Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin

1. Download : Download high-res image (241KB)
2. Download : Download full-size image

     

基于弥散张量成像的脑白质微结构分析方法在视路损伤中的应用进展

视觉通路包括视神经、视交叉、视束、视放射及视皮质。常规磁共振检查技术难以发现视路损伤后白质纤维微结构改变,眼科学检查也存在一定的局限性及主观性,且不能探测后视路的变化。弥散张量成像(diffusion tensor imaging,DTI)作为一种新兴的磁共振成像技术,通过各种后处理分析方法结合不同的参数进行分析,可提供组织的微结构信息,并能够直观显示活体白质纤维束,在无创地探索疾病的神经病理机制、评估预后方面起着重要的作用。近年来随着DTI后处理方法的不断创新,其在视路损伤中的研究越来越多。本文在介绍DTI的主要参数及常见脑白质微结构分析方法的同时,阐述了其在视路损伤研究中的应用,并进一步对各种分析方法的优缺点进行总结。     

How effective has the Spanish lockdown been to battle COVID-19? A spatial analysis of the coronavirus propagation across provinces

This paper examines the propagation of COVID-19 across the Spanish provinces and assesses the effectiveness of the Spanish lockdown of the population implemented on March 14, 2020 in order to battle this pandemic. To achieve these objectives, a standard spatial econometric model used in economics is adapted to resemble the popular reproduction models employed in the epidemiological literature. In addition, we introduce a counterfactual exercise that allows us to examine the Gross domestic product (GDP) gains of bringing forward the date of the Spanish Lockdown. We find that the number of COVID-19 cases would have been reduced by 70.4% in the absence of spatial propagation between the Spanish provinces. We also determine that the lockdown prevented the propagation of the virus within and between provinces. As such, the Spanish lockdown reduced the number of potential COVID-19 cases by 82.8%. However, the number of coronavirus cases would have been reduced by an additional 11.6% if the lockdown had been brought forward to March 7, 2020. Finally, an earlier lockdown would have saved approximately 26,900,000,000 euros.     

Germline variant burden in multidrug resistance transporters is a therapy-specific predictor of survival in breast cancer patients

Multidrug resistance due to facilitated drug efflux mediated by ATP-binding cassette (ABC) transporters is a main cause for failure of cancer therapy. Genetic polymorphisms in ABC genes affect the disposition of chemotherapeutics and constitute important biomarkers for therapeutic response and toxicity. Here we correlated germline variability in ABC transporters with disease-specific survival (DSS) in 960 breast cancer (BRCA), 314 clear cell renal cell carcinoma and 325 hepatocellular carcinoma patients. We find that variant burden in ABCC1 is a strong predictor of DSS in BRCA patients, whereas candidate polymorphisms are not associated with DSS. This association is highly drug-specific for subgroups treated with the MRP1 substrates cyclophosphamide (log-rank p = 0.0011) and doxorubicin (log-rank p = 0.0088) independent of age and tumor stage, whereas no association was found in individuals treated with tamoxifen (log-rank p = 0.13). Structural mapping of significant variants revealed multiple variants at residues involved in protein stability, cofactor stabilization or substrate binding. Our results demonstrate that BRCA patients with high variant burden in ABCC1 are less prone to respond appropriately to pharmacological therapy with MRP1 substrates, thus incentivizing the consideration of genomic germline data for precision cancer medicine.     

耳穴贴压联合涌泉穴按摩对老年原发性高血压患者血压变异性的影响

目的:探讨耳穴贴压联合涌泉穴按摩治疗老年原发性高血压的效果及对患者血压变异性(BPV)的影响。方法:将94例老年原发性高血压患者随机分为对照组(n=47)和观察组(n=47)。常规西医治疗基础上,观察组给予王不留行籽耳穴贴压联合涌泉穴按摩治疗。比较两组治疗前后收缩压(SBP)、舒张压(DBP)水平、SBP/DBP下降幅度并评估降压疗效,BPV根据24 h动态血压监测结果评估,计算两组治疗前后24h SBP标准差(24h SBP)、24h DBP标准差(24h DBP)、白天SBP标准差(dSSD)、白天DBP标准差(dDSD)、夜间SBP标准差(nSSD)和夜间DBP标准差(nDSD),记录两组治疗期间不良反应情况。结果:观察组治疗后SBP、DBP水平和下降幅度均优于对照组(P<0.05); 观察组降压总有效率97.87%明显高于对照组82.98%,差异有统计学意义(P<0.05); 对照组治疗后24h SBP、24h DSD、dSSD、dDSD较治疗前有明显下降(P<0.05),观察组治疗后24h SBP、24h DSD、dSSD、dDSD、nSSD显著低于治疗前(P<0.05),观察组治疗后24h SBP、24h DSD、dSSD均显著低于对照组,差异有统计学意义(P<0.05); 两组不良反应以头晕、头痛、恶心和眩晕为主,症状程度均较轻,患者耐受性好,组间不良反应率比较差异均无统计学意义(P<0.05)。结论:常规西医治疗基础上给予中医耳穴贴压联合涌泉穴按摩,不仅能有效降低老年原发性高血压患者血压水平和增益降压疗效,而且能显著降低BPV。     

The effect of level of injury and physical activity on heart rate variability following spinal cord injury

Objective/Background: To assess frequency domain heart rate variability (HRV) parameters at rest and in response to postural autonomic provocations in individuals with spinal cord injury (SCI) and investigate the autonomic influences on the heart of different physical activities.

Design: Cross-sectional study.

Methods: Ten subjects with complete cervical SCI and fourteen subjects with complete low thoracic SCI were prospectively recruited from the community and further divided in sedentary and physically active groups, the latter defined as regular weekly 4 hour physical activity for the preceding 3 months. Sixteen healthy individuals matched for sex and age were recruited to participate in the control group. The Low Frequency (LF), High Frequency (HF) powers and the LF/HF ratio of HRV were measured from continuous electrocardiogram (ECG) recordings at rest and after sitting using a fast Fourier transformation.

Outcome measures: The LF,HF, and the LF/HF ratio at rest and after sitting.

Results: A significant decrease in all HRV parameters in patients with SCI was found compared to controls. The change in HF, LF and LF/HF following sitting maneuver was significantly greater in controls as compared with the SCI group and greater in subjects with paraplegia as compared to subjects with tetraplegia. Better HRV values and enhanced vagal activity appears to be related to the type of physical activity in active subjects with paraplegia.

Conclusion: In this cohort of subjects spectral parameters of HRV were associated with the level of the injury. Passive standing was associated with higher HRV values in subjects with paraplegia.     

Agreement between blood draw techniques for assessing platelet activation by flow cytometry

It is widely believed that assays of platelet activation are susceptible to preanalytical variables related to blood draw technique. We assessed platelet activation by whole blood flow cytometry and investigated the effects of: (1) drawing blood into vacuum tubes or manually aspirated syringes, and (2) discarding the first drawn blood sample (discard tube). Platelet P-selectin expression and platelet-monocyte complexes were measured by flow cytometry under both basal conditions and following stimulation with 0.1, 1, or 10 µM ADP. Bland-Altman plots demonstrated agreement between results for vacuum tube and syringe-aspirated samples with an a priori-defined clinically relevant agreement limit of 5%. Agreement of results was also observed between discard tube and second draw samples for both vacuum-driven and manually aspirated blood. We conclude that a vacuum tube or a manually-aspirated syringe can be used when assessing platelet activation by flow cytometry and that there is no need for a discard tube.