硫酸锌对心肌慢反应电活动和哇巴因引起振荡后电位的影响

本文目的旨在观察硫酸锌对心肌慢反应电活动的影响,所得结果如下:(1) 0.1～0.3mmol硫酸锌能使高钾除极引起的豚鼠乳头肌慢反应动作电位APA和V_max降低,APD₅₀和APD₉₀)显著延长;(2) 0.1～0.3 mmol硫酸锌能抑制家兔离体窦房结细胞的自律性,使窦房结APA降低,APD₉₀延长,SP₀和SP₄减小;(3) 0.1 mmol硫酸锌可对抗0.4μmol哇巴因诱发的豚鼠心室肌振荡后电位,提高引起振荡后电位的哇巴因阈浓度。提示:锌抑制心肌慢反应电活动。     

楤木根皮中皂甙化学成分的研究

楤木根皮中的主要成分是皂甙。将总皂甙以柱层析分离,得到三个化合物(Ⅰ～Ⅲ),经光谱分析和化学方法证明,Ⅰ为楤木皂甙A(araloside A);Ⅱ为银莲花甙(narcissiflorine);Ⅲ是3-O-[β-D-吡喃葡萄糖-(1→2)-β-D-吡喃木糖-(1→)2)-α-L-阿拉伯糖]-齐墩果酸。Ⅲ为一新皂甙,命名为楤木皂甙D(araloside D)。     

清热中药对大鼠下丘脑组织AVP含量的影响

目的：清热中药大多具有一定的解热作用,为探讨其解热作用机理,我们选用典型的清热中药黄芩,银花,连翘组成清热方,从体温调节中枢神经介质方面来研究其解热作用机制。方法;选用Ｗｉｓｔａｒ大鼠,按体重随机分作３组,背部皮下注射酵母混悬液制造发热模型,给药组灌服清热方颗粒剂,模型组予等量饮用水,正常对照组不作处理,给药２ｈ后断头取脑,用放免方法检测大鼠下丘脑组织中ＡＶＰ含量。结果：模型组大鼠体温和下丘脑组织     

A comparison of DNA sequencing and gene expression profiling to assist tissue of origin diagnosis in cancer of unknown primary

Cancer of unknown primary (CUP) is a syndrome defined by clinical absence of a primary cancer after standardised investigations. Gene expression profiling (GEP) and DNA sequencing have been used to predict primary tissue of origin (TOO) in CUP and find molecularly guided treatments; however, a detailed comparison of the diagnostic yield from these two tests has not been described. Here, we compared the diagnostic utility of RNA and DNA tests in 215 CUP patients (82% received both tests) in a prospective Australian study. Based on retrospective assessment of clinicopathological data, 77% (166/215) of CUPs had insufficient evidence to support TOO diagnosis (clinicopathology unresolved). The remainder had either a latent primary diagnosis (10%) or clinicopathological evidence to support a likely TOO diagnosis (13%) (clinicopathology resolved). We applied a microarray (CUPGuide) or custom NanoString 18-class GEP test to 191 CUPs with an accuracy of 91.5% in known metastatic cancers for high–medium confidence predictions. Classification performance was similar in clinicopathology-resolved CUPs – 80% had high–medium predictions and 94% were concordant with pathology. Notably, only 56% of the clinicopathology-unresolved CUPs had high–medium confidence GEP predictions. Diagnostic DNA features were interrogated in 201 CUP tumours guided by the cancer type specificity of mutations observed across 22 cancer types from the AACR Project GENIE database (77,058 tumours) as well as mutational signatures (e.g. smoking). Among the clinicopathology-unresolved CUPs, mutations and mutational signatures provided additional diagnostic evidence in 31% of cases. GEP classification was useful in only 13% of cases and oncoviral detection in 4%. Among CUPs where genomics informed TOO, lung and biliary cancers were the most frequently identified types, while kidney tumours were another identifiable subset. In conclusion, DNA and RNA profiling supported an unconfirmed TOO diagnosis in one-third of CUPs otherwise unresolved by clinicopathology assessment alone. DNA mutation profiling was the more diagnostically informative assay. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.     

Testing for associations between HbA1c levels,polygenic risk and brain health in UK Biobank (N = 39 283)

Aim

To investigate whether continuous HbA1c levels and HbA1c-polygenic risk scores (HbA1c-PRS) are significantly associated with worse brain health independent of type 2 diabetes (T2D) diagnosis (vs. not), by examining brain structure and cognitive test score phenotypes.

Methods

Using UK Biobank data (n = 39 283), we tested whether HbA1c levels and/or HbA1c-PRS were associated with cognitive test scores and brain imaging phenotypes. We adjusted for confounders of age, sex, Townsend deprivation score, level of education, genotyping chip, eight genetic principal components, smoking, alcohol intake frequency, cholesterol medication, body mass index, T2D and apolipoprotein (APOE) e4 dosage.

Results

We found an association between higher HbA1c levels and poorer performance on symbol digit substitution scores (standardized beta [β] = −0.022, P = .001) in the fully adjusted model. We also found an association between higher HbA1c levels and worse brain MRI phenotypes of grey matter (GM; fully-adjusted β = −0.026, P < .001), whole brain volume (β = −0.072, P = .0113) and a general factor of frontal lobe GM (β = −0.022, P < .001) in partially and fully adjusted models. HbA1c-PRS were significantly associated with GM volume in the fully adjusted model (β = −0.010, P = .0113); however, when adjusted for HbA1c levels, the association was not significant.

Conclusions

Our findings suggest that measured HbA1c is associated with poorer cognitive health, and that HbA1c-PRS do not add significant information to this.