[Effect of RDN on long-term blood pressure in refractory hypertensive patients with different cardiovascular risk stratification].

Objective: To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality. Methods: This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone. Results: A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa),P=0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg,P=0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg,P=0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P>0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P>0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P>0.05). Conclusions: RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.

Effect of miR-203 expression on myocardial fibrosis.

OBJECTIVE: Cardiovascular disease is one of the diseases threatening human health. Myocardial fibrosis is a major cause of cardiovascular diseases. Studies have shown that over expression of miR-203 can inhibit the fibrosis. Therefore, in this study, the effect of differential expression of miR-203 on fibrosis of cultured mouse cardiomyocytes was investigated. MATERIALS AND METHODS: Activators and inhibitors of miR-203 were designed according to the sequence of miR-203, synthesized, and transfected into mouse cardiomyocytes to establish activator group, inhibitor group, and control group. The expression levels of fibrosis-related factors including FN, CTGF, and TGF-ß1 were measured by Western blot and RT-PCR 24 h and 36 h after transfection. RESULTS: Over-expression of miR-203 in mouse cardiomyocytes significantly decreased the expression levels of TGF-ß1, CTGF, and FN in a time-dependent manner, compared with that in the control group (p <0.05). Inhibition of miR-203 expression in mouse cardiomyocytes significantly increased the expression levels of TGF-ß1, CTGF, and FN 36 h after transfection, compared with that in the control group (p < 0.05). No significant differences were seen in the expression levels of TGF-ß1, CTGF, and FN 24 h after transfection, compared with that in the control group (p >0.05). CONCLUSIONS: Over-expression of miR-203 in mouse cardiomyocytes significantly decreased the expression levels of TGF-ß1, CTGF, and FN, which might be used as a detection index for prediction of fibrosis.

Correlation of serum PCSK9 in CHD patients with the severity of coronary arterial lesions.

OBJECTIVE: The present study aims to investigate the correlation between serum level of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the severity of coronary arterial lesion in patients with coronary heart disease (CHD). PATIENTS AND METHODS: Between August 2010 and January 2015, 126 CHD patients and 70 patients with coronary arterial stenosis < 50% (controls) were included in the present study. Serum PCSK9 level was determined using ELISA. Demographic characteristics, relevant clinical data and biochemical data were collected from all patients, and their relationship with PCSK9 was analyzed to evaluate the correlation of PCSK9 expression with the severity of coronary artery disease (CAD). RESULTS: Concentrations of total cholesterol (TC) and fasting blood sugar (FBS) were significantly higher in CHD patients than in controls (p < 0.05). No significant differences were observed in gender, age, body mass index (BMI), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), family history, smoking history and history of hypertension between groups (p > 0.05). Serum PCSK9 levels in the CHD group were significantly higher than those in the control group [(96.4 ± 33.2) ng/mL vs. (81.8 ± 27.6) ng/mL, p < 0.05]. Compared with those of patients with single-vessel or double-vessel disease, PCSK9 levels were significantly elevated in patients with multi-vessel disease (p < 0.05). The Gensini score of the CHD group was significantly lower than that of the control group (11.4 ± 10.5 vs. 37.3 ± 10.3, p < 0.05). The Gensini score of patients with multi-vessel disease was significantly higher compared with patients of single-vessel  or double-vessel disease (p < 0.05). Correlation analysis revealed that PCSK9 was positively correlated with many clinical parameters, including age, BMI, TC, TG, systolic blood pressure, FBS, Gensini score and LDL-C (p < 0.05). However, PCSK9 was not correlated with either gender ratio or diastolic blood pressure (p > 0.05). CONCLUSIONS: Serum PCSK9 level is significantly elevated in CHD patients and its variation is correlated with the severity of CAD.

Epiregulin can promote proliferation of stem cells from the dental apical papilla via MEK/Erk and JNK signalling pathways.

OBJECTIVES: Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but their molecular mechanisms of differentiation and proliferation remain unclear; this situation has restricted use of MSCs to a limited number of applications. A previous study of ours found a member of the epidermal growth factor family, epiregulin (EREG), to be involved in regulation of MSC differentiation. In the present study, we have used human dental stem cells from the apical papilla (SCAPs) to investigate the role of EREG on proliferation of MSCs. MATERIALS AND METHODS: SCAPs were isolated from apical papillae of immature third molars. Retroviral short hairpin RNA (shRNA) was used to silence EREG gene expression, and human recombinant EREG protein was used to stimulate SCAPs. SCAP proliferation was examined using tetrazolium dye colorimetric assay/cell growth curve. Western blotting was performed to detect expressions of extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), mitogen-activated protein kinases 1 and 2 (MEK1/2), protein kinase B (Akt), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). RESULTS: Depletion of EREG with shRNA inhibited SCAP proliferation and repressed phosphorylation of Erk1/2 and JNK. Human recombinant EREG protein promoted cell proliferation and enhanced Erk1/2, MEK and JNK phosphorylation in SCAPs. Furthermore, blocking MEK/Erk signalling with specific Erk1/2 inhibitor PD98059, or JNK signalling with specific inhibitor SP600125, abolished effects of EREG on cell proliferation. CONCLUSION: These findings indicate that EREG could enhance cell proliferation in dental tissue-derived MSCs by activating MEK/Erk and JNK signalling pathways.

Level set based auto segmentation of the tagged left ventricle MR images.

To facilitate automatic segmentation, we adopt SVM (Support Vector Machine) to localize the left ventricle, and the segmentation is then carried out with narrow band level set. The method of generating the narrow band is improved such that the time used is reduced. Based on the imaging characteristics of the tagged left ventricle MR images, BPV (block-pixel variation) and intensity comparability are introduced to improve the speed term of level set and to increase the precision of segmentation. Our method can perform the segmentation of the tagged left ventricle MR images accurately and automatically.

Destruction of parotid glands affects nitrate and nitrite metabolism.

The role of salivary glands in nitrate and nitrite metabolism is poorly understood. The aim of the present study was to investigate the effect of parotid gland ablation on dynamic metabolism of nitrate and nitrite in miniature pigs. The parotid glands of 5 healthy miniature pigs were bilaterally ablated by methyl violet. Concentrations of nitrate and nitrite of whole saliva, serum, and urine samples were analyzed by high-performance liquid chromatography. Results showed that bilateral ablation of the parotid glands led to a significant decrease of nitrate secretion from blood to saliva (P < 0.05) and thus low nitrite levels. Dysfunction of the parotid glands temporarily increased the systemic level of nitrate in miniature pigs after nitrate loading. This study suggests that the parotid glands play an important role in the balance of nitrate and nitrite levels in both whole saliva and the body.

[Analysis of dynamic blood pressure of essential hypertension patients with Ganyang shangkangzheng or Gan-shengyinxuzheng].

Inspecting twenty-four hours dynamic blood pressure of sixty-two essential hypertension patients with Ganyang shangkangzheng or Gan-shengyinxuzheng in normal conditions and analysing blood pressure's dynamic regularity of the two groups with different traditional Chinese medicine Zheng type, we found that the blood pressure of Ganyang shangkangzheng patients was higher in the daytime than that at night, and the Gan-Shengyinxuzheng patients had the reverse results. The results suggest that the dynamic blood pressure value may be an objective index for differential diagnosis of traditional Chinese medicine Zheng types of patients with essential hypertension.