OBJECTIVETo investigate the underlying metabolomic profifiling of coronary heart disease (CHD) with blood stasis syndrome (BSS).

METHODSCHD model was induced by a nameroid constrictor in Chinese miniature swine. Fifteen miniature swine were randomly divided into a model group (n=9) and a control group (n=6), respectively according to arandom number table. After 4 weeks, plasma hemorheology was detected by automatic hemorheological analyzer, indices including hematocrit, plasma viscosity, blood viscosity, rigidity index and erythrocyte sedimentation rate; cardiac function was assessed by echocardiograph to detect left ventricular end-systolic diameter (LVED), left ventricular end-diastolic diameter (LVEDd), ejection fraction (EF), fractional shortening (FS) and other indicators. Gas chromatography coupled with mass spectrometry (GC-MS) and bioinformatics were applied to analyze spectra of CHD plasma with BSS.

RESULTSThe results of hemorheology analysis showed signifificant changes in viscosity, with low shear whole blood viscosity being lower and plasma viscosity higher in the model group compared with the control group. Moreover, whole blood reduction viscosity at high shear rate and whole blood reduction viscosity at low shear rate increased signifificantly (P <0.05). The echocardiograph results demonstrated that cardiac EF and FS showed signifificant difference (P <0.05), with EF values being decreased to 50% or less. The GC-MS data showed that principal component analysis can clearly separate the animals with BSS from those in the control group. The enriched Kyoto Encyclopedia of Genes and Genomes biological pathways results suggested that the patterns involved were associated with dysfunction of energy metabolism including glucose and lipid disorders, especially in glycolysis/gluconeogenesis, galactose metabolism and adenosine-triphosphate-binding cassette transporters.

CONCLUSIONSGlucose metabolism and lipid metabolism disorders were the major contributors to the syndrome classifification of CHD with BSS.

Animals ; Coronary Angiography ; Coronary Disease ; blood ; diagnostic imaging ; metabolism ; surgery ; Disease Models, Animal ; Electrocardiography ; Gas Chromatography-Mass Spectrometry ; Hemorheology ; Metabolome ; Metabolomics ; methods ; Principal Component Analysis ; Sus scrofa ; Tricarboxylic Acids ; metabolism

OBJECTIVETo investigate the mechanisms of Panax notoginseng saponins (PNS) in treating coronary heart disease (CHD) by integrating gene interaction network and functional enrichment analysis.

METHODSText mining was used to get CHD and PNS associated genes. Gene-gene interaction networks of CHD and PNS were built by the GeneMANIA Cytoscape plugin. Advanced Network Merge Cytoscape plugin was used to analyze the two networks. Their functions were analyzed by gene functional enrichment analysis via DAVID Bioinformatics. Joint subnetwork of CHD network and PNS network was identifified by network analysis.

RESULTSThe 11 genes of the joint subnetwork were the direct targets of PNS in CHD network and enriched in cytokine-cytokine receptor interaction pathway. PNS could affect other 85 genes by the gene-gene interaction of joint subnetwork and these genes were enriched in other 7 pathways. The direct mechanisms of PNS in treating CHD by targeting cytokines to relieve the inflflammation and the indirect mechanisms of PNS in treating CHD by affecting other 7 pathways through the interaction of joint subnetwork of PNS and CHD network. The genes in the 7 pathways could be potential targets for the immunologic adjuvant, anticoagulant, hypolipidemic, anti-platelet and anti-hypertrophic activities of PNS.

CONCLUSIONSThe key mechanisms of PNS in treating CHD could be anticoagulant and hypolipidemic which are indicated by analyzing biological functions of hubs in the merged network.

Coronary Disease ; drug therapy ; genetics ; Gene Expression Profiling ; Gene Regulatory Networks ; drug effects ; Humans ; Panax notoginseng ; chemistry ; Phytotherapy ; Saponins ; pharmacology ; therapeutic use

OBJECTIVETo observe the effificacy and safety of Qiaoshao Formula (, QSF) on patients with lifelong premature ejaculation (LPE) of Gan (Liver) depression and Shen (Kidney) defificiency syndrome.

METHODSA total of 60 LPE patients were randomly divided into treatment (QSF) and control (dapoxetine) groups. The treatment group received QSF twice a day and the control group received dapoxetine 1 to 2 h prior to planned sexual intercourse for 4 weeks. The outcomes included intra-vaginal ejaculation latency time (IELT), premature ejaculation diagnostic tool (PEDT), clinical global impression of change (CGIC), scores of Chinese medicine symptoms (CMSS), sex life satisfaction (SLS) and adverse events (AEs).

RESULTSIn the treated group, the median IELT was 3 min vs. 1.5 min before and after treatment (P<0.05). PEDT in the treated group was reduced to 11.76±1.68 from 15.83±2.30 after treatment (P<0.05). Besides, patient's SLS was improved from 1.30±0.05 to 6.30±0.04 (P<0.05), and spouse's SLS was increased from 1.30±0.to 6.10±0.06 (P<0.05); CMSS was decrease from 14.86±3.02 to 9.62±2.87 (P<0.05). In addition, no significant AE was observed in both groups.

CONCLUSIONQSF may be effective and safe on LPE patients with Gan depression and Shen defificiency syndrome.

Adult ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Kidney ; pathology ; Liver ; pathology ; Male ; Middle Aged ; Personal Satisfaction ; Premature Ejaculation ; diagnosis ; drug therapy ; Syndrome ; Time Factors ; Treatment Outcome ; Young Adult

OBJECTIVETo 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 flflowchart. 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 flflowchart for each indicator. Inter-observer consistency was assessed by simple percent agreement and by the kappa and AC1 statistics.

RESULTSThe improvements in inter-observer agreement for the indicators (for all 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) generally 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 generally high for all of the indicators and ranged from "moderate" (AC1=0.408) to "excellent" (AC1=0.996).

CONCLUSIONSIn 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).

OBJECTIVETo investigate the protective effects of Chinese medicine formulation Chaihu Shugan San (, CHSGS) on nonalcoholic fatty liver disease (NAFLD) in rats with insulin resistance (IR) and its molecular mechanisms.

METHODSMale Sprague-Dawley rats were randomly divided into six groups: the control group, the model group, Dongbao Gantai group (, DBGT, 0.09 g methionine/kg), CHSGS high-dose group (CHSG-H, 12.6 g crude drug/kg), CHSGS medium-dose group (CHSG-M, 6.3 g crude drug/kg), and CHSGS low-dose group (CHSG-L, 3.15 g crude drug/kg). After establishing the NAFLD rat model and treatment for 8 weeks, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), fasting blood glucose (FBG), fasting insulin (FINS) contents in blood serum, and TC, TG contents in the hepatic homogenate were measured by an automatic biochemical analyzer, and a homeostasis model assessment was applied to assess the status of IR, insulin sensitivity index (ISI), and homeostasis model assessment for insulin secretion (HOMA-IS). The expression levels of adiponectin and leptin mRNA in liver tissue were analyzed by reverse transcription polymerase chain reaction. Pathological changes of livers were observed by hematoxylin-eosin staining of paraffin section.

RESULTSCompared with the model group, the serum levels of TC, TG, FFA, FBG, FINS, IRI, ISI, and the liver levels of TC and TG in CHSG-H, CHSG-M, CHSG-L groups showed significant declines (P<0.01 or P<0.05); the serum levels of HDL-C, HOMA-IS were significantly increased (P<0.01 or P<0.05); the expression of leptin mRNA was dramatically decreased and the expression of adiponectin mRNA was increased in the hepatic tissue (P<0.01 or P<0.05). The fatty deposition of liver cells could also be alleviated.

CONCLUSIONCHSGS could up-regulate the expression of adiponectin mRNA and down-regulate the expression of leptin mRNA on the liver, suggesting the CHSGS had positive therapeutic effect on NAFLD in rats with IR.

OBJECTIVESTo observe the regulation of Chinese herbal medicine, Modifified Qing'e Pill (, MQEP), on the expression of adiponectin, bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG) and other potentially relevant risk factors in patients with nontraumatic osteonecrosis of the femoral head (ONFH).

METHODSA total of 96 patients with nontraumatic ONFH were unequal randomly divided into treatment group (60 cases) and control group (36 cases). The treatment group were treated with MQEP while the control group were treated with simulated pills. Both groups were given caltrate D. Six months were taken as a treatment course. Patients were followed up every 2 months. The levels of plasma adiponectin, BMP2, OPG, von Willebrand factor (vWF), von Willebrand factor cleaving protease (vWF-cp), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), C-reactive protein (CRP), blood rheology, bone mineral density (BMD) of the femoral head and Harris Hip Score were measured before and after treatment.

RESULTSAfter 6 months of treatment, compared with the control group, patients in the treatment group had signifificantly higher adiponectin and BMP2 levels (P<0.01 and P=0.013, respectively), lower vWF, PAI-1 and CRP levels (P=0.019, P<0.01 and P<0.01, respectively), and lower blood rheology parameters. BMD of the femoral neck, triangle area and Harris Hip Score in the treatment group were signifificantly higher than those in the control group. Moreover, plasma adiponectin showed a positive association with BMP2 (r=0.231, P=0.003) and a negative association with PAI-1 (r=-0.159, P<0.05).

CONCLUSIONMQEP may play a protective role against nontraumatic ONFH by increasing the expression of adiponectin, regulating bone metabolism and improving the hypercoagulation state, which may provide an experimental base for its clinical effects.

Adiponectin ; metabolism ; Adult ; Blood Coagulation Factors ; metabolism ; Bone Density ; drug effects ; Bone Morphogenetic Protein 2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Femur Head Necrosis ; blood ; drug therapy ; physiopathology ; Humans ; Male

OBJECTIVETo evaluate the effect of Chinese medicine Haoqin Qingdan Decoction (, HQD) for febrile disease dampness-heat syndrome (FDDHS).

METHODSForty mice were divided into four groups, including normal control, FDDHS (induced by Radix et Rhizoma Rhei recipe and influenza virus A1 FM1 model), HQD, and the ribavirin groups (10 in each). The normal control and FDDHS groups were administered normal saline. HQD and the ribavirin groups were administered HQD and ribavirin intragastrically once daily at a dose of 64 g/(kg d) and 0.07 g/(kg d), respectively for 7 days. Lethargy, rough hair, diarrhea, tongue color and sole color were evaluated for pathological changes in morphology. The tongue and lung tissues were collected for histology. The CD14 and toll-like receptor 4 (TLR4) expression levels were measured using real-time quantitative polymerase chain reaction.

RESULTSMore than 80% of the FDDHS mice showed hypokinesia and lethargy, and pathological changes associated with rough hair, diarrhea, tongue color and sole color. With advanced treatment for 7 days, the thick greasy tongue fur of the HQD and ribavirin groups were thinner than that of the FDDHS group (P<0.05), and it was the thinnest in the ribavirin group as compared with that in other groups (P<0.05). The CD14 and TLR4 expression levels in the lung tissues of HQD and ribavirin groups significantly delined compared with the model group (P<0.05 or P<0.01). CD14 was down-regulated more remarkably in the HQD group compared with the ribavirin group (P<0.05), whereas the converse was true with TLR4 (P<0.05).

CONCLUSIONSWe established a FDDHS mouse model showing systemic clinical symptoms. Both HQD and ribavirin can inhibit the expression of CD14 and TLR4 in FDDHS mice, while the effect of ribavirin might be much more violent. The expression changes of CD14 and TLR4 consistently refers to lipopolysaccharide, the commonly and hotly inducing factor in FDDHS.

Animals ; Behavior, Animal ; Disease Models, Animal ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fever ; drug therapy ; pathology ; Gene Expression Profiling ; Lipopolysaccharide Receptors ; genetics ; metabolism ; Lung ; drug effects ; pathology ; Mice, Inbred BALB C ; Ribavirin ; pharmacology ; therapeutic use ; Syndrome ; Toll-Like Receptor 4 ; genetics ; metabolism

OBJECTIVETo explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction (, ZMAD) on the blood parameters and myocardium of high altitude polycythemia (HAPC) model rats.

METHODSForty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L. (RRL) and ZMAD groups (10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL (20 mL/kg) and ZMAD (7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy.

RESULTSCompared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHdG levels, and also increased the erythrocyte deformation index (P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group.

CONCLUSIONZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.

Traditional Chinese medicine (TCM) holds a holistic theory, and specializes in balancing disordered human body using numerous natural products, particularly Chinese herbal formulae. TCM has certain treatment advantages for patients suffering from various complex diseases. However, due to the complex nature of TCM, it remains difficult to unveil such holistic medicine by the current reductionism research strategies, which treat both herbal ingredients and targets in isolation. Recently, an emerging network pharmacology approach has been introduced to tackle this bottleneck problem. A TCM-derived novel therapeutic concept, "network target", which is different from the Western medicine's "onetarget" concept, has been proposed from China. The network target strategy is able to illustrate the complex interactions among the biological systems, drugs, and complex diseases from a network perspective, and thus provides an innovative approach to access ancient remedies in a precision manner and at a systematic level, which also highlights TCM's potential in current medical systems.
Herbal Medicine ; Humans ; Medicine, Chinese Traditional

Pathological angiogenesis of liver which includes liver sinusoidal capillarization due to lose of fenestraes of liver sinusoidal endothelial cells (LSECs) and formation of new vascular, is a crucial mechanism responsible for origination and development of liver fifibrosis and closely involves in the development of cirrhosis and hepatic cancer. Anti-neovascularization medicine such as sorafenib can decrease portosystemic shunts, improve splanchnic hyperdynamic circulation, lower portal hypertension, while it can not be applied in clinic due to its serious toxic and side reactions. Chinese herbal formula can effectively inhibit pathological angiogenesis of liver, improve microcirculation of liver, and decrease the probability of gastrointestinal hemorrhage in cirrhotic patients. Different Chinese herbal formula are of different characteristics on inhibiting pathological angiogenesis in liver fifibrosis, which partly explains synergistic effect of different compatibility of Chinese materia medica and opens up good vista for Chinese medicine against liver fifibrosis through inhibiting angiogenesis.
Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Esophageal and Gastric Varices ; complications ; drug therapy ; Hemorrhage ; complications ; drug therapy ; Humans ; Liver Cirrhosis ; complications ; drug therapy ; Microcirculation ; drug effects ; Neovascularization, Pathologic ; complications ; drug therapy