基于PERK-eIF2α-CHOP通路调控巨噬细胞胆固醇稳态及冠心康含药血清干预机制研究＊

目的 观察具有益气化痰活血作用的冠心康对人单核/巨噬细胞株THP-1细胞PERK-eIF2α信号通路及相关活化转录因子（ATF）和C/EBP同源转录因子（CHOP）的影响，探究冠心康对胆固醇在巨噬细胞内质网中的代谢稳态调节及作为“脂毒”流出后异常沉积的相关作用。方法 采用100 ng·mL^-1 PMA及80 μg·mL^-1氧化低密度脂蛋白诱导THP-1细胞株，构建巨噬细胞模型，并随机分为模型组、冠心康组、辛伐他汀组、正常组。分别采用10%小牛血清及含药血清干预模型细胞72 h后收集细胞。HE染色观察巨噬细胞病理形态变化，同时进行胆固醇及脂滴含量测定。分别采用Real-time PCR及Western blot法检测各组细胞PERK、eIF2α、ATF、CHOP mRNA及蛋白的表达。结果 HE染色观察到模型组细胞内呈现较多红色脂滴，经胆固醇含量测定，明显高于正常组，脂滴含量测定与前者一致（P<0.01）。模型组细胞ATF、CHOP基因表达水平均显著升高（P<0.01）。与模型组比较，冠心康组和辛伐他汀组细胞ATF、CHOP基因表达水平均显著降低（P<0.01）。PERK磷酸化以及CHOP蛋白表达水平在冠心康和辛伐他汀干预组表现为显著下调，与模型组比较，差异具有统计学意义（P<0.05）。结论 冠心康可能通过调控PERK-eIF2α-CHOP通路相关基因及蛋白，减少泡沫细胞形成，从而减轻内质网应激，维持细胞内胆固醇稳态，减少细胞内胆固醇沉积。     

Special issue “The advance of solid tumor research in China”: Multi-omics analysis based on 1311 clear cell renal cell carcinoma samples identifies a glycolysis signature associated with prognosis and treatment response

In clear cell renal cell carcinoma (ccRCC), glycolysis is enhanced mainly because of the increased expression of key enzymes in glycolysis. Hence, the discovery of new molecular biomarkers for glycolysis may help guide and establish a precise system of diagnosis and treatment for ccRCC. Expression profiles of 1079 tumor samples of ccRCC patients (including 311 patients treated with everolimus or nivolumab) were downloaded from public databases. Proteomic profiles of 232 ccRCC samples were obtained from Fudan University Shanghai Cancer Center (FUSCC). Biological changes, tumor microenvironment and prognostic differences were explored between samples with various glycolysis characteristics. There were significant differences in CD8⁺ effector T cells, epithelial-to-mesenchymal transition and pan-fibroblast TGFb between the Low and High glyScore groups. The tumor mutation burden of the Low glyScore group was lower than that of the High glyScore group. And higher glyScore was significantly associated with worse overall survival (OS) in 768 ccRCC patients (P < .0001). External validation in FUSCC cohort also indicated that glyScore was of strong ability for predicting OS (P < .05). GlyScore may serve as a biomarker for predicting everolimus response in ccRCC patients due to its significant associations with progression-free survival (PFS). And glyScore may also predict overall survival in patients treated with nivolumab. We calculated the glyScore in ccRCC and the defined glyScore was of strong ability for predicting OS. In addition, glyScore may also serve as a biomarker for predicting PFS in patients treated with everolimus and could predict OS in patients treated with nivolumab.     

定量分析对常规超声联合超声造影定性误诊甲状腺结节的诊断价值

摘要：目的：探讨超声造影（CEUS）定量分析对常规超声联合CEUS定性诊断误诊为恶性的甲状腺结节与甲状腺乳头状癌的鉴别诊断价值。方法：选取2018年7月至2021年11月在我院超声科行甲状腺常规超声及CEUS检查，术前联合超声诊断为恶性（C-TIRADS≥4b 或 CEUS 表现为低增强和快速消退任一征像）而病理为良性的35位患者共35个结节为研究组；选择同期联合超声诊断与病理一致的甲状腺乳头状癌患者47例做为对照组。分析常规超声及CEUS特征，并将结节整体、中央部、边缘部及邻近正常甲状腺实质作为感兴趣区分别绘制时间-强度曲线（TIC）进行定量分析，比较两组结节各定量参数之间的差异。结果：研究组整体相对上升时间（△RT）以0.45为截断值，诊断恶性结节的敏感度为97.9%，特异度为85.7%，受试者工作（ROC）曲线下面积为0.96；研究组中央区△RT以0.55为截断值，诊断恶性结节的敏感度为95.7%，特异度为82.9%，ROC曲线下面积为0.87；研究组边缘区△RT以0.25为截断值，诊断恶性结节的敏感度为89.4%，特异度为77.1%，ROC曲线下面积为0.89。结论：CEUS定量分析在常规超声联合CEUS定性误诊甲状腺结节的诊断中具有一定的鉴别诊断价值。     

Effects of Angiotensin II Receptor Blockers on Ventricular Hypertrophy in Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Cardiovascular Drugs and Therapy - Animal studies have suggested that angiotensin II receptor blockers (ARBs) can attenuate or reverse the progression of hypertrophic cardiomyopathy, while clinical...     

Opposing patterns in self-reported and measured physical activity levels in middle-aged adults

Physical activity brings significant health benefits to middle-aged adults, although the research to date has been focused on late adulthood. This study aims to examine how ageing affects the self-reported and accelerometer-derived measures of physical activity levels in middle-aged adults. We employed the data recorded in the UK Biobank and analysed the physical activity levels of 2,998 participants (1381 men and 1617 women), based on self-completion questionnaire and accelerometry measurement of physical activity. We also assessed the musculoskeletal health of the participants using the dual-energy X-ray absorptiometry (DXA) measurements provided by the UK Biobank. Participants were categorised into three groups according to their age: group I younger middle-aged (40 to 49 years), group II older middle-aged (50 to 59 years), and group III oldest middle-aged (60 to 69 years). Self-reported physical activity level increased with age and was the highest in group III, followed by group II and I (P?<?0.05). On the contrary, physical activity measured by accelerometry decreased significantly with age from group I to III (P?<?0.05), and the same pertained to the measurements of musculoskeletal health (P?<?0.05). It was also shown that middle-aged adults mostly engaged in low and moderate intensity activities. The opposing trends of the self-reported and measured physical activity levels may suggest that middle-aged adults over-report their activity level as they age. They should be aware of the difference between their perceived and actual physical activity levels, and objective measures would be useful to prevent the decline in musculoskeletal health.