Study of Serum Metabonomics and Formula-Pattern Correspondence in Coronary Heart Disease Patients Diagnosed as Phlegm or Blood Stasis Pattern Based on Ultra Performance Liquid Chromatography Mass Spectrometry

Objectives： To study the characteristics of serum metabonomics in coronary heart disease （CHD） patients diagnosed as phlegm or blood stasis pattern and explore effects of formula-pattern correspondence treatment. Methods： A total of 102 stable CHD patients were enrolled and divided into phlegm group （P group, n=52） and blood stasis group （BS group, n=50） according to pattern identification. Gualou Xiebai Banxia Decoction （瓜萎薤白半夏汤, GXBD） and Xuefu Zhuyu Decoction （血府逐瘀汤, XZD） were used as drug interventions. Relevant indicators of metabonomics were observed by ultra performance liquid chromatography mass spectrometry （UPLC-MS） and pattern recognition. Results： Levels of amino acids and phosphatidylethanolamine （PE） in the CHD group were much higher than those in healthy control group, while the levels of unsaturated fatty acids, sphingosine, Lyso, phosphatidylcholine （PC） were significantly lower （P〈0.01）. Most of the differential metabolites between the CHD and the healthy groups were also common metabolites of phlegm and blood stasis. 7（Z）, 10（Z）- hexadecadienoic acid and DPA were decreased in the P group and increased in the BS group. According to the quantity of retraced metabolites, improvement in metabonomics by formula-pattern correspondence was superior to that without correspondence in the BS group. Based on the varieties of metabolites, GXBD could improve the levels of docosapentaenoic acid （DPA）, sphingomyelin （SM） （d34：1）, and L-Lactic acid and XZD could ameliorate the levels of sphingosine and Vit E in the P group, in the BS group, GXBD could improve vitamin E level and XZD could make improvements in the levels of octadecanoic acid, phosphoglycerol, and SM （d34：1）. Conclusions： Phlegm and blood stasis in CHD patients present specific differential metabolites, and share common metabolites. Remarkable differences have been displayed in pathological properties and severity of phlegm and blood stasis. Patients with phlegm are more likely to have lipid metabolism disorders. However, in patients with blood stasis, problems mainly lie in glucose, protein and fat metabolism and the injury of vascular cell membrane is relatively severe. The metabolic disorder is more complicated in blood stasis pattem than that in phlegm pattem. Compared with non-correspondence, improvement of differential metabolites is more comprehensive and targeted in formulapattern correspondence with a better effect.

Inter-observer Reliability of Indicators and Decision of Pattern Identification Using Diagnostic Flowchart with Traditional Korean Medicine

Objective： To evaluate the consistency of patterns and pattern identification（PI）, and the improvement in the diagnosis of blood stasis after the standard operating procedures（SOPs） were enhanced by using a diagnostic flowchart. Methods： A total of 358 subjects who were admitted by the Jaseng Hospital of Korean Medicine between June 2013 and December 2014 were included in the study. Each patient was independently diagnosed by two experts from the same department. In 2014, the SOPs included the use of a diagnostic flowchart for each indicator. Inter-observer consistency was assessed by simple percent agreement and by the kappa and AC1 statistics. Results： The improvements in inter-observer agreement for the indicators（for al patients） and PI were greater in 2014 than in 2013. In 2013, the j-value measure of agreement between the two experts ranged from ＂poor＂（κ=–0.051） to ＂good＂（κ=0.968）. The AC1 measure of agreement between the experts was generally high for the indicators and ranged from –0.010 to 0.978. In most cases, agreement was considerably lower when it was assessed by the j-values compared with the AC1 values. In 2014, the j-value measure of agreement on the indicators（for the subjects） general y ranged from poor to good, with the values ranging from –0.007 to 0.994. Moreover, the AC1 measure of agreement between the experts was general y high for al of the indicators and ranged from ＂moderate＂（AC1=0.408） to ＂excel ent＂（AC1=0.996）. Conclusions： In four examinations, there was moderate agreement between the clinicians on the PI indicators of blood stasis. To improve clinician consistency（e.g., in the diagnostic criteria used）, it is necessary to analyse the reasons for inconsistency and to improve clinician training.（Trial registration No. KCT0000916）