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.

Objective To investigate causes and treatments for a fracture of the contralateral femoral neck in the elderly with prosthetic replacement for femoral neck fractures.Methods A retrospective analysis was conducted on 85 cases undergone prosthetic replacement for femoral neck fractures between March 2005 and May 2012,including 12 cases in secondary replacement group due to fractures of the contralateral uninjured femoral neck after primary prosthetic replacement and 73 cases in primary replacement group.Variables were compared between the two groups including causes of injury,age,sex,bone density,complications,quality of life,Harris score of the contralateral hip joint,surgical choice.Refracture reasons were evaluated and treatment plans were proposed.Results Immediate cause of injury in all cases was falling.Primary and secondary replacement groups showed mean age of (68.82 ± 5.18) yearsvs (76.83 ± 3.64) years (P＜0.05),male to female ratio of 0.66:1 vs 0.09:1 (P＜0.05),and bone mineral density of (0.507 ± 0.062) g/cm2 vs (0.461 ± 0.095) g/cm2(P ＜0.05).Moreover,cases in the two groups suffered from the associated complications (hypertension,diabetes mellitus,cataract,stroke,rheumatoid arthritis,and Parkinson' s disease).Except for the diabetes mellitus,incidence of the other five basic diseases presented significance differences between the two groups (P ＜ 0.05).Of primary and secondary replacement groups,quality of life was (76.26 ±14.17) points vs (67.86 ± 16.74) points (P ＜ 0.05) ; Harris score of the contralateral hip was (98.66 ±1.39) points vs (90.75 ± 5.39) points (P ＜ O.05).For treatment choice,32 total hip arthroplasty (THA) and 41 femoral head arthroplasty (FHA) with cement fixation in 44 cases and cementless fixation in 29 cases were performed in primary replacement group; two total hip arthroplasty and 10 femoral head arthroplasty with cement fixation in 11 cases and cementless fixation in one were performed in secondary placement group (P ＜ 0.05).Conclusions Fall remains the immediate cause of the contralateral fractures following prosthetic replacement of femoral neck fractures in the elderly.Aging,females,bone density reduction,high-incidence of complications,decreased quality of life,and joint function impairment after the primary prosthetic replacement are unfavorable factors.Prosthetic replacement is still the preferred choice of treatment and surgical procedure is more likely to be the simple cemented FHA.

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.

Establishing an efficacy evaluation system that conforms to the laws of traditional Chinese medicine （TCM） is one of the keys in the development of TCM. With certain progress in recent years， however， the clinical efficacy evaluation systems or consensus that has been formed are not widely adopted. The main reason is the lack of objectification and standardization of efficacy evaluation， and additionally fixed efficacy evaluation system cannot meet the needs of different clinical research purposes. This paper initially analyzed the development status of clinical efficacy evaluation of heart failure （HF）， and then discussed the specific methods， advantages and difficulties in constructing a TCM clinical efficacy evaluation system for HF using the 1+N model， guided by the idea of combining traditional Chinese and western medicine， disease and syndrome， and based on the shared reported clinical outcomes by doctors and patients. Establishing an efficacy evaluation system that combines disease and syndrome can build a bridge to connect TCM with western medicine； the shared reported clinical outcomes by doctors and patients can reflect the people-centered concept and holism concept in TCM； the 1+N efficacy evaluation model can meet the general clinical research need by constructing one core outcome set （“1”）， and can match different research purposes by adding numbers of other outcomes （“N”）. One difficulty in constructing the TCM efficacy evaluation system for HF is to unify the differentiation standard for TCM syndromes of HF and the standardization to diagnose HF firstly， and then distinguish between syndrome efficacy standards and syndrome diagnostic standards. By constructing a 1+N model-based efficacy evaluation system for HF that not only conforms to the characteristics of TCM itself but also embodies the evidence-based medicine concept in western medicine， it is expected to provide ideas for evaluating clinical efficacy of TCM.

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.

Objective:To investigate whether Lycopi Herba can serve as a viable alternative to Alismatis Rhizoma in the treatment of heart failure (HF) through network pharmacology and molecular docking techniques.Methods:TCMSP database was used to filter active components of Lycopi Herba and Alismatis Rhizoma. SwissTargetPrediction database was used to predict potential targets. HF-related targets were collected from databases such as GeneCards, OMIM, and DisGeNET. Venny 2.1.0 was used to draw a Venn diagram illustrating the intersection of targets between Lycopi Herba and Alismatis Rhizoma and HF. A protein-protein interaction (PPI) network was established using the String database, and key targets for the treatment of HF with Lycopi Herba and Alismatis Rhizoma were selected using Cytoscape 3.9.1 software to construct a component-intersection target network. The intersection targets were then analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using Metascape. Molecular docking techniques were used to evaluate the affinity between active components and key targets.Results:Lycopi Herba primarily targeted pivotal proteins such as HMGCR and CYP27B1, while Alismatis Rhizoma had a broader target spectrum, including PPARA, JAK2, among others. Shared key targets between the two included HMGCR and ESR1, which were primarily involved in cholesterol synthesis and steroid hormone biosynthesis. Enrichment pathway analysis showed similarities in steroid metabolism between the two; Alismatis Rhizoma, however, was more likely to act through protein phosphorylation regulation and modulating the PI3K-Akt signaling pathway for HF treatment. A unique target for Lycopi Herba in treating HF was CHRM4, indicating its potential for blood pressure regulation and myocardial protection.Conclusions:Both Lycopi Herba and Alismatis Rhizoma exhibit certain commonalities in the treatment of HF, but Alismatis Rhizoma has a wider range of targets and signaling pathways, implying more extensive therapeutic potential. However, considering the nephrotoxicity of Alismatis Rhizoma, Lycopi Herba could be considered as an alternative treatment for HF, especially in patients with renal insufficiency or in the early stages of HF.

Objective To evaluate the characteristics of a rat model of heart failure with a preserved ejection fraction(HFpEF)induced by combined factors,and to investigate the correlation of myocardial strain parameters to myocardial hypertrophy and fibrosis.Methods Eight WKY rats and eight spontaneously hypertensive rats(SHR)served as control groups and were fed normal feed until the end of the experiment.Thirty-two SHR rats were equally divided into SHR+S,SHR+F,SHR+SF,and SHR+Combined groups,and fed high-salt,high-fat,high-salt-fat,or high-salt-fat-sugar feed,respectively,in combination with intraperitoneal injection of streptozotocin for 30 weeks.After modeling,the heart weight/body weight(HW/BW)ratio,systolic blood pressure(SBP),and diastolic blood pressure(DBP)were measured.Echocardiography was performed to measure the left ventricular(LV)end-diastolic internal diameter(LVIDd),LV anterior wall thickness(LVAWd),LV posterior wall thickness(LVPWd),LV ejection fraction(LVEF),isovolumetric diastolic time(IVRT),and peak early diastolic passive filling velocity(E)/early diastolic mitral annular velocity(e').Speckle tracking echocardiography was conducted to determine the global longitudinal strain(GLS)and strain rate(GLSr),global radial strain(GRS)and strain rate(GRSr),as well as the global circumferential strain(GCS)and strain rate(GCSr).Serum was collected and analyzed for triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),glucose(GLU),and glycated serum protein(GSP).ELISA were used to measure serum B-type brain natriuretic peptide(BNP),angiotensin Ⅱ(AngⅡ),and galectin-3(Gal-3).Myocardial tissue was subjected to HE and Masson staining for cardiomyocytes and myocardial fibrosis,and the cardiomyocyte cross-sectional area(CSA)and collagen volume fraction(CVF)were calculated.Additionally,the correlation of myocardial strain parameters to CSA and CVF was analyzed.Results Compared with the control group,in model groups,especially the SHR+combined group,HW/BW,SBP,DBP,serum indexes(TC,TG,LDL-C,GLU,GSP,BNP,AngⅡ,and Gal-3)and echocardiographic parameters(LVIDd,LVAWd,LVPWd,IVRT,and E/e')were significantly up-regulated.Absolute values of speckle-tracking echocardiographic parameters(GLS,GLSr,GRS,GRSr,GCS,and GCSr)were decreased considerably.HE and Masson staining of myocardial tissues suggested marked cardiomyocyte hypertrophy and fibrosis,and significant increases were observed in CSA and CVF(P＜0.05).Correlation analysis showed that GLSr,GCS,and GCSr were strongly linked to CSA,and GLS,GLSr,and GCSr were strongly linked to CVF(P＜0.01).Conclusions A rat model of HFpEF induced by hypertension and dysregulation of glucolipid metabolism replicated the basic characteristics of HFpEF in terms of etiology,clinical features,and myocardial pathological changes,and might be a reliable animal model of metabolic syndrome-related HFpEF.Moreover,myocardial strain indices were closely related to myocardial hypertrophy and fibrosis and might indirectly reflect subtle myocardial lesions and dysfunction.

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.