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.

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.

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.

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 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 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 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 explore the therapeutic effect of drinking water test combined with swallowing training on cerebral infarction patients with dysphagia.Methods A total of 68 cerebral infarction patients with dysphagia in our department were randomly divided into observation group and control group.The control group was given routine nursing,while the observation group was given drinking water test to guide diet,and systemic swallowing function training on the basis of the control group.The therapeutic effects,feeding conditions and VSD scale scores were compared after 1 month of intervention between the two groups.Results The drinking water test score in the observation group was lower than that in the control group,and the total effective rate of the swallowing function improvement was higher than that in the control group,the differences were statistically significant (P ＜ 0.05).The FOIS score in the observation group was higher,and the score of VSD scale was lower than that in the control group,the differences were statistically significant (P ＜ 0.05).Conclusion Drinking water test combined with swallowing training can effectively improve the swallowing function of patients with dysphagia after cerebral infarction,and is beneficial to the normal diet of the patients.

Objective To explore the therapeutic effect of drinking water test combined with swallowing training on cerebral infarction patients with dysphagia.Methods A total of 68 cerebral infarction patients with dysphagia in our department were randomly divided into observation group and control group.The control group was given routine nursing,while the observation group was given drinking water test to guide diet,and systemic swallowing function training on the basis of the control group.The therapeutic effects,feeding conditions and VSD scale scores were compared after 1 month of intervention between the two groups.Results The drinking water test score in the observation group was lower than that in the control group,and the total effective rate of the swallowing function improvement was higher than that in the control group,the differences were statistically significant (P ＜ 0.05).The FOIS score in the observation group was higher,and the score of VSD scale was lower than that in the control group,the differences were statistically significant (P ＜ 0.05).Conclusion Drinking water test combined with swallowing training can effectively improve the swallowing function of patients with dysphagia after cerebral infarction,and is beneficial to the normal diet of the patients.