丙氨瑞林治疗子宫内膜癌病人的性激素及有丝分裂指数的变化

目的：观察丙氨瑞林对子宫内膜癌的治疗作用。方法：对诊刮确诊的１７例子宫内膜癌病人，予丙氨瑞林７００μｇ，ｉｍ，ｑｄ×７ｄ，用药前后作性激素测定及组织学检查。结果：绝经妇女用药后血中ＦＳＨ和ＬＨ下降（Ｐ＜０．０１和＜０．０５），雌二醇、孕酮及睾丸酮变化不明显。其中１３例内膜样腺癌用药后有丝分裂指数明显下降（Ｐ＜０．０１），有丝分裂指数变化与癌周内膜之反应有关。呈增生反应癌周内膜癌组织有丝分裂指数下降值明显高于呈萎缩状态癌周内膜。结论：丙氨瑞林治疗子宫内膜癌后能降低ＦＳＨ和ＬＨ水平，对子宫内膜癌尤其是雌激素依赖性内膜癌有一定疗效。     

Left ventricle haemodynamics and vaso-active hormones during graded supine exercise in healthy male subjects

Left ventricle systolic and diastolic functional parameters were measured by gated equilibrium radionuclide cardiography in 12 healthy men (age 33–51 years) at rest and during graded supine exercise. The leftventricle end-diastolic volume showed an initial small (11%) increase during low submaximal exercise [from mean 163 (SD 40) at rest to mean 181 (SD 48) ml], while left ventricle end-systolic volume decreased successively [from mean 59 (SD 19) to mean 39 (SD 21) ml] with increasing exercise. Stroke volume was therefore elevated at all exercise levels compared with rest [mean 104 (SD 23) ml], and the peak value [mean 128 (SD 33) ml] was found at the lowest exercise level, contributing 40% to the initial increase in cardiac output. Cardiac output increased from mean 6.2 (SD 1.4) at rest to mean 20.2 (SD 5.0) 1 · min^–1 at maximum. Left ventricle peak ejection and peak filling rates increased from mean 449 (SD 89) and mean 442 (SD 85) ml · s^–1 at rest to mean 996 (SD 227) and mean 1255 (SD 333) ml · s^–1, respectively, at maximum. The myocardium oxygen consumption, assumed to be proportional to the sum of the stroke work and the potential energy, increased fourfold, but absolute values were twice as high as expected, indicating that extrapolation from data obtained in dog hearts (as we have done) cannot be directly applied to humans. Selected vaso-active hormones were measured at all exercise intensities. Noradrenaline (NA), adrenaline (A) and angiotensin II (AII) concentrations showed a very pronounced increase at maximal exercise compared with the preceding lower intensites, while atrial natriuretic factor (ANF) and cyclic guanosinemonophosphate (cGMP) concentrations showed a more continuous increase, and dopamine (DA) remained almost unchanged. This speaks in favour of a crucial role for NA, A and AII in preserving blood pressure at maximum exercise, while DA probably has no importance for the cardiovascular homeostasis during exercise. Increases in concentrations of ANF and cGMP were highly correlated (r = 0.86). Our data supported the opinion that there is a cardiac limitation to maximal performance connected to the cardiac pumping capacity.     

Proteolytic Processing Mechanisms in the Biosynthesis of Neuroendocrine Peptides: The Subtilisin-like Proprotein Convertases

The recent discovery of a novel family of precursor processing endoproteases has greatly accelerated progress in understanding the complex mechanisms underlying the maturation of prohormones, neuropeptides, and many other precursor-derived proteins. At least six members of this family have been found thus far in mammalian species, several having alternatively spliced isoforms, and related enzymes have been identified in many invertebrates, including molluscs, insects, nematodes, and coelenterates. The proprotein convertases are all dependent on calcium for activity and all possess highly conserved subtilisin-like domains with the characteristic catalytic triad of this serine protease (ordered Asp, His, and Ser along the polypeptide chain). Two members of this family, PC2(SPC2) and PC1/PC3(SPC3), appear to play a preeminent role in neuroendocrine precursor processing. Both convertases are expressed only in the brain and in the extended neuroendocrine system, while another important family member—furin/PACE (SPC1)—is expressed more ubiquitously, in almost all tissues, and at high levels in liver. SPC2 and SPC3 exhibit acidic pH optima and other properties which enhance their activity in the acidic, calcium-enriched environment of the dense-core secretory granules of the regulated pathway in neuroendocrine cells, while furin has a neutral pH optimum and is localized predominantly to the trans Golgi network where it is retained by a C-terminal transmembrane domain. Furin processes a wide variety of precursors in the constitutive pathway, such as those of growth factors, receptors, coagulation factors, and viral glycoproteins. Recent findings on the processing of proopiomelanocortin, proinsulin, proglucagon, and several other neuroendocrine precursors by SPC2 and SPC3 are discussed, along with information on the structure, properties, evolution, developmental expression, and regulation or the convertases. An inherited defect in the fat/fat mouse which affects the processing of proinsulin, and probably also many other prohormones, due to a point mutation in carboxypeptidase E has recently been identified and has begun to provide new insights into the functional integration of the individual processing steps.     

男性胆囊结石患者血清性激素和前列腺素改变的探讨

借助RIA,对28例胆囊结石男性(平均57.5岁)及26名健康中、老年男性(平均63.3岁)进行了血清雌二醇(E_2)、孕酮、睾酮和前列腺素类(PGs)检测,以探索胆石形成机理。结果,1)在胆石男病人中.平均E_2和平均孕酮水平均高,他们的平均睾酮则低下,与健康对照男性相应诸值比较,差异非常显著或显著(P<0.001,0.05,0.05);2)至于平均PGs,胆石男性组者与健康对照男性相比,前者也相当高(23.01pg/ml对16.31pg/ml),只是两组间差异尚无统计学意义。作者等初步设想,胆石男性小,如同胆石女性那般,本症也可能是某种垂体性腺激素分泌紊乱性疾病。     

不同强度运动对女子游泳运动员性激素水平的影响及特点

本研究以放兔分析法观察不同强度运动前后19名女子游泳运动员血清促卵泡激素(FSH)、黄体生成素(LH)、雌二醇(E_2)、孕酮(P)、睾酮(T)及胰岛素(Ins)的变化。受试者在卵泡及黄体两期分别进行短时间高强度间歇运动——6×50m全速力竭性游泳和长时间持续运动——1000m全速力竭性游泳。在运动前5分钟及运动后即刻分别采集静脉血测定各种激素含量。主要结果如下:受试者从事6×50m最大速度间歇游泳后,卵泡期各种激素浓度的变化均显著高于运动前安静状态,黄体期变化不一,FSH、LH降低,E_2、P、T及Ins升高。从事1000m全速游泳后,激素变化表现为卵泡期FSH、LH、E_2、P均升高,T及Ins降低;黄体期E_2、P、T升高,Ins降低,FSH、LH无显著变化,两期相比黄体期运动成绩优于卵泡期。上述结果提示:①受试者月经周期的黄体期机体有氧能力强于卵泡期,运动能力的增强与黄体期E_2、P、T水平升高有关。②FSH、LH与E_2、P分泌变化并非同步一致,说明运动中E_2升高并非受制于促性腺激素,而主要是卵巢分泌量升高所致。③运动中E_2、P、T具有协同效应,可抵抗疲劳,提高人体运动能力。     

Construction of a risk model of steroid-induced necrosis of the femoral head and prediction of potential Chinese medicine treatments北大核心

背景:随着疾病治疗模式的改变,人们已经意识到中医药在激素性股骨头坏死治疗过程中的重要性,因此利用生物信息学从分子水平分析激素性股骨头坏死的发病机制,构建疾病风险模型,并预测具有潜在治疗作用的中药,为后期中医药治疗激素性股骨头坏死提供一定的理论依据。目的:基于生物信息学挖掘激素性股骨头坏死的竞争性内源RNA(ceRNA)调控网络,分析其在激素性股骨头坏死中的分子调控机制,预测相关疾病靶点并构建疾病风险模型,同时预测具有潜在治疗作用的中药。方法:检索GEO数据库,下载激素性股骨头坏死的矩阵文件GSE123568和基因注释文件GPL15207。借助R语言等软件分析得到差异表达的长链非编码RNA与mRNA,并通过公共数据库预测与差异表达长链非编码RNA关联的miRNA-mRNA,再将预测到的mRNA与差异表达mRNA取交集,整合得到ceRNA网络。随后采用STRING数据库和Cytoscape软件筛选关键基因,利用R语言分析关键基因的功能与相关通路,并挖掘关键ceRNA网络。最后根据关键基因构建激素性股骨头坏死的风险模型,并进行中药预测。结果与结论:(1)与健康对照相比,激素性股骨头坏死患者共有7个长链非编码RNA和1763个mRNAs存在差异表达;(2)筛选出STAT3、KAT2B、AGO4、JAK2、JAK1、PTGS2共6个关键基因;(3)关键基因所富集的功能包括对肽激素的反应、白细胞介素6介导的信号通路、细胞对白细胞介素6的反应等生物学过程,涉及JAK-STAT、脂肪细胞因子、催乳素等信号通路;(4)4种mi RNAs(mi R-135a-5p、mi R-137、mi R-17-5p、miR-20b-5p)和2种长链非编码RNA(SNHG11、C20orf197)可能在导致激素性股骨头坏死发生发展过程中发挥关键作用;(5)KAT2B最有可能是激素性股骨头坏死发生发展的风险因子;(6)郁金、淫羊藿、黄芪具备治疗激素性股骨头坏死疾病靶点的可能。通过对激素性股骨头坏死相关长链非编码RNA介导的ceRNA网络进行分析,识别出潜在的疾病靶点、信号通路及潜在治疗中药,为进一步阐明其发病机制,并为后续的实验研究提供参考依据。     

Thymus Ontogeny in Frogs: T-Cell Renewal at Metamorphosis

Metamorphosis in amphibians presents a unique problem for the developing immune system. Because tadpoles are free-living, they need an immune system to protect against potential pathogens. However, at metamorphosis, they acquire a variety of new adultspecific molecules to which the tadpole immune system must become tolerant. We hypothesized that Xenopus laevis tadpoles may avoid potentially destructive antiself responses by largely discarding the larval immune system at metamorphosis and acquiring a new one. By implanting triploid (3N) thymuses into diploid (2N) hosts, we examined the influx and expansion of host T-cell precursors in the donor thymus of normally metamorphosing and metamorphosis-inhibited frogs. We observed that donor thymocytes are replaced by host-derived cells during metamorphosis, but inhibition of metamorphosis does not prevent this exchange of cells. The implanted thymuses export T cells to the spleen. This donor-derived pool of cells declines after metamorphosis in normally developing frogs but is retained to a greater extent if metamorphosis is inhibited. These studies confirm previous observations of a metamorphosis-associated wave of expansion of T cells and demonstrate that it is not dependent on the relatively high concentrations of thyroid hormones required for metamorphosis. Although some larval T cells persist through metamorphosis, others may be destroyed or the larval population is significantly diluted by the expanding adult population.     

重症SIRS患者的正常甲状腺病态综合征

目的：探索全身炎症反应综合征（SIRS）患者的正常甲状腺病态综合征（ESS）的发生规律。 方法： 测定50例SIRS病人的总三碘甲状腺原氨酸（TT3）、总四碘甲状腺原氨酸（TT4）、游离三碘甲状腺原氨酸（FT3）、游离四碘甲状腺原氨酸（FT4）、促甲状腺素（TSH），并根据是否多脏器功能障碍综合征（MODS）分组。计算急性生理和慢性健康评估Ⅱ（APACHEⅡ）评分，记录病人转归以及从发病到检测的时间（患病时间）。 结果： TT3或FT3降低的45例。TT3与APACHEⅡ评分呈对数负相关（r＝－0.330，P<0.05）,TT3/TT4与患病时间呈对数负相关（r=－0.316, P<0.05）。MODS组的TT3、TT4、FT3水平显著低于无MODS组（P<0.05）。 结论： SIRS和MODS病人发生低T3、低T4可能性大，反映炎症反应对甲状腺轴的影响，随着病情加重、患病时间延长，影响进一步深化。