Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A₂/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.     

隐身南新仓的低调奢华

置身RAIN CLUB的超凡境地中，美食、美酒和美妙的音乐是智灵的洗净，像干燥的北京城迎来第一场春天的“润”——稍显奢华。[编者按]     

眼针治疗阵发性室上性心动过速120例的即时疗效观察

目的:观察眼针对阵发性室上性心动过速的即时疗效。方法:选择符合诊断标准的门诊患者120例,针其眼针穴区:心区和上焦区。针后30分钟描记心电图,计算心率,观察眼针对阵发性室上性心动过速的影响。结果:显效103例,占85.83%;有效9例,占7.5%;无效8例,占6.66%;总有效率93.33%.结论:眼针对阵发性室上性心动过速有较好的即时疗效。     

Inhibition and reversal of platelet-rich arterial thrombus in vivo: direct vs. indirect factor Xa inhibition

BACKGROUND/OBJECTIVE: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. METHODS: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion, n=6); ZK-807834-Dose 2 (20 microg kg(-1) bolus + 0.75 microg kg(-1) min(-1) infusion; n=6); enoxaparin (1 mg kg(-1) bolus; n=6); or saline (n=6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. RESULTS: The prothrombin time ratio was 2.2 +/- 0.1; 1.4 +/- 0.3; 1.2 +/- 0.9 and 1.1 +/- 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 +/- 226 x 10(6) cm(-2); P = 0.008), whereas ZK-807834-Dose 2 (2325 +/- 768) and enoxaparin (1236 +/- 383) were not different from saline (2776 +/- 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 +/- 185). Neither ZK-807834-Dose 2 (1588 +/- 480) nor enoxaparin (1618 +/- 686) was different from saline control (2222 +/- 598). CONCLUSIONS: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective.     

Developmental Toxicity of Dimethylacetamide by Inhalation in the Rat

Developmental Toxicity of Dimethylacetamide by Inhalation inthe Rat. SOLOMON, H. M., FERENZ, R. L., KENNEDY, G. L., ANDSTAPLES, R. E. (1991). Fundam. Appl. Toxicol. 16, 414–422.Dimethylacetamide (DMAC) is a widely used industrial solvent.It has been reported to be teratogenic when given to rats byinjection or following dermal application. Most of these studiesemployed large single doses and did not examine both the fetaland the maternal response. In this study, groups of pregnantCrl:CD rats were exposed to 32, 100, or 282 ppm DMAC by inhalationfor 6 hr/day from Days 6 through 15 of gestation (day on whichcopulation plug was detected was termed Day 1G). A control groupof chambered pregnant rats was exposed simultaneously to aironly. All female rats were euthanized on Day 21G. At 282 ppm,both maternal weight gain during the exposure period and fetalweight were significantly decreased and accompanied by a significantdose-response trend. These effects were not seen in rats inhalingeither 32 or 100 ppm. Fetal resorptions were not increased inany of the groups exposed to DMAC. Fetal incidences of external,visceral, or skeletal variations and malformations were similarbetween the test and control groups. Therefore, both fetal andmaternal toxicity were noted at 282 ppm and the no-observedadverse-effect level under these experimental conditions was100 ppm for both the dam and the conceptus. DMAC was not demonstratedto produce malformations in the rat fetus even at a level thatwas toxic to the dam.     

武汉西马街社区成人健康相关危险因素调查

目的 探讨当地成人健康相关危险因素构成，尝试低费用下开展此类监测的方法。方法 依托教育系统对武汉市江岸区西马街地区成人进行随机抽样入户问卷调查。结果 人群吸烟率32．4％，男性吸烟率60．6％，中年人高于老年人，女性吸烟率5．9％；92．5％的人不愿意自己的孩子在将来成为烟民；人群饮洒率为26．5％，其中男性饮洒率51％，23．5％的饮酒者存在违意饮酒情节；33．3％的成人有体育锻炼习惯，其比例随文化程度的升高而升高；19％的人每周户外活动时间达不到1天1小时；35．6％的人存在体重过重问题，分解19．2％为超重，14．7％为肥胖，1．7％为Ⅱ度肥胖。人群自述（非现场测量）高血压患病率为11．1％，自述糖尿病患病率为2．8％，但自觉有糖尿病典型症状而从未检测血糖的比例达16％。结论 落实社区人群基础医学检查任务迫切，依托教育系统进行的成人健康相关危险因素监测方法足当前经济适用的监测方法。