Measurement of carotid pulse wave velocity using ultrafast ultrasound imaging in hypertensive patients.

PURPOSE: The study aimed to assess the utility of ultrafast ultrasound imaging for evaluation of carotid pulse wave velocity (PWV) in newly diagnosed hypertension patients. METHODS: This prospective non-randomized study enrolled 90 hypertensive patients in our hospital from September to December 2013 as a hypertension group. An age- and sex-matched cohort of 50 healthy adults in our hospital from September to December 2013 was also included in the study as a control group. Carotid PWV at the beginning and at the end of systole (PWV-BS and PWV-ES, respectively) and intima-media thickness (IMT) were measured by ultrafast ultrasound imaging technology. The associations of PWV-BS, PWV-ES, and IMT with hypertension stage were evaluated by Spearman correlation analysis. RESULTS: PWV-BS and PWV-ES in the hypertension group were significantly elevated compared with those in control group. Different hypertension stages significantly differed in PWV-BS and PWV-ES. PWV-BS and PWV-ES appeared to increase with the hypertension stage. Moreover, IMT, PWV-BS, and PWV-ES were positively correlated with the hypertension stage in hypertensive patients. CONCLUSION: Ultrafast ultrasound imaging was a valid and convenient method for the measurement of carotid PWV in hypertensive patients. Ultrafast ultrasound imaging might be recommended as a promising alternative method for early detection of arterial abnormality in clinical practice.

Relationship between blood pressure reverse dipping and type 2 diabetes in hypertensive patients.

Recent studies suggested that nocturnal variations of blood pressure (BP) were closely related to type 2 diabetes. However, little information has been revealed about the relationship between reverse-dipper pattern of BP and type 2 diabetes. In this cross-sectional study, BP variations of 531 hypertensive patients were evaluated with ambulatory BP monitoring (ABPM). Diagnosis of diabetes in Chinese adults was made according to diabetes diagnostic criteria of 2015. Multivariate logistic regression was used to examine the relationships between type 2 diabetes and ABPM results. In the study, patients with reverse-dipper pattern (32.3%) had the highest prevalence of type 2 diabetes compared with dippers (21.4%) and nondippers (23.3%). After multivariate logistic regression, reverse-dipper BP pattern (OR 2.067, P = 0.024) and nondipper BP pattern (OR 1.637, P = 0.039) were found to be correlated with type 2 diabetes compared with dipper pattern. The results of our study also suggested that type 2 diabetes might contribute to the reverse-dipper pattern of BP (OR 1.691, P = 0.023). In addition, fasting glucose was negatively correlated with the decline rate of nocturnal SBP (r = -0.095, P = 0.029). Reverse-dipper pattern of BP in ABPM may be independently associated with type 2 diabetes in patients with hypertension.

[Changes of left ventricular function in cirrhotic patients and their correlation with the model for end-stage liver disease score].

OBJECTIVE: To investigate the changes of left ventricular structure and function in patients with liver cirrhosis and their correlation with the model for end-stage liver disease (MELD) score. METHODS: A total of 89 cirrhotic patients admitted between June, 2012 and June, 2014 and 30 healthy control subjects were enrolled in the study. According to MELD score, the cirrhotic patients were divided into 3 groups with MELD scores ≤9, between 10 and 19, and ≥20. The parameters of the left ventricle in resting state were measured using Doppler echocardiography, including left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left atrial diameter (LAD), ejection fraction (LVEF), cardiac output (CO), mitral flow velocity, and E wave deceleration time (DT), and evaluated their relationship with MELD score. RESULTS: Compared with the control subjects, the cirrhotic patients showed significantly increased LVESD, LVEDD, IVST, LAD, CO and DT but reduced VE/VA ratio (P<0.05 or 0.01). The values of LVESD, LVEDD, IVST, LAD and DT increased gradually with MELD scores (P<0.05 or 0.01). VE/VA ratio was higher in patients with MELD score of 10-19 than in those with MELD score ≤9, and decreased significantly in those with MELD score ≥20. Of the cirrhotic patients, 55% were found to have left atrial enlargement and 44% had a VE/VA ratio ≤1; left atrial enlargement and a VE/VA ratio below 1 were more common in patients with a MELD score ≥20 than in those with lower MELD scores. The LAD, LVEDD and DT were positively correlated with MELD scores (r=0.208, 0.319 and 0.197, respectively; P<0.05 or 0.01). CONCLUSIONS: The patients with liver cirrhosis can have cardiac function deficiency manifested mainly by left ventricular diastolic dysfunction in positive correlation with the severity of liver disease.

Blood pressure reverse-dipping is associated with early formation of carotid plaque in senior hypertensive patients.

Nocturnal variations in blood pressure (BP) were associated with carotid intima-media thickness. However, the precise relationship between circadian variations of BP and carotid plaques remains unknown. Therefore, the prognostic value of reverse-dipper pattern of BP for carotid plaque was investigated. In this cross-sectional study, a total of 524 hypertensive patients were recruited and evaluated with ambulatory BP monitoring between April 2012 and June 2013. Carotid plaque was classified into Grade 0 (normal or no observable plaque), Grade 1 (mild stenosis, 1%-24% narrowing), and Grade 2 (moderate stenosis, ≥25% narrowing). Multinomial logistic regression was applied to analyze the relationship between different degrees of carotid plaque and ambulatory BP monitoring results. Reverse-dipper pattern of BP was more common in older patients, smokers, and those with elevated fasting glucose. The incidences of coronary artery disease, lacunar infarction, and diabetes were also higher among hypertensive with reverse-dipper pattern. Multinomial logistic regression analysis showed that reverse dipper (odds ratio [OR] 2.500; 95% confidence interval [CI] 1.320-4.736; P = 0.005), age (OR 1.089; 95% CI 1.067-1.111; P < 0.001), smoke (OR 1.625; 95% CI 1.009-2.617; P = 0.046), and diabetes (OR 1.759; 95% CI 1.093-2.830; P = 0.020) were significantly different between mild carotid plaque and normal. Our results also suggested that mild carotid plaque was closely related to reverse-dipper pattern of BP (2.308; 95% CI 1.223-4.355; P = 0.010). Reverse-dipper pattern of BP may be a risk factor for carotid atherosclerosis and play a crucial role in the early formation of carotid plaque.

Cirrhosis-related changes in left ventricular function and correlation with the model for end-stage liver disease score.

OBJECTIVE: The purpose of our study is to investigate cirrhosis-related left ventricular remodeling and functional changes, further to analyze the correlations with model for end-stage liver disease (MELD) score. METHODS: A total of 89 cirrhotic patients were enrolled for study and subgrouped according to MELD score: ≤ 9, 10-19, and ≥ 20. Thirty healthy individuals were enrolled as controls. All study participants underwent cardiac assessment of the left ventricle with Doppler echocardiography; the parameters assessed included left ventricular-end systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left atrial diameter (LAD), left ventricular ejection fraction (LVEF), cardiac output (CO), mitral flow velocity (VE/VA ratio), and E-wave deceleration time (DT). RESULTS: The cirrhotic patients had significantly higher LVESD, LVEDD, IVST, LAD, CO and DT than the control group, but significantly lower VE/VA ratio (all P < 0.05). Subgroup analysis showed that the higher the MELD score, the greater the increase in LVESD, LVEDD, IVST, LAD and DT (all P < 0.05). Nearly one-half of the cirrhotic patients showed left atrial enlargement and a VE/VA ratio ≤ 1, and these features were more common in patients with MELD score ≥ 20. LAD, LVEDD and DT were positively correlated with MELD score (r = 0.208, 0.319 and 0.197, respectively; all P < 0.05). CONCLUSIONS: Patients with cirrhosis had impaired cardiac function, mainly present as left ventricular diastolic dysfunction, and the extent of dysfunction was correlated with the MELD score. Left atrial enlargement and VE/VA ratio ≤ 1 may serve as useful diagnostic indexes for cirrhotic cardiomyopathy.

[Construction of a phage antibody library and screening of anti-epidermal growth factor receptor variant III single chain antibody].

OBJECTIVE: To obtain specific anti-epidermal growth factor receptor variant III (EGFRvIII) single chain antibody (ScFv) by phage antibody library display system. METHODS: The total RNA was extracted from the spleen B cells of BALB/c mice immunized with pep-3-OVA protein, and the first-strand cDNA was synthesized by reverse transcription. Antibody VH and VL gene fragments were amplified and joined to a ScFv gene with the linker. The ScFv gene was ligated into the phagemid vector pCANTAB5E, which was transformed into competent E. coli TG1. The transformed cells were then infected with M13KO7 helper phage to yield the recombinant phage to construct the phage ScFv library. Pep-3-BSA protein was used to screen the phage antibody library and ELISA carried out to characterize the activity of the antibody. RESULTS: The VH and VL gene fragments of the antibody were about 350 bp and 320 bp in length as analyzed by agarose gel electrophoresis. The ScFv gene was 780 bp, consistent with the expected length. The recombinant phagemid with ScFv gene insert was rescued, and an immune phage ScFv library with the content of 5.0x10(6) was constructed. The recombinant ScFv phage had a titer of 3.0x10(4) cfu/ml, and the fourth phage harvest yielded 56 times as much as that of the first one. SDS-PAGE demonstrated a molecular mass of the soluble ScFv of about 28 kD. ELISA results indicated good specificity of the ScFv to bind EGFRvIII. CONCLUSION: An immune phage ScFv library is successfully constructed, and the ScFv antibody fragment is capable of specific binding to EGFRvIII.

Generation of fusion protein EGFRvIII-HBcAg and its anti-tumor effect in vivo.

The epidermal growth factor receptor variant III (EGFRvIII) is the most common variation of EGFR. Because it shows a high frequency in several different types of tumor and has not been detected in normal tissues, it is an ideal target for tumor specific therapy. In this study, we prepared EGFRvIII-HBcAg fusion protein. After immunization with fusion protein, HBcAg or PBS, the titers of antibody in BALB/c mice immunized with fusion protein reached 2.75 x 10(5). Western blot analysis demonstrated that the fusion protein had specific antigenicity against anti-EGFRvIII antibody. Further observation showed fusion protein induced a high frequency of IFN-gamma-secreting lymphocytes. CD4+T cells rather than CD8+T cells were associated with the production of IFN-gamma. Using Renca-vIII(+) cell as specific stimulator, we observed remarkable cytotoxic activity in splenocytes from mice immunized with fusion protein. Mice were challenged with Renca-vIII(+) cells after five times immunization. In fusion protein group, three of ten mice failed to develop tumor and all survived at the end of the research. The weight of tumors in fusion protein were obviously lighter than that in other two groups (t = 4.73, P = 0.044; t = 6.89, P = 0.040). These findings demonstrated that EGFRvIII-HBcAg fusion protein triggered protective responses against tumor expressing EGFRvIII.