Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region

IntroductionInherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer.MethodsWe conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer.ResultsWe detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722–0.820; p value 5.31 × 10^-16), rs380286 (OR: 0.770, 95% CI: 0.723–0.820; p value 4.32 × 10^-16), and rs4975616 (OR: 0.778, 95% CI: 0.730–0.829; p value 1.04 × 10^-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate.ConclusionsWe found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.     

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.     

宝石CT碘-水基图在急性脑梗死介入治疗后的应用

目的探讨宝石CT碘-水基图在急性脑梗死介入治疗后的诊断价值。方法 31例急性脑梗死患者介入治疗后即刻宝石CT平扫QC图发现颅内异常高密度影,采用碘-水基图进行重建分析,同时测定高密度影碘基值、水基值,并与术后24 h普通CT复查诊断结果作比较。结果通过采用碘-水基图,17例诊断为碘对比剂渗出,14例诊断为脑出血转化,与术后24 h普通CT复查诊断结果完全一致(Kappa=1,P0.01);术后即刻碘基图之碘基值:碘对比剂渗出(32.09±5.36) g/L,脑出血转化(6.86±2.26) g/L,二者差异有统计学意义(t=53.291,P0.01);术后即刻水基图之水基值:碘对比剂渗出(1 027.93±8.29) g/L,脑出血转化(1 069.68±7.18) g/L,二者差异有统计学意义(t=-8.897,P0.01)。结论宝石CT碘-水基图可以准确诊断急性脑梗死介入治疗后颅内碘对比剂渗出和脑出血转化,值得向临床介绍推广。     

艾烟的作用与安全性评价＊

艾灸作为中医学最古老的疗法之一，作用多样，应用广泛，疗效显著。随着科技的发展，人们对灸法的认识逐渐深入，其中艾烟的相关研究也硕果累累，其安全性广受关注。通过对艾烟作用和安全性评价研究中取得的成果进行归纳分析，以期为艾灸临床安全应用提供指导。     

The challenges in scoring hypopneas in children: is pulse wave amplitude drop the answer?

BackgroundIdentifying electroencephalogram (EEG) cortical arousals are crucial in scoring hypopneas and respiratory efforts related arousals (RERAs) during a polysomnogram. As children have high arousal threshold, many of the flow limited breaths or hypopneas may not be associated with visual EEG arousals, hence this may lead to potential underestimation of the degree of sleep disordered breathing. Pulse wave amplitude (PWA) is a signal obtained from finger photoplethysmography which correlates directly to finger blood flow. The drop in PWA has been shown to be a sensitive marker for subcortical/autonomic and cortical arousals. Our aim was to use the drop in PWA as a surrogate for arousals to guide scoring of respiratory events in pediatric patients.MethodsTen polysomnograms for patients between the ages of 5–15 years who had obstructive apnea-hypopnea indices between 1 and 5 events/hour were identified. Patients with syndromes were excluded. A drop in PWA signal of at least 30% that lasted for 3 s was needed to identify subcortical/autonomic arousals. Arousals were rescored based on this criteria and subsequently respiratory events were rescored. Paired t-tests were employed to compare PSG indices scored with or without PWA incorporation.ResultsThe sample of 10 children included 2 females, and the average age was 9.8 ± 3.1 years. Overall, polysomnography revealed an average total sleep time of 464.1 ± 25 min, sleep efficiency of 92% +/−4.2, sleep latency of 19.6 ± 17.0 min, rapid eye movement (REM) latency 143 ± 66 min, N1 3.9% +/−2.0, N2 50.3% +/−12.0, N3 28.2% +/−9.1, REM 16.7% +/−4.0, and wakefulness after sleep onset (WASO) 18.1 ± 7.5 min. Including arousals from PWA changes, respiratory indices significantly increased including total AHI (2.3 ± 0.7 vs 5.7 ± 2.1, p < 0.001), obstructive AHI (1.45 ± 0.7 vs 4.8 ± 1.8, p < 0.001), and RDI (2.36 ± 0.7 vs 7.6 ± 2.0, p < 0.001). Likewise, total arousal index was significantly higher (8.7 ± 2.3 vs 29.4 ± 6.5, p < 0.001).ConclusionsThe drop in pulse wave amplitude signal is a useful marker to guide scoring arousals that are not otherwise easily identified in pediatric polysomnography and subsequently helped in scoring respiratory events that otherwise would not be scored. Further studies are needed to delineate if such methodology would affect clinical outcome.     

细胞因子白细胞介素-4对认知功能改善的研究进展

白细胞介素4(IL-4)是T辅助2(Th2)介导的免疫反应的基本免疫调节细胞因子,IL-4具有复杂的信号系统和多效的功能,但在脑组织中,诸多研究发现IL-4可在炎症中保护认知功能。该文总结了关于IL-4保护认知功能的证据及机制,以及在阿尔茨海默病、缺血性脑血管病以及手术后认知功能障碍中IL-4保护认知功能的途径及证据。