10.3969/j.issn.2095-4344.2013.25.007

ObjectiveTo determine the feasibility of using left ventricular volume-time curve in the evaluation of left ventricular diastolic function,and to analyze characteristics of left ventricular volume-time curve changcs in hypertrophic cardiomyopathy (HCM).MethodsSeventeen cases of HCM and 12 healthy volunteers received cardiac MRI (CMRI) examination,and left ventricular (LV) 2-chamber long and short axis cine imaging were performed,LV volume-time curves were reconstructed and platform time,different diastolic volume recovery (DVR) time and their corresponding filling velocity were calculated from LV volume-time curve off-line.The DVR time and their corresponding filling velocity were analyzed by using multiple linear regression analysis. Results Compared with the group of healthy volunteers,ventricular septal HCM group had delayed left ventricular 50％,70％ DVR time[ (8.9 ± 1.3) versus (7.7 ± 0.8 ) phase,F=6.787,P=0.016;(11.3 ±1.6) versus(9.7±1.8) phase,F=4.927,P=0.036] and shortened plateau time [ ( 1.8 ± 1.7) versus ( 4.1 ± 1.4 ) phase,t =6.787,P ＜ 0.01 ].Ventricular septal HCM group had reduced 30％,50％ DVR filling rates [ (0.22 ± 0.11 ) versus (0.40 ± 0.15 ) ml/ms,F =12.916,P ＜ 0.01 ; (0.20 ± 0.09 ) versus (0.30 ± 0.10) ml/ms,F =7.121,P =0.014 ] compared with those in the group of healthy volunteers.But 70％,80％,90％ DVR filling rates showed no statistically significant different in the two groups.In HCM patients,myocardial fibrosis caused 50％,70％,80％ DVR time delay [ (9.6 ± 1.0) versus ( 7.9 ± 1.5 ) phase,F =5.000,P =0.045 ; ( 12.3 ± 1.4 ) versus ( 9.6 ± 1.8)phase,F=8.039,P=0.015;(13.1 ±1.4 ) versus(10.9±1.9)phase,F=5.060,P=0.044],but no significant difference of DVR filling rate was found between the two groups. Conclusions Left ventricular volume curve analysis techniques can be used for detailed evaluation of left ventricular diastolic function.The left ventricular diastolic dysfunction of hypertrophic cardiomyopathy occurs mainly in early diastolic period,and accompanied by the shortening of the plateau time. Myocardial fibrosis can aggravate early left ventricular diastolic dysfunction of hypertrophic cardiomyopathy.

Objective To investigate the effects of a new c-Met inhibitor SU11274 on apoptosis and motility of c-Met-positive basal-like breast cancer cells MDA-MB-231. Methods The concentrations of SUl1274 were set to 0,0.1,1,10 and 20 μmol/L.Morphological change of apoptotic cells was analyzed by Hoechst33342,MitroTrackerRed and Yo-pro-1 staining.The apoptotic rate of MDA-MB-231 cells were determined by Annexin V/PI double-staining. The expression of apoptosis related proteins (Bcl-XL,Caspase-3 and PARP) and phosphorylation levels of c-Met and Akt were analyzed by Western blot.The capability of motility were measured by wound-healing assay and chemotaxis assay. Results After treatment by SU11274( 10 μmol/L) for 48 h,shrinking apoptotic cells of MDA-MB-231 was observed by flurescent microscope and nuclear fragmentation was seen.Annexin V/PI double-staining showed SU11274induced apoptosis of MDA-MB-231 cells (P ＜ 0.05 ),and the apoptotic rates were (7.3 ± 0.9) ％,( 14.1 ±0.6) ％,(35.5 ± 4.4) ％ and (48.2 ± 5.3 ) ％,respectively.SU11274 downregulated the expression of Bcl-XL and promoted the dissection of Caspase-3 and PARP in a dose dependent relationship.SU11274 prolongs the wound-healing time,decreases the migration cell count (P ＜ 0.05 ) and effectively inhibits the phosphorylation of c-Met and its downstream key proteins Akt in a dose-dependent manner.Conclusions C-Met inhibitor SU11274 induces apoptosis and inhibits the motility of c-Met-positive basallike breast cancer cell line MDA-MB-231,probably through inhibiting phosphorylation of c-Met/PI3K/Akt.

Objective To retrospectively analyze the relationship between progression free survival (PFS) and overall survival (OS) in patients with non small cell lung cancer (NSCLC), and to detect the influence of plasma fibrinogen and D-dimer levels before treatment in the prognosis of advanced stage (stageⅢB-Ⅳ) of NSCLC. Methods The study comprised 134 NSCLC patients with clear pathological diagnosis. All patients were grouped by plasma fibrinogen and D-dimer levels before treatment. We set the normal values of fibrinogen as≤4 g/L and D-dimer as≤500μg/L(FEU). Patients with normal levels of fibrinogen and D-dimer were grouped into low risk group, patients with elevated fibrinogen or D-dimer were grouped into median risk group, and patients with both elevated values were grouped into high risk group. Chi-square test and one way ANOVA analysis were used to analyze the clinicopathologic features of different groups. The OS and PFS in different groups were analyzed by Kaplan-Meier analysis. Univariate analysis of PFS and OS were conducted. Then multivariate analysis was conducted with the Cox regression model in three groups. Results The clinicopathologic features showed no differences between different groups. There were significant differences in OS and PFS between high risk group and other groups. In the survival curves, the high risk group showed poor prognosis. The result of multivariate analysis showed that clinical stage (OS:RR=1.846, 95%CI 1.150-2.964,P=0.011; PFS:RR=1.762, 95%CI 1.190-2.609, P=0.005) and grouped by fibrinogen and D-dimer (OS:RR=1.415,95%CI 1.050-1.908,P=0.023;PFS:RR=1.373,95%CI 1.070-1.761,P=0.013) were prognostic factors for patients with NSCLC. Conclusion The plasma fibrinogen and D-dimer levels before treatment are closely related with the prognosis of NSCLC patients. And a high plasma fibrinogen and D-dimer levels before treatment are associated with poor prognosis in advanced stage of NSCLC patients.

[Objective]Based on data mining,network pharmacology and molecular docking technology,to explore the rule and mechanism of Chinese medicine in the treatment of chronic viral hepatitis B.[Methods]Clinical research literature on Chinese medicine treatment of chronic viral hepatitis B collected in China National Knowledge Internet(CNKI),Wanfang Database and VIP Database from establishment to September 12,2022,were searched,and the data were standardized and classified.Meanwhile,Excel 2019,Cytoscape 3.8.0 and Qrigin 2021 software were used to analyze the frequency,association rules and systematic clustering of the Chinese medicine compounds meeting the inclusion criteria,and obtain medication rules and core prescriptions.The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),Human Gene database(GeneCards)and Online Human Mendelian Inheritance in Man(OMIM)database were used to obtain core prescription active ingredients,therapeutic targets and disease-related targets,respectively.The STRING 11.5 database and Cytoscape 3.8.0 software were used for network visualization,and the Metascape database was used for gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,AutoDock Vina 1.2.3 software were used for molecular docking.[Results]A total of 192 prescriptions were included,including 225 drugs.The drug properties were cold,warm and normal,and the drug flavors were bitter,sweet and acrid,mostly attributed to liver,lung,stomach and spleen channels.The main types of action were deficiency tonic,heat-clearing,diuretic and dehydrating.Association analysis showed that the common compatibility was Atractylodes macrocephala-Curcumae radix-Poria cocos-Salvia miltiorrhiza,Atractylodes macrocephala-Curcumae radix-Poria cocos,Astragalus membranaceus-Phyllanthus urinaria-Salvia miltiorrhiza.The clustering analysis was divided into 4 categories,and the clustering effect was good.Network pharmacology and molecular docking suggested 201 kinds of active ingredients,4 208 targets,2 920 disease targets,104 overlapping targets of drug diseases,and 1 369 biological processes(BP),celluar component(CC)87,molecular function(MF)120 were identified by GO functional enrichment analysis,and KEGG pathway enrichment analysis identified 190 pathways,the conformation of the core components and core target molecular bonding results tended to be stable.[Conclusion]By using literature data mining,network pharmacology and molecular docking technology,the drug use rules and core formulations of traditional Chinese medicine in the treatment of chronic viral hepatitis B were summarized,and the potential therapeutic targets and signaling pathways of the core formulations in the intervention of chronic viral hepatitis B were further explored,and the molecular docking results were good,which could provide ideas and methods for the future research of chronic viral hepatitis B.

BACKGROUND:Several observational studies have found a close relationship between thyroid function levels and sarcopenia,but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE:To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS:A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin,free triiodothyronine,free tetraiodothyronine,subclinical hyperthyroidism,subclinical hypothyroidism,and four related phenotypes of sarcopenia-lefthand grip strength,right hand grip strength,limb lean mass,and gait speed.The inverse-variance weighted method,weighted median method,simple mode method,weighted median estimator method,and MR Egger regression method were used as analysis methods,while heterogeneity test,pleiotropy test,MR-PRESSO,leave-one-out method,funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION:Elevated levels of thyroid-stimulating hormone increased left-(β=0.02,SE=0.01,P=0.01)and right-handed grip strength(β=0.02,SE=0.01,P=0.01),an increase in free triiodothyronine decreased left-(β=-0.06,SE=0.02,P=9.5×10-5)and right-handed grip strength(β=-0.07,SE=0.02,P=9.3×10-5),and subclinical hyperthyroidism decreased gait speed(β=-4.4×10-3,SE=1.7×10-3,P=0.01).The sensitivity analysis results were basically consistent with the main analysis results.To conclude,an increase in thyroid-stimulating hormone is a protective factor for sarcopenia,and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia.

Objective:To investigate the pathogenic genes, clinical features and treatment as well as follow-up of children with congenital long QT syndrome (LQTS).Methods:The clinical data, genetic test results and follow-up data of 16 congenital LQTS children with syncope as the first manifestation admitted to the Department of Cardiology, Beijing Children′s Hospital Affiliated to Capital Medical University from August 2016 to March 2023 were collected and retrospectively analyzed.Results:Among the 16 LQTS patients, the age of first syncope onset was 1.3-13.3 (7.37±3.41) years, and the interval between first syncope onset and clinical diagnosis was 0-48 (14.8±16.2) months.A total of 13 (81.3%) patients had triggers of syncope, of which nine were exercise-induced and four were emotional induced.Genetic testing was performed in 13 patients with LQTS, of which 12 (92.3%) were found to have pathogenic or suspected pathogenic mutations from KCNQ1, KCNH2, and SCN5A gene.The corrected QT interval of 16 patients was (550.0±50.2) ms, all cases≥460 ms.Schwartz scored 6.0 (5.0, 6.0) points, all cases≥4 points.All patients were initially treated with metoprolol or propranolol, of which 14 patients were followed up to date, three patients had recurrent syncope, and five patients stopped taking the medicines by themselves.One patient with high-dose metoprolol (LQT2) was treated with mexiletine after recurrent episodes.One patient who was intolerant to high-dose propranolol underwent left cardiac sympathectomy and was followed up after surgery without syncope episodes.None of the patients underwent implantable cardioverter defibrillator implantation. Conclusion:Children with LQTS and syncope symptoms have high positive rate of genetic tests.The genetic results could assist typing of patients with LQTS and guide treatment.Routine electrocardiogram screening in children with syncope may diagnose LQTS earlier and reduce misdiagnosis and missed diagnosis.β-blockers are the cornerstone of treatment for patients with LQTS.Strengthening follow-up management and improving patients′ treatment compliance is conducive to further improving the treatment response rate of patients.

Objective To investigate the diagnostic efficiency of patients with human epidermal growth factor receptor-2(HER-2)over expressed breast cancer via combining the dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)perfusion parameters,apparent diffusion coefficient(ADC)value and clinical feature model.Methods A total of 197 breast cancer patients who underwent DCE-MRI and diffusion weighted imaging(DWI)scans were analyzed retrospectively,including 47 breast cancer patients with HER-2 over expressed and 150 breast cancer patients with non-HER-2 over expressed.The t-test or chi-square test was used to compare the DCE-MRI perfusion parameters[Ktrans,Kep,Ve,W-in,W-out,and time to peak(TTP)],ADC value,and clinical feature between the two groups.The diagnostic efficiency of the models were analyzed via receiver operating characteristic(ROC)curves.Results There were significant difference in the maximum tumor diameter,minimum tumor diameter,T stage,N stage,Kep,W-in,and ADC value between HER-2 over expressed breast cancer and non-HER-2 over expressed breast cancer groups(P＜0.05).The proposed combined model,which included the combined maximum tumor diameter,minimum tumor diameter,T stage,N stage,Kep,W-in,and ADC value,showed a better diagnostic efficiency with area under the curve(AUC)(AUC=0.763)than the clinical model(AUC=0.634)based on the combined maximum tumor diameter,minimum tumor diameter,T stage,and N stage,and the imaging model(AUC=0.715)based on the combined Kep,W-in and ADC value.Conclusion The maximum tumor diameter,minimum tumor diameter,T stage,N stage,Kep,W-in,and ADC value may be associated with HER-2 over expressed breast cancer.Combining all above parameters can improve the diagnostic ability of breast cancer patients with HER-2 over expressed.

Objective:To investigate the correlation between the number of circulating DLBCL cell and the marrow tumor cell burden and the prognostic indicators in patients with DLBCL, and to evaluate the feasibility of circulating DLBCL cell reflecting the marrow tumor burden and disease progression. Optimization of FCM for screening circulating DLBCL cell was done to monitor MRD and recurrence.Methods:We conducted a retrospective study in 75 diagnosed DLBCL patients in the First Affiliated Hospital of Zhengzhou University from June 2020 to February 2021, including 43 males and 32 females aged 61 (37-85) years. According to the diagnosis and treatment criteria, the patients were divided into initial and recurrence group ( n = 53), partial response(PR)group ( n=14) and complete response(CR)group ( n=8). According to the positive criteria of circulating DLBCL cells, 48 cases were divided into circulating DLBCL positive group and 27 cases were negative group. 30 anemia patients with non-B-cell tumor-related diseases were selected as the control group, including 16 males and 14 females, aged 52 (30-79) years. 70 healthy subjects, including 36 males and 34 females, aged 39 (25-57), were selected for methodology optimization. FCM was used to detect the ratio of marrow and circulating DLBCL cells in each group, and analyze the connection between circulating DLBCL cells and clinical indicators. Statistical analysis was performed using t test, χ 2 test, Kruskal-Wallis H test, Spearman rank correlation, and Logistic regression. Results:(1) Bone marrow and circulating DLBCL cells were not detected in CR group and control group; The positive rate of circulating DLBCL cells in the initial/recurrent group and PR groups was 75.47% and 57.14%, respectively. The proportion of bone marrow and circulating DLBCL cells was positively correlated in the two groups ( P value was <0.001 and 0.020, respectively). (2) The proportion of bone marrow and circulating DLBCL cells in the initial and recurrent groups, PR group, CR group and control group decreased successively ( P<0.05). The proportion of DLBCL cells was 27.72% (initial and recurrent bone marrow group), 26.92% (initial and recurrent circulating group), 3.23% (bone marrow PR group) and 1.67% (circulating PR group), respectively. (3) Compared with the negative group, the circulating DLBCL cell positive group had increased LDH, β 2-MG, and CMYC expression(≥80%), with decreased LYM, HGB<100 g/L, B symptoms, PD-L1 expression, and age ≥60 years, showing higher ECOG, aaIPI/IPI scores and Ann staging ( P<0.05). Age ≥60, B symptoms, and PD-L1 expression were independent risk factors for circulating DLBCL cells ( P<0.05). Conclusions:The detectable rate of circulating DLBCL cell could be improved by optimizing the preoperative treatment conditions of FCM. Circulating DLBCL cells can reflect the tumor burden and disease progression. Detecting circulating DLBCL cells may improve patients′ compliance.