based RT-PCR in real-life settings.Data sourcesMEDLINE/PubMed, Scopus, Embase, Web of Science, Cochrane Library, Cochrane COVID-19 study register, and COVID-19 Living Evidence Database from the University of Bern.Study eligibility criteriaPeer-reviewed or preprint observational studies or randomized controlled trials that evaluated any type of commercially available antigen and/or molecular POCTs for SARS-CoV-2, including multiplex PCR panels, approved by the United States Food and Drug Administration, with Emergency Use Authorization, and/or marked with Conformitè Europëenne from European Commission/European Union.ParticipantsClose contacts and/or patients with symptomatic and/or asymptomatic confirmed, suspected, or probable COVID-19 infection of any age.Test/sMolecular and/or antigen-based SARS-CoV-2 POCTs.Reference standardLaboratory-based SARS-CoV-2 RT-PCR.Assessment of risk of biasEligible studies were subjected to quality-control and risk-of-bias assessment using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.Methods of data synthesisSummary sensitivities and specificities with their 95% CIs were estimated using a bivariate model. Subgroup analysis was performed when at least three studies informed the outcome.ResultsA total of 123 eligible publications (97 and 26 studies assessing antigen-based and molecular POCTs, respectively) were retrieved from 4674 initial records. The pooled sensitivity and specificity for 13 molecular-based POCTs were 92.8% (95% CI, 88.9–95.4%) and 97.6% (95% CI, 96.6–98.3%), respectively. The sensitivity of antigen-based POCTs pooled from 138 individual evaluations was considerably lower than that of molecular POCTs; the pooled sensitivity and specificity rates were 70.6% (95% CI, 67.2–73.8%) and 98.9% (95% CI, 98.5–99.2%), respectively.DiscussionFurther studies are needed to evaluate the performance of molecular and antigen-based POCTs in underrepresented patient subgroups and different respiratory samples.     

Hemodynamic Reactivity to Laboratory Stressors in Healthy Subjects: Influence of Gender and Family History of Cardiovascular Diseases

Although laboratory stressor tests have been applied as a preliminary protocol in some cardiovascular studies, there is a lack of data comparing the pressor and chronotropic responses among the main stressor tests. Therefore, the aim of this study was to evaluate the variability in hemodynamic responsiveness to the main stressor tests, establish a hyperresponsiveness cutoff criterion and analyze the influence of gender and family history of cardiovascular diseases (CVDs) in healthy subjects. We examined hemodynamic responses to physical (cold pressor and handgrip tests) and mental (Stroop color-word test) stressors in 98 subjects (48 males and 50 females) without CVDs. All stressor tests resulted in increased blood pressure (BP) levels, which were lower and less dispersed in the handgrip test compared to the cold pressor test. Adopting the 75^th percentile as the cutoff in our data, we classified subjects exhibiting absolute pressor changes equal to or higher than 14, 24 and 36 mmHg in systolic and 9, 13 and 24 mmHg in diastolic BP during the handgrip, Stroop and cold pressor test, respectively, as hyperresponsives. Males exhibited greater (p<0.05) increases in systolic BP in the handgrip (11% vs. 8%) and cold pressor (25% vs. 21%) tests and in diastolic BP in the handgrip (12% vs. 7%) and Stroop (22% vs. 19%) tests than females. A positive association between family history of CVDs and pressor hyperreactivity to stressor tests was observed. We propose using the 75^th percentile of hemodynamic sample values as a cutoff criterion to classify individuals as pressor or chronotropic hyperreactives. We conclude that hemodynamic responsiveness to stressor tests in healthy subjects is positively influenced by male gender and family history of CVDs.     

羟基磷灰石涂层钛合金材料生物相容性研究初探

目的探讨一种新型的代骨材料--羟基磷灰石涂层的钛合金材料的生物相容性。方法制备羟基磷灰石涂层钛合金材料浸提液后,采用细胞毒性实验以观察实验样品浸提液对L929小鼠成纤维细胞的毒性反应;通过对小鼠尾静脉及腹腔注射试验样品浸提液后,观察其对小鼠的急性全身毒性反应;Ames实验及迟发型超敏反应实验对其遗传毒性及致敏性进行安全性评价。结果羟基磷灰石涂层钛合金材料浸提液对L929小鼠成纤维细胞的相对增殖率(RGR)为96.9%,细胞毒性反应为1级,无细胞毒性反应;对小鼠亦无明显的急性全身毒性作用,实验样品组与阴性对照组动物体质量差异无统计学意义(P0.05);遗传毒性Ames实验表明,在活化与非活化条件下,该材料浸提液对鼠伤寒沙门氏菌株的回变菌落数与对照组比均未增加2倍,对该菌株无诱变性;迟发型超敏反应实验显示,该材料浸提液无潜在的皮肤接触致敏性。结论羟基磷灰石涂层的钛合金材料具有良好的生物相容性。     

Diagnostic test allergens used for in vivo diagnosis of allergic diseases are at risk: a European Perspective

In the European Union (EU), allergens used for diagnostic tests (TAs) are defined as medicinal products and have to be registered by national authorities. The current situation is not homogeneous. Existing authorizations need to be kept in the market in some EU states, while others need complete new authorizations requiring clinical trials, quality assurance methods, stability studies, and periodic safety update reports. Allergen manufacturers argue that offering a comprehensive panel of TAs may be economically disastrous. Expenses for initiation and maintenance of TA authorizations far exceed their related revenues and manufacturers may be forced to significantly limit their allergen portfolios. The availability of a wide range of high‐quality TAs is very important for in vivo diagnoses of IgE‐mediated allergies. Increased regulatory demands induce costs that need to be covered by public health organizations or reimbursed by health insurance companies.     

国产微柱凝胶免疫检测试剂卡检测孕妇IgG血型抗体效价的实验研究

目的：比较微柱凝胶抗人球蛋白试验和传统试管抗人球蛋白试验检测O型孕妇血清中IgG抗-A和抗-B效价的差异,对国产微柱凝胶试剂卡检测孕妇IgG效价的决定值进行界定。方法：用国产微柱凝胶试剂卡和传统试管法平行检测524例丈夫为A型或B型的O型孕妇血清IgG抗-A和抗-B水平,经配对t检验、χ^2检验和回归分析,比较两种方法检测结果的差异并界定前者的决定值。结果：国产微柱凝胶试剂卡和传统试管法检测抗-A平均效价分别为249.98和120.85,抗-B为156.98和76.38,前一方法分别是后者2.07、2.06倍,差异均有显著性意义（t=19.64,P〈0.001;t=15.39,P〈0.001）;相关性分析得出两种方法测抗-A、抗-B效价均有高度的相关性,相关系数r分别是0.8857（t=30.76,P〈0.001）、0.8996（t=33.22,P〈0.001）,通过回归方程得出国产微柱凝胶试剂卡检测抗-A、抗-B效价的决定值分别为128、116;以IgG抗体效价≥64判为阳性,国产微柱凝胶试剂卡测抗-A、抗-B阳性率分别为73.66、52.29,明显高于传统试管法的47.33、34.35,均具有统计学意义（χ^2=69.00,P〈0.01;χ^2=47.00,P〈0.01）。结论：国产微柱凝胶试剂卡比传统试管法操作更简便、快捷,应用于孕妇产前IgG抗-A、抗-B效价检测比后者具有更高的灵敏度,对其决定值的界定,将为临床提供更可靠的诊断依据。