EGFR mutation types and abundance were associated with the overall survival of advanced lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors

BackgroundEpidermal growth factor receptor tyrosine kinases inhibitors (EGFR-TKIs) are currently recognized as the standard treatment for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations. Clinically found patients with different EGFR mutational status have different prognosis.MethodsA retrospective cohort study was performed to explore the relationship between EGFR mutations and abundance with patient survival by using patient data from the Affiliated Cancer Hospital of Zhengzhou University between January 2013 and November 2016. All patients involved in the present study had sensitive EGFR mutations [either exon 19 deletion (DEL) or exon 21 L858R] and treated by EGFR-TKIs. They were followed up every three months until lost or dead. Mutation abundance was calculated as the copies of EGFR mutation divided by copies of EGFR locus, and the cut-off values for 19DEL and L858R were 4.9% and 9.5%, respectively.ResultsTotal of 236 patients were included, comprising 116 (49.2%) patients with 19DEL mutation and 120 (50.8%) patients with L858R mutation. The median follow-up duration was 23.2 months (95% CI: 14.9–26.7 months). Overall survival (OS) was significantly longer in patients with 19DEL mutation (20.9 months, 95% CI: 17.7–24.1 months versus 17.0 months, 95% CI: 14.4–19.6 months in patients with L858R; P=0.008) and in patients with high mutation abundance (20.9 months, 95% CI: 18.3–23.5 months versus 13.0 months, 95% CI: 10.3–15.7 months in patients with low mutation abundance; P<0.001). Multivariate Cox regression including age, performance status and tumor stage revealed that longer OS was independently associated with 19DEL mutation (HR: 0.48, 95% CI: 0.39–0.67, P=0.033) and high mutation abundance (HR: 0.62, 95% CI: 0.50–0.79, P=0.027).ConclusionsEGFR mutation types and abundance was associated with the patients’ survival which might be used to predict the efficacy of targeted therapy by EGFR-TKIs.     

膈肌深呼吸训练辅助药物治疗支气管哮喘慢性持续期患儿的效果

目的探讨膈肌深呼吸训练辅助药物治疗支气管哮喘慢性持续期患儿的临床疗效。方法选取2018年6月—2020年1月咸宁市某医院收治的200例支气管哮喘慢性持续期患儿,采用随机数字表法分为观察组与对照组,每组100例。对照组患儿给予药物雾化吸入治疗,观察组患儿在对照组基础上给予膈肌深呼吸训练辅助治疗。比较2组患儿的临床疗效,治疗前后实验室指标、肺功能及家属满意度。结果观察组患儿治疗总有效率为95.00%,高于对照组的79.00%,差异有统计学意义(χ²=11.317,P<0.05)。2组患儿治疗后血清免疫球蛋白E(Ig E)、白介素-4(IL-4)及肿瘤坏死因子α(TNF-α)水平低于治疗前,且观察组低于对照组,差异均有统计学意义(P<0.05)。2组患儿治疗后FEV1、FVC及PEF水平高于治疗前,且观察组高于对照组,差异均有统计学意义(P<0.05)。观察组患儿家属满意度为94.00%,高于对照组的77.00%,差异有统计学意义(χ²=11.656,P<0.05)。结论膈肌深呼吸训练辅助药物治疗慢性持续期支气管哮喘患儿疗效...     

热环境对机体功能影响的机制及防护研究进展

热环境增加高温作业人员发生热损伤的风险,充分认识热环境对高温作业人员机体的影响和危害,对提高高温作业人员防暑意识、减少作业时的职业性热损伤具有重要意义.笔者主要从热环境的定义、热环境对人体主要功能系统影响的机制、热应激的影响因素及防护研究进展进行综述,为高温作业人员对热致疾病的认识及防护提供参考.     

基于深度学习的超声影像诊断对终末期慢性肾病的价值

目的 探讨基于深度学习的卷积神经网络模型DenseNet121对终末期肾病的诊断价值.方法 回顾性选择2019年1月1日至9月30日期间中日友好医院诊断为终末期肾病的489张肾超声影像和对照组450张健康肾超声影像.采用深度卷积神经网络模型DenseNet121进行网络的训练和验证,把是否为终末期肾病作为参考标准.然后...     

Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4

Background/AimsBinge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs).MethodsSerum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used.ResultsA marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated.ConclusionsFormation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.     

rTMS及CBT-I对慢性失眠障碍患者治疗效果的随机对照研究

背景 目前,药物疗法是失眠障碍的一线治疗手段,但仍然存在着一定的不良反应。与药物治疗相比,重复经颅磁刺激（rTMS）和失眠的认知行为治疗（CBT-I）的不良反应较少、患者耐受性较好。目的 探讨rTMS与CBT-I治疗慢性失眠障碍的效果,以期为慢性失眠障碍患者提供更优的治疗方案。方法 选取2020年9月21日—2021年12月16日在内蒙古自治区精神卫生中心门诊或社区医院就诊的、符合《国际睡眠障碍分类第三版》（ICSD-3）诊断标准的慢性失眠障碍患者（n=50）,同期在社区招募与患者组年龄和性别相匹配的健康人作为对照组（n=16）。采用随机数字表法将慢性失眠障碍患者分为rTMS组与CBT-I组各25例,分别接受为期6周的rTMS或CBT-I干预。于干预前和干预后,慢性失眠障碍患者接受多导睡眠监测（PSG）以及匹兹堡睡眠质量指数量表（PSQI）、失眠严重程度指数量表（ISI）、重复性成套神经心理状态测验（RBANS）评定。对患者组和对照组进行静息态磁共振成像（rs-fMRI）扫描,并进行静息态低频振幅（ALFF）分析。将患者组和对照组ALFF值差异有统计学意义的脑区作为感兴趣区域（ROI）,将其作为种子点与患者全脑进行功能连接分析。结果 rTMS组和CBT-I组的PSQI评分、ISI评分以及RBANS中的即刻记忆、言语功能、延时记忆维度评分的时间效应均有统计学意义（F=41.160、69.615、47.923、12.090、28.193,P均<0.05）;两组总睡眠时间的时间效应、睡眠效率的时间效应和组别效应以及N1%的时间效应均有统计学意义（F=8.995、12.414、4.342、7.806,P均<0.05）。干预后,CBT-I组睡眠效率高于干预前（t=-2.785,P<0.05）。rTMS组眶部额上回与左侧豆状壳核（t=4.991,P<0.05）、右内侧和旁扣带回（t=4.471,P<0.05）和右侧中央后回（t=4.922,P<0.05）之间的功能连接增强,CBT-I组眶部额上回与左侧额中回之间的功能连接增强（t=6.586,P<0.05）。结论 rTMS及CBT-I可能有助于改善慢性失眠障碍患者的失眠情况和认知功能。     

Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota

Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites.     

Association between Excessive Dietary Branched-Chain Amino Acids Intake and Hypertension Risk in Chinese Population

The dietary intake of branched-chain amino acids (BCAAs) has been reported to be associated with both elevated blood pressure (BP) and hypertension risk, while published findings were inconsistent, and the causality has never been well disclosed. We performed this prospective study aiming to find out the relationship between dietary BCAAs intake and hypertension risk in the Chinese population. A total of 8491 participants (40,285 person-years) were selected. The levels of dietary BCAAs intake were estimated using the 24-h Food Frequency Questionnaire. Associations of both BP values and hypertension risk with per standard deviation increase of BCAAs were estimated using linear and COX regression analysis, respectively. The hazard ratios and 95% confidence interval were given. Restricted cubic spline analysis (RCS) was used to estimate the nonlinearity. Both systolic and diastolic BP values at the end points of follow-up were positively associated with dietary BCAAs intake. Positive associations between BCAAs intake and hypertension risk were shown in both men and women. By performing a RCS analysis, the nonlinear relationship between BCAAs intake and hypertension was shown. As the intake levels of Ile, Leu, and Val, respectively, exceeded 2.49 g/day, 4.91 g/day, and 2.88 g/day in men (2.16 g/day, 3.84 g/day, and 2.56 g/day in women), the hypertension risk increased. Our findings could provide some concrete evidence in the primary prevention of hypertension based on dietary interventions.