紫檀芪调控KDR和EGFR活性发挥抗肾细胞癌作用研究

目的 利用网络药理学对紫檀芪抗肾细胞癌潜在靶点进行预测,探讨其多靶点、多通路机制抗肾透明细胞癌的分子机制.方法 利用TCMSP、Swiss Target Prediction、Chembl数据库预测紫檀芪的作用靶点,利用OMIM、DisGeNET数据库获得肾细胞癌相关靶点蛋白,对两者靶点进行交集,并用JVENN绘制Venn图,利用STRING及Cytoscape构建PPI网络,根据degree值筛选出关键蛋白,利用GEPIA数据库分析关键蛋白在肾癌细胞及配对正常肾细胞中的差异表达,并利用分子对接对紫檀芪与关键蛋白相关作用进行验证.结果 紫檀芪的潜在靶点有614个,肾透明细胞癌的相关靶点有280个,两者共同作用的靶点有33个,关键的靶点包括MAPK1、EGFR、AKT1、PIK3CB、KDR,其中KDR和EGFR在肾细胞癌中表达显著高于正常配对的肾组织.分子对接发现紫檀芪与KDR和EGFR均具有较好的结合能力.结论 紫檀芪抗肾细胞癌具有多靶点、多途径的特点,KDR和EGFR可能为紫檀芪抗肾细胞癌的关键靶点.     

Sleep quality and risk of cancer: findings from the English longitudinal study of aging

Study ObjectiveTo prospectively examine the association between sleep quality and incident cancer risk in the elderly.MethodsA total of 10,036 participants aged ≥50 years free of cancer at baseline from the English Longitudinal Study of Ageing at wave 4 (2008) were included, and followed up until 2016. The primary endpoint was new onset physician-diagnosed cancer. Sleep quality was assessed by four questions regarding the frequency of sleep problems and overall subjective feeling of sleep quality in the last month, with higher score denoting poorer sleep quality. The multivariable Cox regression model was used to calculate hazard ratio (HR) with 95% confidence interval (CI) for incident cancer risk according to sleep quality.ResultsAt 8-year follow-up, a total of 745 (7.4%) participants developed cancer. Compared with good sleep quality at baseline, HR (95% CI) for incident cancer risk was 1.328 (1.061, 1.662) for intermediate quality, 1.586 (1.149, 2.189) for poor quality. Similarly, compared with maintaining good sleep quality in the first 4 years, HR (95% CI) for incident cancer risk was 1.615 (1.208, 2.160) for maintaining intermediate quality and 1.608 (1.043, 2.480) for maintaining poor quality. The exclusion of participants with family history of cancer or abnormal sleep duration yielded consistent results.ConclusionsPoor sleep quality is positively associated with the long-term risk of developing cancer in an elderly cohort. Both medical staffs and the general public should pay more attention to improving sleep hygiene.     

The boomerang effect of tuberculosis knowledge and self-efficacy on Chinese parents’ intention to seek timely treatment and adhere to doctors’ regimens

ObjectiveThe present study tested the level of tuberculosis (TB) knowledge of Chinese parents whose children attended kindergarten, primary school, and middle school, and examined whether their TB knowledge and self-efficacy in TB management exhibited a curvilinear relationship with their intention to seek timely TB treatment and adhere to doctors’ regimens if their children are infected with TB.MethodsAn online cross-sectional survey (N = 1129) was conducted. TB knowledge was assessed based on the manual provided by the Chinese Center for Disease Control and Prevention (CDC). Hierarchical polynomial regression was conducted to test the proposed curvilinear relationships.ResultsChinese parents lacked knowledge about risks of TB and how to prevent TB. TB knowledge and self-efficacy in TB management motivated Chinese parents to seek timely TB treatment and adhere to doctors’ regimens, but too much knowledge and self-efficacy predicted both intentions negatively.ConclusionExcessive levels of self-efficacy in self-management and health knowledge could backfire.Practice implicationPractitioners should elevate Chinese parents’ perceptions of severity of TB and susceptibility to TB. Additionally, health education should not be limited to providing medical facts but offer guidance on how to access professional medical resources. Self-efficacy in self-management should not be elevated.     

The role of innate immunity in myasthenia gravis

Myasthenia gravis (MG) is a T cell-driven, B cell-mediated and autoantibody-dependent autoimmune disorder against neuromuscular junctions (NMJ). Accumulated evidence has emerged regarding the role of innate immunity in the pathogenesis of MG. In this review, we proposed two hypothesis underlying the pathological mechanism. In the context of gene predisposition, on the one hand, Toll-like receptors (TLRs) pathways were initiated by viral infection in the thymus with MG to generate chemokines and pro-inflammatory cytokines such as Type I interferon (IFN), which facilitate the thymus to function as a tertiary lymphoid organ (TLO). On the another hand, the antibodies against acetylcholine receptors (AChR) generated by thymus then activated the classical pathways on thymus and neuromuscular junction (NMJ). Futher, we also highlight the role of innate immune cells in the pathogenic response. Finally, we provide some future perspectives in developing new therapeutic approaches particularly targeting the innate immunity for MG.     

Clinical implications of procalcitonin in Kawasaki disease: a useful candidate for differentiating from sepsis and evaluating IVIG responsiveness

Clinical and Experimental Medicine - Kawasaki disease (KD) is an acute systemic vasculitis and suspected to be triggered by several potential infections in which procalcitonin (PCT) experiences an...     

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma

Objective:Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma.Methods:A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection.Results:Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS.Conclusion:Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC.Advances in knowledge:We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.