脊髓小脑共济失调2型家系ATXN2基因中间重复病例表型与分子遗传学特征

目的探讨脊髓小脑共济失调2型(SCA2)致病基因ATXN2异常等位基因中间重复个体的表型和分子遗传学特点。方法针对2005—2018年中日友好医院神经科运动障碍与神经遗传病研究中心收集的1383个常染色体显性遗传共济失调家系的先证者和部分家系成员,采用荧光标记毛细管电泳片段分析方法进行动态突变检测,对携带ATXN2基因中间重复的个体进行临床表型和遗传特征分析。结果共检出163个家系(包含先证者和家系成员共203人)携带异常扩展的ATXN2基因CAG重复序列,其中93个家系中有107例的异常扩展等位基因重复次数在29~34次之间。在其中的20个亲子对中,父系遗传16个,异常等位基因的代间扩展增加0~28次,母系遗传4个,异常等位基因的代间扩展增加0~4次。结论对于临床拟诊SCA2家系患者,需对其亲代或成年子代个体进行ATXN2基因检测,以免漏诊。动态突变基因检测有助于识别中间重复的个体,对明确家系致病基因和遗传咨询至关重要。     

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

Pan-cancer proteomic map of 949 human cell lines

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Adherence to a Mediterranean Lifestyle and Changes in Frequency,Severity, and Localization of Pain in Older Adults

ObjectiveTo assess the association between adherence to a Mediterranean lifestyle and changes in pain, and its characteristics over time in older adults.Patients and MethodsWe analyzed data from 864 and 862 community-dwelling individuals aged 65+ years from the Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain (Seniors-ENRICA) Seniors-ENRICA-1 (2008–2010 to 2012) and Seniors-ENRICA-2 (2015–2017 to 2019) cohorts, with a median follow-up of 2.8 and 2.4 years, respectively. Adherence to a Mediterranean lifestyle was assessed at baseline with the 27-item Mediterranean lifestyle (MEDLIFE) index. Pain changes over time were calculated with a pain scale that assessed the frequency, severity, and the number of pain locations both at baseline and follow-up. Multivariable-adjusted relative risk ratios (RRRs) were obtained using multinomial logistic regression.ResultsIn the pooled cohorts, after a median follow-up of 2.6 years, pain worsened for 697 participants, improved for 734, and did not change for 295. Compared with the lowest category of MEDLIFE adherence, those in the highest category showed an RRR of improvement vs worsening of overall pain of 1.85 (95% CI, 1.28 to 2.67; P-trend<.001). MEDLIFE adherence was also linked to improvement in pain frequency (RRR, 1.98; 95% CI, 1.31 to 3.01; P-trend=.001), pain severity (RRR, 2.00; 95% CI, 1.33 to 3.00; P-trend=.001), and a reduction in the number of pain locations (RRR, 1.68; 95% CI, 1.13 to 2.50; P-trend=.004). Limitations of this study are the use of self-reported lifestyle data.ConclusionA Mediterranean lifestyle was associated with improvement of pain characteristics in older adults. Experimental studies should assess the efficacy of an integral lifestyle approach for the management of pain in older adults.