Objectives This research explored the characteristics of changes in the serum metabolic profile of preeclampsia pregnancy(PE) to establish the disease distinguish model and screen characteristic metabolic markers with potential diagnostic value for preeclampsia.Methods From August 2014 to January 2016,samples in three groups were collected at Tianjin Third Central Hospital.Thirty-one clinically diagnosis patients with preeclampsia,25 normal pregnancy women and 29 healthy volunteers of childbearing age were enrolled.Ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze serum metabolites of PE group (31 patients with preeclampsia),P group (25 normal pregnancy women) and Normal group (29 healthy volunteers of childbearing age).Nonparametric test analyzes were used to analyze the data and find the specific metabolites.Results This research established the principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) disease distinguish model for PE group,P group and Normal group.To distinguish PE group,P group and Normal group,15 characteristic metabolites were identified.Eight kinds of glycerol phospholipid (including 7 kinds of hemolysis phosphatidyl choline and 1 kind of lysophospholipids acid) and 1 kind of sphingomyelin in PE group were higher than that of normal pregnancy group.The difference had statistically significant(Z of the metabolites were 2.32,3.34,3.21,2.60,2.22,3.40,3.58,5.84,2.70 respectively,all P<0.05).1,25-Dihydroxyvitamin D3-26,23-lactone and 24-Oxo-1alpha,23,25-trihydroxyvitamin D3 in PE group were higher than that of P group and Normal group,which had a statistics difference (Z of the metabolites were 2.01,3.89,3.26,2.34 respectively,all P<0.05).Conclusions Metabolomics distinguish model has a good ability to distinguish PE group,P group and Normal group.Serum characteristic metabolites can successfully reflect the status of fat,calcium and phosphorus metabolism of preeclampsia patients and provide high value for prediction,diagnosis and treatment.

Objective To observe the effect of drug pairs of extracts from Rhizoma Chuanxiong(RC)and Radix Paeoniae Rubra(RPR)in different proportions on promoting blood circulation and removing blood stasis in rats and to find the optimal proportion between the two extracts.Methods The Wistar rat models of blood stasis were established by injection of adrenalin.The changes of the platelet aggregation and adhesiveness and erythrocyte aggregation were observed.Results Blood vessel contraction increased,the platelet aggregation and erythrocyte aggregation increased,erythrocyte deformation occurred and the blood viscosity increased in the model rats.The drug pairs could reduce blood viscosity,ameliorate erythrocyte ability of deformation,reduce erythrocyte aggregation and inhibit platelet aggregation.The effects were obvious especially in the groups of RC and RPR in the proportions of 0.45 g to 0.45 g,0.21 g to 0.45 g.Conclusion The drug couples from RC and RPR in different proportions could improve the blood rheology,the effect being obvious in the groups of RC and RPR in the proportions of 0.45 g to 0.45 g,0.21 g to 0.45 g.

This study was aimed to optimize the uniform design for effective constituents in water-soluble extractives D, E, F of traditional Chinese medicine (TCM) in Qi-Xue Bing-Zhi Fang (QXBZF) for the further validation of the ratio of different compatibility. A total of 100 SD rats were used in the study. Among them, 90 rats were given high fat feeding for 7 days. Then, stratified randomization was used. The rats were divided into the all-party group; D, E original prescription group; D, E optimized compatible group; D, E between optimized and original group; D, E optimized but anti-compatibility group; all-party group adding F; optimized compatible group adding F; QXBZF with mainly paeoniflorin accounted for 49.12% as component D, total flavonoids accounted for 30.0% as component E, total acids accounted for 32.07% in component F; the positive drug control group (Xue-Zhi-Kang, 0.108 g/kg); and the high fat model group. In addition, a blank control group (with normal diet) was set. Each group was treated with gastric perfusion according to drug compatibility proportion for 14 days. Rats were sacrificed to take blood samples for the detection of serum lipid, platelet aggregation, vasoactive substance, and inflammation level. The results showed that compared with the model group, the QXBZF D, E original prescription group and D, E optimized compatible group had significant decreasing effects on TC (P< 0.05). The lowest level of TC decreased by optimized compatible group was (3.49 ± 0.86) mmol/L. The all-party group, D, E original prescription group and optimized compatible group can inhibit the platelet with maximum aggregation rate effectively(P< 0.05, P< 0.01); while the D, E optimized but anti-compatibility group (with D, E inverse proportion) had no effect on it. All-party group and the D, E original group adding F had significant inhibition on IL-6 and IL-8 (P < 0.05, P < 0.01). The D, E original prescription group, D, E optimized compatible group and D, E between optimized and original group can ascend 6-Keto-PGF1α significantly (P< 0.05). ET-1 was decreased in the D, E optimized compatible group (P< 0.05). Other groups had no obvious effect on vascular active substances. It was concluded that different effects between the QXBZF D, E original prescription group and the D, E optimized compatible group were observed in action segment and strength. When F parts added, inhibitions of inflammation levels were enhanced at certain level.

OBJECTIVE: To investigate whether the water extractives of regulating qi and blood prescription (WQBP) had effects on early atherosclerosis of apolipoprotein E-deficient mice (ApoE-mice) at the age of 19 weeks or not, and to explore the possible mechanisms. METHODS: Forty ApoE-mice, six weeks of age, were given high-fat diet and randomly divided into four groups: high-dose WQBP-treated group (360 mg/kg), low-dose WQBP-treated group (72 mg/kg), simvastatin-treated group (25 mg/kg) and untreated group, with ten mice in each group. Meanwhile, ten C57BL/6 mice of same genetic background were allocated to normal control group. Mice in the high- and low-dose WQBP-treated groups and simvastatin-treated group were administered with corresponding drugs from the 15 to 19 weeks. Mice in the untreated and normal control groups were administered with isovolumic water. Sacrificed at 19 weeks, the level of blood-lipid, the plaque construction, plaque integral, and the contents of plaque macrophages and vessel smooth muscle cells of the mice were analyzed by immunohistochemical method and a computer picture processing system. RESULTS: Compared to the untreated group, high-dose WQBP group could obviously decrease the level of low-density lipoprotein cholesterol (LDL-C). Simvastatin group could decrease the levels of LDL-C and total cholesterol (TC) (P<0.01). In high-dose WQBP-treated group and simvastatin-treated group, the thickness of fiber cap and the quantities of vessel smooth muscle cells increased (P<0.05), the quantities of plaque macrophages and the ratio of lipid and plaque reduced (P<0.01). CONCLUSION: WQBP and simvastatin can interfere in early atherosclerosis of ApoE-mice, attenuate and stabilize plaque in some extent. The mechanisms may include adjusting blood lipid, decreasing macrophage number and increasing the quantities of vessel smooth muscle cells.

Objective: To analyze the comparability of different detection systems and methods for tumor markers (TM) by reviewing the results of TM external quality assessment (EQA) in Shandong province during 2015 and 2017. Methods: The results of TM EQA from the Shandong Provincial Clinical Laboratory Center during 2015 and 2017 were collected, and grouped by the detection system or method. After outliers were removed by the CLInet EQA software, the mean and coefficient of variation (CV) in each group were calculated with median as the target value. The difference of TM results in different detection systems were compared by the Kruskal-Wallis H test. Results: Taking alpha-fetoprotein (AFP) as an example, the average CV of different detection methods of TM EQA during 2015 and 2017 ranged from small to large in order of microparticle enzyme immunoassay, electrochemiluminescence, acridine ester chemiluminescence and chemiluminescence. The trends of CV of the other tumor markers were similar to AFP. The average CV of individual marker in electrochemiluminescence group was lower than that in microparticle enzyme immunoassay group. The intra-group CVs of imported detection systems such as Roche, Beckman etc. were relatively ideal, and the average CVs of most tumor markers were less than 10%. However, the intra-group CVs of domestic detection systems such as Shenzhen Snibe, Zhengzhou Autobio etc. were not ideal, and the average CVs of most tumor markers were more than 10%. The target values of different detection systems varied with different items and batches, and there were great variation in carbohydrate antigen (CA) series. Conclusion The results of TM detected by the same automatic detection system are comparable. However, the results of TM detected by most different detection systems and methods are not comparable.

Objective To establish the GIOP model and extract BMSCs from the rat model.We aim to in-vesitigatethe effect ofrhPTH(1-34)for inhibiting β-catenin ubiquitination when combining with Micro-CT and bio-logical technology.We also investigate the influence of rhPTH(1-34)on the GIOP.Methods Female SPF emale rats wererandomly divided into normal control group,methylprednisolone group(model group),methylpredniso-lone+saline group(blankcontrol group)and methylprednisolone+rhPTH(1-34)group(test group). The proximal femoral cancellous bone was examined by Micro-CTand histopathological Staining. The expression of Wnt10b and β-catenin protein were detected. By comparing with inducedBMP-2,BMSCs were treated withrhPTH(1-34)and stained with ALP and alizarin red.Results(1)In Micro-CT,BV/TV,Tb.Th and Tb/N decreased,whereas Tb/sp increased in the test group comparedwith model group(P<0.05).ROI three-dimensional reconstruction of trabecu-lar bone in test group showed local bone repair;(2)Wnt10b and β-cateninexpression increased in the test group compared with the model model(P<0.05),indicating that rhPTH(1-34)can enhance the transcriptional activity of β-catenin(P<0.05)and promote the expression of Wnt10b andβ-catenin(P<0.05).Conclusion The inter-vention with rhPTH(1-34)can prevent GIOP by regulating the Wnt/β-catenin signaling pathway and inhibiting GIOP progress,which can improve the microstructure of bone.

Objective: To evaluate the efficacy and safety of drug-coated balloons (DCB) for de novo large coronary vessels. Methods: One hundred and two patients were retrospectively enrolled in this study, there were 104 lesions with the reference lumen diameter of target vessel more than 2.8 mm and patients were treated with DCB in de novo lesions during May 2015 and July 2017 in our center. Coronary artery angiography and quantitative coronary angiography were performed in 82 (80.4%) patients at follow up period ((8.1±1.7) months post procedure). The endpoints were late lumen loss (LLL) at follow up,and major adverse cardiac events (MACE) including cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and stent or target lesion thrombosis at 12 months post procedure. Results: Ninety-eight lesions were treated with DCB only, 6 (5.9%) bailout drug-eluting stent (DES) were used because of severe coronary dissection, 2 patients (2.0%) received revascularization driven by acute ischemic events during hospitalization. Cutting balloons and NSE balloons were used in 65.4% (68/104) and 26.0% (27/104) lesions. The lesion length was (12.57±3.58) mm and the DCB length was (19.87±4.55) mm. The late lumen loss was (0.01±0.52) mm during angiographic follow up. The TLR rate and overall MACE rate was 3.9% (4/102) and 3.9% (4/102) and there was no death,MI and target lesion thrombosis at 12 months follow up. Conclusion DCB treatment for de novo large coronary vessels is effective and safe.

Objective:To evaluate the pathological features of a heart failure with preserved ejection fraction(HFpEF) model, which is established by spontaneously hypertensive rats (SHR) through high-fat diet and diabetic factors.Methods:Twenty specific pathogen-free grade(SPF grade) and 14-week-old SHR rats were randomly divided into SHR group (normal diet) and HFpEF group [high-fat diet combined with intraperitoneal injection of streptozotocin (STZ, 25 mg/kg) were used to create a diabetic complex model] with 10 rats in each group. Ten SPF and 14-week-old WKY rats with the same genetic background were set as blank control group (WKY group). All rats were fed for 8 weeks. Echocardiography was performed to measure cardiac parameters: peak velocity of early diastolic mitral inflow(E), peak velocity of late diastolic mitral inflow(A), and the early diastolic mitral annulus e′ in the same cardiac cycle, left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), left atrial diameter, right atrial diameter and interventricular septal thickness(IVST). Serological testing included glucose (GLU) and glycosylated serum protein (GSP); Enzyme-linked immunoassay (ELISA) testing included insulin (INS), glucagon (PG), C-peptide (CP), leptin (LEP), atrial natriuretic peptide (ANP) and B-type brain natriuretic peptide (BNP). The rat heart tissue was stained with HE, and the morphological changes of atrial/ventricular tissue were observed under an optical microscope.Results:The pathological characteristics of HFpEF was established in SHR rats fed with high fat and diabetes. Echocardiography showed that compared with the WKY group, the values of E, E/A and E/e′ in the HFpEF group were significantly increased (all P<0.01), and e′and LAEF were significantly reduced (all P<0.01). In the HFpEF group, the anteroposterior and tranverse dimensions of the left atrium and the long-axis dimension of the right atrium increased to varying degrees (all P<0.05), and the IVST was also significantly increased ( P<0.01). At the same time, atrial wall was thickened obviously, myocardial cells were disordered, and myocardial fibers were broken. Compared with the WKY group, the levels of serum markers ANP and BNP in HFpEF group were significantly increased (all P<0.01), and the levels of serum insulin-related indicators INS, PG, CP, LEP, GSP, and GLU increased to varying degrees (all P<0.01). Conclusions:The composite model established by SHR rats through high-fat diet and diabetic factors can simulate the Doppler echocardiographic changes and pathological features of HFpEF, as well as abnormal changes in serum related markers and insulin indicators.

ObjectiveTo explore the material basis and molecular mechanism of Linggui Qihua prescription （LGQH） against myocardial fibrosis in heart failure with preserved ejection fraction （HFpEF）. MethodLiquid chromatography-mass spectrometry （LC-MS） was used to qualitatively analyze the active components of LGQH. AutoDock software was employed for molecular docking between the active components of LGQH and target proteins including α-smooth muscle actin （α-SMA）， type Ⅰ collagen （ColⅠ）， type Ⅲ collagen （ColⅢ）， matrix metalloproteinase-9 （MMP-9）， and tissue inhibitor of metalloproteinase-1 （TIMP-1）. In vivo experiments were conducted on 40 spontaneously hypertensive rats （SHRs） aged 4 weeks， which were divided into an HFpEF group， an Entresto group （0.018 g·kg^-1）， and low- and high-dose LGQH groups （3.87， 7.74 g·kg^-1）. A high-fat， high-salt， and high-sugar diet was administered for 16 weeks along with intraperitoneal injection of streptozotocin solution for 8 weeks to establish an HFpEF model in rats. The blank group consisted of 10 Wistar Kyoto （WKY） rats and 10 SHRs. After successful modeling， the WKY， SHR， and HFpEF groups were given equal volumes of normal saline， while the other three groups received predetermined interventions. Daily oral gavage was performed for 6 weeks. After intervention， echocardiography was conducted to measure left ventricular （LV） anterior wall thickness （LVAWd）， LV posterior wall thickness （LVPWd）， LV internal diameter at end-diastole （LVIDd）， LV ejection fraction （LVEF）， isovolumic relaxation time （IVRT）， early diastolic peak velocity of mitral valve inflow （E）， and early diastolic mitral annular velocity （e'）. The E/e' ratio was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum atrial natriuretic peptide （ANP）， B-type natriuretic peptide （BNP）， and galectin-3 （Gal-3）. Myocardial fibrosis was observed through Masson staining of pathological sections， and collagen volume fraction （CVF） and perivascular fibrosis ratio （PFR） were calculated. Real-time polymerase chain reaction （PCR） and Western blot were employed to detect LV myocardial mRNA and protein expression of α-SMA， ColⅠ， ColⅢ， MMP-9， and TIMP-1. ResultLC-MS identified 13 active components in LGQH. Molecular docking indicated stable binding of the 13 compounds with five target proteins. In vivo experiments showed that compared with the blank group， the HFpEF group had significantly increased LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR. LV myocardial α-SMA， ColⅠ， and ColⅢ mRNA and protein expression was significantly upregulated， while MMP-9/TIMP-1 mRNA and protein ratios were significantly downregulated （P<0.05， P<0.01）. Compared with the HFpEF group， LGQH might dose-dependently reduce LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR， downregulated myocardial α-SMA， ColⅠ， ColⅢ mRNA expression， α-SMA， and ColⅠ protein expression， and upregulated MMP-9/TIMP-1 mRNA and protein expression （P<0.05， P<0.01）. ConclusionLGQH contains multiple active components and may inhibit myocardial fibrosis in HFpEF rats. It may further alleviate LV hypertrophy， dilation， and diastolic dysfunction， making it an effective Chinese medicinal prescription for treating HFpEF.