基于网络药理学和分子对接技术探讨生脉注射液抗新型冠状病毒肺炎的作用机制

目的采用网络药理学与分子对接技术探讨生脉注射液的活性成分和治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法利用TCMSP及BATMAN-TCM数据库筛选生脉注射液的活性化合物,通过TCMSP及Targetnet在线数据库预测作用靶点,通过Cytoscape3.7.1构建活性成分-作用靶点网络图;在GeneCards及OMIM数据库中以"coronavirus pneumonia"为关键词搜索冠状病毒肺炎相关疾病靶点,与生脉注射液化合物靶点进行交集筛选出共同靶点作为研究靶点,将共同靶点导入STRING数据库获取数据后在Cytoscape 3.7.1软件中构建蛋白质-蛋白质相互作用网络图;利用R语言进行GO(gene ontology)功能、KEGG(Kyoto encyclopedia of genes and genomes)通路富集分析,预测其作用机制,并构建"成分-靶点-通路"网络图;通过DiscoveryStudio 2.5软件对关键靶点进行分子对接分析。结果生脉注射液筛选得到22个活性化合物,分别为邻苯二甲酸二辛酯、β-谷甾醇、当归酰基戈米辛O、戈米辛A、戈米辛R、五味子丙素、内南五味子酯乙、长南酸、南五味子内酯、香蒲木脂素B、新杜松烷酸A、新杜松烷酸B、新杜松烷酸C、新南五味子木脂宁、五味子内酯A、五味子内酯E、五味子酸、尿苷、薯蓣皂苷元、鸟嘌呤核苷、N-反式阿魏酰酪胺、豆甾醇。相应作用靶点224个,与COVID-19的共同靶点16个,分别为CASP3、CASP8、PTGS2、BCL2、BAX、PRKCA、PTGS1、PIK3CG、F10、NOS3、DPP4、NOS2、TLR9、ACE、ICAM1、PRKCE,关键靶点涉及CASP3、PTGS2、NOS2、NOS3、ICAM1。GO功能富集分析得到生物过程(BP)条目771个,细胞组成(CC)条目11个,分子功能(MF)条目79个。KEGG通路富集分析筛选得到67条(P0.05)信号通路,主要涉及糖尿病并发症AGE-RAGE信号通路、凋亡通路、P53信号通路、小细胞肺癌通路等。分子对接结果显示与关键靶点对接较好的成分有五味子内酯E、豆甾醇、N-反式阿魏酰酪胺。结论生脉注射液中的活性化合物五味子内酯E、豆甾醇、N-反式阿魏酰酪胺等能作用于CASP3、PTGS2、NOS2、NOS3等靶点调节多条信号通路发挥抗炎、免疫调节、抗休克、增加血氧饱和度等作用,从而可能发挥对COVID-19的治疗作用。     

颈内静脉球血氧饱和度监测的临床应用

颈内静脉球血氧饱和度(jugular venous bulb oxygen saturation,SjvO2)监测可及早发现脑氧供需的变化,尽早治疗以减轻脑组织的缺血缺氧性损伤。在神经外科手术、体外循环(cardiopulmonary bypass,CPB)和特殊体位手术中应用广泛,与脑组织氧分压(partial oxygen pressure of brain tissue,PbtO2)和近红外光谱对比有其优势,还可用于围手术期生理探索、指导过度通气、综合脑保护和多模式监测等诊治手段。     

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.     

Switching from intravenous to oral antibiotics in hospitalized patients with community-acquired pneumonia: A real-world analysis 2010–2018

The Japanese Respiratory Society 2017 guidelines strongly recommend switching from intravenous (IV) to oral antibiotics in patients with community-acquired pneumonia (CAP), following improvement in clinical symptoms and laboratory findings. Here, we retrospectively investigated the real-world, nationwide treatment and switching patterns for hospitalized patients with CAP in Japan using administrative data from 372 Japanese Diagnosis Procedure Combination hospitals from April 2010 to December 2018. Hospitalizations for CAP (patient age ≥20 years) with an A-DROP classification for CAP severity and IV antibiotics initiated on the admission date were included. Overall, 210,314 hospitalizations (moderate CAP: 61.7%) in 183,607 patients were analyzed. The median (interquartile range [IQR]) age at admission was 79 (70–86) years. Penicillin (51.9%) and cephalosporin (38.9%) were the most common IV antibiotic classes used and the median (IQR) duration of IV use was 8 (6–11) days. Switching to oral antibiotics during a hospitalization occurred in 30.1% (n = 63,311) of patients after a median (IQR) of 7 (5–10) days of IV treatment. The most frequently used oral antibiotic classes after a switch were fluoroquinolone (45.9%) and penicillin (24.8%). The switch rate was higher among hospitalizations with milder CAP, in respiratory medicine ward and in larger hospitals. The overall switch rates did not change over the study period. The findings from this analysis suggest that early switch from IV to oral antibiotics was not widely implemented during the 8 years of the study period. Further observation will be needed to see the potential impact of the guidelines update in 2017 in Japan.     

氯胺酮麻醉前不同时间肌内注射阿托品对小儿呼吸道的影响

目的探讨氯胺酮麻醉前不同时间肌内注射阿托品对小儿呼吸道的影响。方法将2012年1月至2013年6月在廊坊市第四人民医院住院的100例患儿按随机数字表法分为两组:A组(50例)于氯胺酮麻醉前30~60 min肌内注射阿托品(0.02 mg/kg),B组(50例)阿托品(0.02 mg/kg)与氯胺酮同时间肌内注射。两组患儿均于氯胺酮肌内注射2~4 min后入室准备手术,术中观察记录两组患儿呼吸道和肺部的听诊变化及脉搏血氧饱和度(Sp O2)变化。结果 A组Ⅰ级(即呼吸道未受影响)44例,Ⅱ级以上(即呼吸道受到不同程度影响)6例,阳性率为12%(6/50);B组Ⅰ级33例,Ⅱ级以上17例,阳性率为34%(17∕50)。两组患儿呼吸道受影响程度的比较,差异有统计学意义(P<0.01)。结论小儿氯胺酮麻醉前30 min肌内注射阿托品,能有效降低氯胺酮对患儿呼吸道的影响,提高术中患儿的安全系数。     

血氧测量快速滤波与实时算法设计

目的血氧饱和度是人体的重要参数,为适应无线监护系统的需要,针对无线血氧测量节点内存小、运算速度慢的特点,本文设计了一套递推型快速处理算法。方法该算法充分利用递推方式和形态滤波算法过程的中间结果,加速滤波算法的处理速度,提取出测量和控制的关键数据,保证了数据的快速处理和测量系统的实时控制。结果通过分析采样数据和模拟处理过程发现,该算法可有效消除基线漂移、抖动等干扰,保证测量的稳定可靠。结论该算法计算量小,抗干扰能力强,适合无线血氧测量节点实时测量的需求。