Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

Heat stroke alters hippocampal and cerebellar transmitter metabonomics

BACKGROUND:The mechanisms underlying heat stroke(HS)-induced hippocampal injury remain unclear.This study aimed to evaluate the HS-induced metabonomics of hippocampal and cerebellar transmitters.METHODS:The HS model was established with male Sprague-Dawley rats subjected to heat exposure of up to 42℃ at a humidity of(55.0±5.0)%.The hippocampal and cerebellar transmitters and metabolites of rats were tested via ultra-high-performance liquid chromatography–mass spectrometry(UPLC-MS/MS).The primary transmitters and metabolites were identified by principal component analysis(PCA)and orthogonal partial least square-discriminant analysis(OPLS-DA).The major metabolic pathways for HS were selected after enrichment.The brain injury was evaluated by histological tests.RESULTS:HS induced hippocampal and cerebellar injuries in rats.HS upregulated the protein levels of hippocampal glutamate,glutamine,gamma-aminobutyric acid,L-tryptophan(Trp),5-hydroxy-indoleacetic acid,and kynurenine;however,it downregulated asparagine,tryptamine,5-hydroxytryptophan,melatonin,3,4-dihydroxyphenylalanine(L-DOPA),and vanillylmandelic acid.HS also sharply elevated the protein levels of cerebellar methionine and Trp,and decreased the levels of serotonin,L-alanine,L-asparagine,L-aspartate,cysteine,norepinephrine,spermine,spermidine,and tyrosine.Hippocampal glutamate,monoamine transmitters,cerebellar aspartate acid,and catecholamine transmitters’metabolic pathways were identified as the main metablic pathways in HS.CONCLUSION:The hippocampus and cerebellum were injured in rats with HS,possibly induced the disorder of hippocampal glutamate and serotonin metabolism,cerebellar aspartate acid and catecholamine transmitter metabolism,and related metabolic pathways.

Metabonomic analysis of plasma biochemical changes in pyrexia rats after treatment with Gegenqinlian decoction,aspirin and itraconazole by UHPLC-FT-ICR-MS

A metabonomic approach involving an ultrahigh-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry(UHPLC-FT-ICR-MS)was used to investigate the changes in the endogenous metabolites in the plasma of rats with yeast-induced pyrexia treated with Gegenqinlian decoction(GQLD),aspirin and itraconazole.The differences in the small molecule profiles of treatment using traditional Chinese medicine,etiological treatment and symptomatic treatment were elucidated.Thirty-six plasma metabolites were identified or putatively identified,and the effects of the three medicines on the thirty-six metabolites were studied.Their metabolic pathways indicated that GQLD,aspirin and itraconazole ameliorated the rats with yeast-induced pyrexia predominantly by regulating the metabolisms of phospholipid,sphingolipid,fatty acid oxidation,fatty acid amides,amino acid and glycerolipid in vivo.The pharmacodynamics and metabonomic results showed that the three medicines exhibited the therapeutic effects on pyrexia by regulating the perturbations of multiple metabolisms.The study provided a scientific basis for an in-depth understanding of the therapeutic effects of GQLD,aspirin and itraconazole on rats with yeast-induced pyrexia.

A new metabonomics method for simultaneous determination of EFAs and NEFAs in plasma using GC-MS and its application

A new metabonomics method was developed for simultaneous qualitative and quantitative analysis on esterified and nonesterified fatty acids （EFAs and NEFAs） in plasma. Merely 10 μL of plasma was required. The pretreatment of the sample was simple without disposing the protein. After simple extraction and derivation, 15 FAs in plasma were precisely quantified. Gas chromatography tandem mass spectrometry （GC-MS） was used in the study and the quantities of the analytes, which varied in abundance over three orders of magnitude. The established method showed good accuracy. The curve correlation coefficients were all above 0.997. The RSDs of precision for all compounds were below 15% and recoveries were all between 80 and 110%. PLS-DA modal was used in the data management. 2009 Guo An Luo. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Investigation on Acute Biochemical Effects of Ce（NO3 ）3 on Liver and Kidney Tissues by MAS 1H NMR Spectroscopic-Based Metabonomic Approach

High resolution magic angle spinning （MAS）-^1H nuclear magnetic resonance （NMR） spectroscopic-based metabonomic approach was applied to the investigation on the acute biochemical effects of Ce（NO3）3. Male Wistar rats were administrated with various doses of Ce（NO3）3（2, 10, and 50 mg·kg^- 1 body weight）, and MAS ^1H NMR spectra of intact liver and kidney tissues were analyzed using principal component analysis to extract toxicity information. The biochemical effects of Ce（NO3）3 were characterized by the increase of triglycerides and lactate and the decrease of glycogen in rat liver tissue, together with an elevation of the triglyceride level and a depletion of glycerophosphocholine and betaine in kidney tissues. The target lesions of Ce（NO3）3 on liver and kidney were found by MAS NMR-based metabonomic method. This study demonstrates that the combination of MAS ^1H NMR and pattern recognition analysis can be an effective method for studies of biochemical effects of rare earths.

UPLC-Q/TOF-MS based metabonomics revealed protective effect of Terminalia chebula extract on ischemic stroke rats

Terminalia chebula(TC),a kind of Combretaceae,is a widely used herb in India and East Asia to treat cerebrovascular diseases.However,the potential mechanism of the neuroprotective effects of TC at the metabonomics level is still not unclear.The present study focused on the effects of TC on metabonomics in stroke model.In our study,rats were divided randomly into Sham,Model,and TC groups.The TC group were intragastricly administered with TC for 7 d after middle cerebral artery occlusion(MCAO)operation.The sham and the model groups received vehicle for the same length of time.Subsequently,the neuroprotective effects of TC were examined by neurological defects evalua⁃tion,infarct volume assessment,and identification of biochemical indicators for antioxidant and anti-inflammatory activi⁃ties.Further,metabonomics technology was employed to evaluate the endogenous metabolites profiling systematically.Consist to results of biochemical and histopathological assays,pattern recognition analysis showed a clear separation of the Model and the Sham group,indicating a recovery impact of TC on the MCAO rats.Moreover,12 potential biomarkers were identified in MCAO Model group,involved in energy(lactic acid,succinic acid,and fumarate),amino acids(leucine,alanine,and phenylalanine)and glycerophospholipid[PC(16∶0/20∶4),PC(20:4/20:4),LysoPC(18:0)and LysoPC(16:0)]metabolism,and other types of metabolism(arachidonic acid and palmitoylcarnitine).Notably,we found that metabolite levels of TC group were partially reversed to normal.In conclusion,TC could ameliorate MCAO rats by intervening with energy metabolism(glycolysis and TCA cycle),amino acid metabolism,glycerophospholipid metabolism and other types of metabolism.

Metabonomic window into hepatitis B virus-related hepatic diseases

Metabonomics has recently been widely used todiscover the pathogenesis and find potential metabolic markers with high sensitivity and specificity. Furthermore, it develops new diagnosis and treatment methods, increases early phase diagnosis rates of certain diseases and provides a new basis for targeted therapy. This review mainly analyzes the research progress of the metabonomics of hepatitis B virus(HBV)-related hepatic diseases, hoping to discover some potential metabolic markers for identification of HBVrelated hepatic diseases from other etiologies and for HBV-related hepatitis, liver cirrhosis and hepatocellular carcinoma. This can contribute to early discovery, diagnosis and treatment, eventually increasing the survival rate of HBV-related hepatic diseases.

Serum Metabonomics of Articular Cartilage Destruction Induced by T-2 Toxin in Wistar Rats

The molecular pathogenesis of T-2 toxin-induced cartilage destruction has not been fully unraveled yet. The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction. Thirty healthy male Wistar rats were fed a diet containing T-2 toxin （300 ng/kg chow） for 3 months. Histopathological changes in femorotibial cartilage were characterized in terms of chondrocyte degeneration/necrosis and superficial cartilage defect, and the endogenous metabolite profile of serum was determined by UPLC/Q-TOF MS. Treated rats showed extensive areas of chondrocyte necrosis and superficial cartilage defect in the articular cartilage. In addition, 8 metabolites were found to change significantly in these rats compared to the control group, including lyso PE （18：0/0：0）, lyso PC（14：0）, lyso PC[18：4 （6Z,9Z,12Z,15Z）], lyso PC[（16：1（9Z）], lyso PC（16：0）, L-valine, hippuric acid, and asparaginyl-glycine. These 8 metabolites associated with cartilage injury are mainly involved in phospholipid and amino acid metabolic pathways.

Urine Metabonomic Analysis of Interventions Effect of Soy Isoflavones on Rats Exposed to Di-(2-ethylhexyl) Phthalate

Objective Di-(2-ethylhexyl) phthalate(DEHP) is a ubiquitous environmental contaminant.As an endocrine disruptor,it seriously threatens human health and ecological environmental safety.This study examines the impact of intervention with soybean isoflavones(SIF) on DEHP-induced toxicity using a metabonomics approach.Methods Rats were randomly divided into control(H),SIF-treated(A,86 mg/kg body weight),DEHP-treated(B,68 mg/kg),and SIF plus DEHP-treated(D) groups.Rats were given SIF and DEHP daily through diet and gavage,respectively.After 30 d of treatment,rat urine was tested using UPLC/MS with multivariate analysis.Metabolic changes were also evaluated using biochemical assays.Results Metabolomics analyses revealed that p-cresol glucuronide,methyl hippuric acid,N1-methyl-2-pyridone-5-carboxamide,lysophosphatidycholine [18:2(9 Z,12 Z)] {lyso PC [18:2(9 Z,12 Z)]},lyso PC(16:0),xanthosine,undecanedioic acid,and N6-acetyl-l-lysine were present at significantly different levels in control and treatment groups.Conclusion SIF supplementation partially protects rats from DEHP-induced metabolic abnormalities by regulating fatty acid metabolism,antioxidant defense system,amino acid metabolism,and is also involved in the protection of mitochondria.

Effect of Rhei Radix et Rhizoma and Eupolyphaga Steleophaga on liver protection mechanism based on pharmacokinetics and metabonomics

Objective:Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)and hydrogen nuclear magnetic resonance spectroscopy(^(1)H NMR),the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma(RhRR,Dahuang in Chinese),Eupolyphaga Steleophaga(EuS,Tubiechong in Chinese)combined with RhRR acting on acute liver injury were explored.Methods:Models of acute liver injury were established,and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS.The liver tissues of different groups of mice were analyzed by ^(1)H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.Results:Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups,and the absorption of free anthraquinone in RhRR increased after compatibility with EuS.In addition,the pathological state of acute liver injury in rats can selectively promote the absorption of emodin,chrysophanol,physcion and aloe emodin.Through 15 differential metabolites in the liver tissue of acute liver injury mice,it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid,alanine,aspartic acid and glutamic acid,and phosphoinositide.However,the regulation of RhRR was weaker than that of RhRR-EuS.Conclusion:For the first time,we studied the pharmacokinetics and metabolomics differences of RhRREuS and RhRR in rats and mice with acute liver injury,in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.

Metabolite acetyl-L-carnitine participates in Bifidobacterium animalis F1-7 to ameliorate atherosclerotic inflammation by downregulating theTLR4/NF-κB pathway

This study aimed to explore the effect of Bifidobacterium animalis F1-7 on the improvement of atherosclerotic inflammation.Arteriosclerosis model ApoE^(-/-)mice were orally administered with B.animalis F1-7 for 12 weeks.The probiotic intervention reduced the plaque areas in aorta and the accumulation of macrophages,and downregulated the expression of toll-like receptor 4(TLR4)/nuclear factorκB(NF-κB)pathway to reduce the levels of inflammatory factors.The widely-targeted metabolomics analysis showed that acetyl-L-carnitine(ALC)in the intestine of atherosclerotic mice was significantly increased after B.animalis F1-7 intervention.Correlation analysis proved that ALC was associated with atherosclerotic inflammatory response.By using oxidized low density lipoprotein induced macrophage foam cells,we further verified that ALC could reduce lipid accumulation and inflammatory response in foam cells by downregulating the TLR4/NF-κB pathway.Finally,our results revealed that B.animalis F1-7 upregulated the metabolite ALC to downregulate the inflammatory responses,leading to the reduction of plaque accumulation of atherosclerosis.

Microbial phenolic metabolites 3-(3',4'-dihydroxyphenyl)propanoic acid and 3',4'-dihydroxyphenylacetic acid prevent obesity in mice fed high-fat diet

Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity.However,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic acid(DHPA)and 3’,4’-dihydroxyphenylacetic acid(DHAA),two main metabolites of dietary polyphenols,on obesity remains poorly understood.In this study,DHPA and DHAA were found to alleviate obesity,as well as regulate insulin resistance,lipid metabolism,and oxidative stress response in high-fat diet(HFD)mice.Surprisingly,the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome,but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion,tyrosine metabolism,pentose phosphate and tricarboxylic acid(TCA)cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Correlation analysis revealed that the differential metabolites are strongly associated with body weight,blood glucose,insulin level,and superoxide dismutase(SOD)enzyme activity.Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose,lipid and tyrosine metabolism pathways.

Metabonomic phenotype and identification of “heart blood stasis obstruction pattern” and “qi and yin deficiency pattern” of myocardial ischemia rat models

The traditional Chinese medicine concepts of "Xinxueyuzuzheng (heart blood stasis obstruction pattern)" and "Qiyinliangxuzheng (qi and yin deficiency pattern)" for myocardial ischemia rat models were constructed in the present study. Endogenous metabolites in rat plasma were analyzed using the GC/TOF-MS-based metabonomic method. Significant metabolic differences were observed between the control and two model groups, and the three groups were distinguished clearly by pattern recognition. Compared with those of the control, the levels of hydroxyproline, threonic acid, glutamine and citric acid were strikingly up or down-regulated in model rats. The metabolites contributing most to the classification between the two "pattern" rats were identified, such as valine, serine, threonine, ornithine, hydroxyproline, lysine, 2-hydroxybutanoic acid, 3-hydroxybutanoic acid, galactofuranose and inositol. These compounds were indicated as the potential biomarkers. The results suggested that the two "patterns" are involved in dysfunction in oxidative stress, energy metabolism and amino acid metabolism. These findings also provided the substantial foundation for exploring the scientific connotation of these two "Zhengxing (pattern types)" of myocardial ischemia, and "Bianzheng (pattern identification)".

A serum metabonomic study on the difference between alcoholand HBV-induced liver cirrhosis by ultraperformance liquid chromatography coupled to mass spectrometry plus quadrupole time-of-flight mass spectrometry

Background Liver cirrhosis is the fatal consequence of chronic hepatitis, making early diagnosis of liver cirrhosis critical. Liver biopsy is still the standard diagnostic method for liver cirrhosis, although its use in a broad population with alcoholism or hepatitis B virus （HBV） infection remains difficult. In this study, we used a metabonomic approach to detect potential biomarkers for early diagnosis of liver cirrhosis.Methods Serum specimens were collected prospectively from normal control subjects （n=22） and patients with alcoholic cirrhosis （n=18） or HBV-induced cirrhosis （n=19）. The serum metabonome was analyzed using ultraperformance liquid chromatography （LC）Rime-of-flight mass spectrometry （MS） integrated with chemometrics. The acquired LC-MS data were normalized and processed using principal component analysis （PCA） and partial least squares discrimination analysis （PLS-DA）.Results Significant differences in the metabonomics among the three groups were observed. Lysophosphatidyl cholines （LPCs） （LPC C16：0, LPC C18：0, LPC C18：2, LPC C18：3, LPC C20：3, LPC C20：5） were decreased in the serum of patients with hepatic cirrhosis, whereas bile acids （glycocholic acid, glycochenodeoxycholic acid）, hypoxanthine, and stearamide were increased in the serum of patients with hepatic cirrhosis. These metabolites are considered ＂common＂biomarkers for hepatic cirrhosis. Oleamide and myristamide were increased in the serum of patients with alcoholic cirrhosis but decreased in those with HBV-induced cirrhosis. These could be specific biomarkers for differential diagnosis between alcohol- and HBV-induced hepatic cirrhosis.Conclusions There are significant metabonomic differences between alcohol- and HBV-induced liver cirrhosis.Metabonomics is a top-down systems biology tool for conducting research on clinical problems.

Establishing 1H nuclear magnetic resonance based metabonomics fingerprinting profile for spinal cord injury： a pilot study

Background Spinal cord injury （SCI） is a complex trauma that consists of multiple pathological mechanisms involving cytotoxic, oxidation stress and immune-endocrine. This study aimed to establish plasma metabonomics fingerprinting atlas for SCI using 1H nuclear magnetic resonance （NMR） based metabonomics methodology and principal component analysis techniques.Methods Nine Sprague-Dawley （SD） male rats were randomly divided into SCI, normal and sham-operation control groups. Plasma samples were collected for 1H NMR spectroscopy 3 days after operation. The NMR data were analyzed using principal component analysis technique with Matlab software.Results Metabonomics analysis was able to distinguish the three groups （SCI, normal control, sham-operation）. The fingerprinting atlas indicated that, compared with those without SCI, the SCI group demonstrated the following characteristics with regard to second principal component： it is made up of fatty acids, myc-inositol, arginine, very low-density lipoprotein （VLDL）, low-density lipoprotein （LDL）, triglyceride （TG）, glucose, and 3-methyl-histamine.Conclusions The data indicated that SCI results in several significant changes in plasma metabolism early on and that a metabonomics approach based on 1H NMR spectroscopy can provide a metabolic profile comprising several metabolite classes and allow for relative quantification of such changes. The results also provided support for further development and application of metabonomics technologies for studying SCI and for the utilization of multivariate models for classifying the extent of trauma within an individual.

Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry

Shuang-huang-lian Injection(SHLI) is the first successfully developed drug from traditional Chinese medicine(TCM) powder for injection,since its use for the treatment of acute respiratory tract infection,pneumonia,influenza,etc.At the same time,its allergic reactions have also emerged,which limits clinical applications.However,few scholars pay attention to the mechanism of allergic reactions.In this present study,metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction;we and analyzed the metabolites,metabolic pathway,and the mechanism which were closely related to the allergic reactions.The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed.Based on the UPLC-Q-TOF/MS metabonomics,we carried out the pattern recognition analysis,selected potential biomarkers associated with allergic reactions,and explored the pathological mechanism for SHLI induced allergic reaction,which laid the foundation for the safety research of SHLI.Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction;we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved,such as metabolism of linolenic acid,phenylalanine,amino acid,2-oxo acid,and purine and other metabolic pathways.

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.

Metabonomics:A Useful Tool to Reveal Underlying Relationships between Altered Chinese Medicine Syndromes and Ultrafiltration in Treatment of Heart Failure

Objective:To reveal the underlying relationships between Chinese medicine(CM)syndromes and ultrafiltration(UF)in the treatment of heart failure based on a metabonomic approach.Methods:Seventeen acute decompensated heart failure(ADHF)patients were enrolled,and their CM syndromes before and after UF were collected.In addition,their venous plasma collected before and after UF was used for liquid chromatographmass spectrometer-based metabonomic analysis.Both reversed phase liquid chromatography and hydrophilic interaction liquid chromatography were used to analyze the plasma samples.Partial least-squares to latent structure-discriminant analyses were used for data analysis.Results:An obvious difference was observed preand post-treatment.A total of 17 potential biomarkers associating with alterd syndromes with UF including hypoxanthine,1-methylhistidine,phytosphingosine,O-decanoyl-R-carnitine,etc.were screened out,showing a significant change after UF.The major adjusted m etabolic pathways were purine metabolism,histidine metabolism,leucine and isoleucine metabolism,arginine and proline metabolism,carnitine shuttle,sphingolipid metabolism and phospholipid metabolism.Conclusions:Metabonomic approach is a useful tool to identify potential biomarkers of altered syndromes link to UF and could provide a theoretical basis for further research on the therapeutic mechanism of UF combined with CM.

Study on Correspondence between Prescription and Syndrome and the Essence of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease Based on Metabonomics

Studying the essence of a syndrome has been a key challenge in the field of Chinese medicine.Until now,due to limitations of the methods available,the progress towards understanding such complicated systems has been slow.Metabonomics encompasses the dynamics,composition and analysis of metabolites,enabling the observation of changes in the metabolic network of the human body associated with disease.Being from the point of view of the whole organism,metabonomics provides an opportunity to study the essence of a syndrome to an unprecedented level.Phlegm and blood stasis syndrome is the main syndrome associated with coronary heart disease（CHD）,which bring difficulties in clinical treatment due to difficulties associated with differentiation of symptoms and signs.The fundamental differences of material between the two also need to be interpreted.The authors consider that we can use the method of combining a disease（in this case CHD）with associated syndromes（phlegm and blood stasis syndrome）to select patients with phlegm and blood stasis syndrome of CHD,and utilize metabonomics to explore the essence of the syndrome by difference analysis of metabolite spectra.Meanwhile,we can study the syndrome in CM,observe the change regularity of metabolism spectra after the treatment of corresponding and non-corresponding prescription and syndrome,in order to validate the material fundament in the progress of syndrome formation and their differences.This will not only have great significance in enhancing the ability to identify syndrome of phlegm and blood stasis in CHD and to establish the clinical curative criteria,but will also offer a new approach of studying the essence for a syndrome using metabonomics.