Blood pressure lowering effects of ß-blockers as add-on or combination therapy: A meta-analysis of randomized controlled trials.

The authors performed a meta-analysis to assess the efficacy of non-atenolol ß-blockers as add-on to monotherapy or as a component of combination antihypertensive therapy in patients with hypertension. The authors searched and identified relevant randomized controlled trials from PubMed until November 2021. Studies comparing blood pressure lowering effects of ß-blockers with diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) were included. The analysis included 20 studies with 5544 participants. ß-blockers add-on to monotherapy significantly reduced systolic and diastolic blood pressure as compared with non-ß-blocker monotherapy (weighted mean difference in mm Hg [95% confidence interval]: -4.1 [-6.0, -2.2] and -3.7 [-4.6, -2.8], respectively). These results were consistent across the comparisons with diuretics (systolic pressure, -10.2 [-14.2, -6.2]; diastolic pressure, -5.4 [-8.2, -2.6]), CCBs (systolic pressure, -4.1 [-7.1, -1.0]; diastolic pressure, -2.8 [-4.1, -1.5]), and ACEIs/ARBs (systolic pressure, -2.9 [-4.3, -1.5]; diastolic pressure, -4.2 [-5.0, -3.4]). There was no significant difference in blood pressure lowering effects between combinations with and without a ß-blocker (systolic pressure, -1.3 mm Hg [-5.8, 3.2]; diastolic pressure, -.3 mm Hg [-2.7, 2.1]). Metoprolol add-on or combination therapy had a significantly greater blood pressure reduction than non-ß-blocker therapy (systolic pressure, -3.6 mm Hg [-5.9, -1.3]; diastolic pressure, -2.1 mm Hg [-3.5, -.7]). In conclusion, non-atenolol ß-blockers are effective in lowering blood pressure as add-on to monotherapy or as a component of combination antihypertensive therapy. In line with the current hypertension guideline recommendations, ß-blockers can and should be used in combination with other antihypertensive drugs.

[Effect of cordycepin on CX43 expression in the corpus cavernosum of type II diabetes induced erectile dysfunction in rats].

OBJECTIVE: To study the effect of cordycepin on the expression of connexin 43 (CX43) in the corpus cavernosum tissue of the ED rats with type II diabetic mellitus (DM). METHODS: Forty male SD rats were fed with high-fat diet and injected intraperitoneally with STZ solution to induce type II DM, and then divided into 4 groups of an equal number: DM model control, low-dose cordycepin (10.0 mg/kg/d), high-dose cordycepin (30.0 mg/kg/d) and sildenafil positive control (5.0 mg/kg/d). Another 10 male SD rats were taken as blank controls and fed with normal diet. After 6 weeks of intervention, the sexual behavior of the rats was observed, the ratio of intra-cavernous pressure to mean arterial pressure (ICP/MAP) measured, and the corpus cavernosal tissue harvested for observation of the morphology and determination of the expression level of CX43 in the corpus cavernosum by immunohistochemistry. RESULTS: Compared with the DM model controls, the rats in the high-dose cordycepin group showed significantly improved latency and frequency of captures (P < 0.01), increased ICP/MAP ratio (P < 0.05), and improved morphology of the corpus cavernosal tissue. The expression of CX43 was found mainly in the smooth muscle cells of the penile corpus cavernosum, and dramatically higher in the high-dose cordycepin group than in the DM model controls (P < 0.01). CONCLUSION: Cordycepin can effectively improve the erectile function of type Ⅱ diabetic rats by up-regulating the expression of CX43 in the penile corpus cavernosum.

Is the newest angiotensin-receptor blocker azilsartan medoxomil more efficacious in lowering blood pressure than the older ones? A systematic review and network meta-analysis.

Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more effective than the older ones. A network meta-analysis was performed to compare the efficacy of various angiotensin-receptor blockers in reducing office and ambulatory blood pressure in hypertensive patients. Relevant literature was searched from English and Chinese databases for randomized controlled trials involving angiotensin-receptor blockers in hypertension. Efficacy variables included systolic and diastolic blood pressure either in the office or on ambulatory blood pressure monitoring. Absolute blood pressure reductions at 6-12 weeks of treatment and their credible intervals were reported. A total of 34 publications provided adequate data for analysis (n = 14 859). In 28 studies on office systolic blood pressure (n = 12 731), against the common comparator valsartan 80 mg, the differences in systolic blood pressure were in favor of azilsartan medoxomil (20-80 mg), irbesartan (300 mg), olmesartan (20-40 mg), telmisartan (80 mg), and valsartan (160-320 mg), but not candesartan (8-16 mg), losartan (50-100 mg), irbesartan (150 mg), olmesartan (10 mg), and telmisartan (40 mg). The ranking plot shows that azilsartan medoxomil 80 mg had a possibility of 99% being the best in the class. Similar results were observed for office diastolic blood pressure and from 13 studies for 24-hour ambulatory systolic and diastolic blood pressure. In conclusion, angiotensin-receptor blockers had different blood pressure lowering efficacy. The newest angiotensin-receptor blocker azilsartan medoxomil at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement.

TWIST1 induces phenotypic switching of vascular smooth muscle cells by downregulating p68 and microRNA-143/145.

TWIST1 is an important basic helix-loop-helix protein linked to multiple physiological and pathological processes. Although TWIST1 is believed to be involved in vascular pathogenesis, its effects on homeostasis of smooth muscle cells (SMCs) remain poorly understood. Here, we show that TWIST1 protein levels were significantly elevated during SMC phenotypic switching in vivo and in vitro. TWIST1 overexpression promoted phenotypic switching of SMCs, while siRNA targeting of TWIST1 prevented cell transition. Mechanistically, TWIST1 decreased the level of microRNA-143/145, which governs smooth muscle marker gene transcription. In addition, TWIST1 repressed p68 mRNA and protein expression, a crucial modulator of SMC behavior and microRNA biogenesis. Our co-immunoprecipitation assay demonstrated a previously unrecognized molecular interaction between TWIST1 and p68 protein. Finally, we found that TWIST1 triggered SMC phenotypic switching and suppressed microRNA-143/145 expression by promoting the proteasomal degradation of p68. These data suggest a novel role of TWIST1 in the regulation of SMC homeostasis by modulating p68/microRNA-143/145 axis.

Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer's disease-type pathology and cognitive deficits in APP/PS1 mice.

Alzheimer's disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aß) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aß burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aß generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.

2019 Chinese Hypertension League guidelines on home blood pressure monitoring.

In China, automated blood pressure monitors have been readily available for home use. Home blood pressure monitoring has been indispensable in the management of hypertension. There is therefore a need to establish guidelines for home blood pressure monitoring on the basis of the 2012 consensus document. In this guidelines document, the committee put forward recommendations on the selection and calibration of blood pressure measuring devices, the frequency (times) and duration (days) of blood pressure measurement, and the diagnostic threshold of home blood pressure.

A randomized controlled trial on the blood pressure-lowering effect of amlodipine and nifedipine-GITS in sustained hypertension.

In a multicenter, randomized trial, we investigated whether the long half-time dihydropyridine calcium channel blocker amlodipine was more efficacious than the gastrointestinal therapeutic system (GITS) formulation of nifedipine in lowering ambulatory blood pressure (BP) in sustained hypertension (clinic systolic/diastolic BP 140-179/90-109 mm Hg and 24-hour systolic/diastolic BP ≥ 130/80 mm Hg). Eligible patients were randomly assigned to amlodipine 5-10 mg/day or nifedipine-GITS 30-60 mg/day. Ambulatory BP monitoring was performed for 24 hours at baseline and 4-week treatment and for 48 hours at 8-week treatment with a dose of medication missed on the second day. After 8-week treatment, BP was similarly reduced in the amlodipine (n = 257) and nifedipine-GITS groups (n = 248) for both clinic and ambulatory (24-hour systolic/diastolic BP 10.3/6.5 vs 10.9/6.3 mm Hg, P ≥ 0.24) measurements. However, after missing a dose of medication, ambulatory BP reductions were greater in the amlodipine than nifedipine-GITS group, with a significant (P ≤ 0.04) between-group difference in 24-hour (-1.2 mm Hg) and daytime diastolic BP (-1.5 mm Hg). In conclusion, amlodipine and nifedipine-GITS were efficacious in reducing 24-hour BP. When a dose of medication was missed, amlodipine became more efficacious than nifedipine-GITS.

Differential protein profiles in duck meat during the early postmortem storage period.

The present study was designed to investigate proteomic differences in duck breast muscle during the early postmortem storage period. The meat quality was evaluated at 0 hr and 24 hr postmortem at 4°C in Pekin ducks, black Muscovy ducks and Mule ducks. Differentially expressed proteins were detected by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF/TOF MS) at 0 hr and 24 hr postmortem in the three duck breeds. The results showed that 53 proteins spots were differentially expressed at 0 hr and 24 hr postmortem at 4°C in Pekin ducks, 75 spots in black Muscovy ducks, and 72 spots in Mule ducks. A total of 30 (10 spots for each breed) were selected for identification by mass spectrometry. Seven proteins were identified in Pekin ducks, eight in black Muscovy ducks and seven in Mule ducks. Moreover, the above results obtained by 2-DE and MALDI-TOF/TOF MS were confirmed by western blotting. To our knowledge, this study is the first to provide insights into the protein profiles of ducks during postmortem storage and provides a better understanding of the biochemical processes that contribute to duck meat quality.

Activation of Endogenous Cardiac Stem Cells by Apelin-13 in Infarcted Rat Heart.

Our previous study demonstrated that the apelin-APJ pathway contributed to myocardial regeneration and functional recovery after bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation during the differentiation of BM-MSCs into cardiomyogenic cells in acute myocardial infarction (AMI) rat models. However, the underlying mechanisms by which apelin promotes cardiac repair and functional recovery have not been completely clarified. In the present study, we investigated whether apelin could mobilize and activate endogenous cardiac stem cells and progenitors, thereby mediating regeneration and repair of the myocardium after AMI in rat models. Six-week-old male Sprague-Dawley rats underwent AMI and received apelin-13 (200 ng, n = 10) or an equivalent volume of saline by intramyocardial injection (n = 10); there was also a sham operation group (n = 8). Proliferation of endogenous cardiac stem cells was analyzed by immunofluorescence staining in rat infarcted myocardium, and heart function was evaluated by echocardiography at 28 days after apelin-13 injection. Treatment with apelin-13 led to a significant increase of Ki-67+-c-kit+/Sca-1+/Flk-1+ endogenous cardiac stem or progenitor cells in the border zone and infarct zone of rat hearts at 28 days after myocardial infarction (MI). Significant increases in the expression of c-kit, Sca-1, and Flk-1 on both levels of transcription and translation were confirmed by real-time polymerase chain reaction (RT-PCR) and Western blot. Treatment of apelin-13 also resulted in a significant reduction of infarct size and improvement of cardiac function post-MI. We conclude that apelin-13 is able to enhance mobilization, survival, and proliferation of endogenous myocardial stem cells in the injured heart, providing a novel mechanistic explanation for how apelin-13 might repair the heart and improve cardiac function. Thus, apelin-13 or pharmacological agonists of the APJ receptor could act as novel therapies for heart regeneration.

Apelin: an endogenous peptide essential for cardiomyogenic differentiation of mesenchymal stem cells via activating extracellular signal-regulated kinase 1/2 and 5.

Growing evidence has shown that apelin/APJ system functions as a critical mediator of cardiac development as well as cardiovascular function. Here, we investigated the role of apelin in the cardiomyogenic differentiation of mesenchymal stem cells derived from Wharton's jelly of human umbilical cord in vitro. In this research, we used RNA interference methodology and gene transfection technique to regulate the expression of apelin in Wharton's jelly-derived mesenchymal stem cells and induced cells with a effective cardiac differentiation protocol including 5-azacytidine and bFGF. Four weeks after induction, induced cells assumed a stick-like morphology and myotube-like structures except apelin-silenced cells and the control group. The silencing expression of apelin in Wharton's jelly-derived mesenchymal stem cells decreased the expression of several critical cardiac progenitor transcription factors (Mesp1, Mef2c, NKX2.5) and cardiac phenotypes (cardiac α-actin, ß-MHC, cTnT, and connexin-43). Meanwhile, endogenous compensation of apelin contributed to differentiating into cells with characteristics of cardiomyocytes in vitro. Further experiment showed that exogenous apelin peptide rescued the cardiomyogenic differentiation of apelin-silenced mesenchymal stem cells in the early stage (1-4 days) of induction. Remarkably, our experiment indicated that apelin up-regulated cardiac specific genes in Wharton's jelly-derived mesenchymal stem cells via activating extracellular signal-regulated kinase (ERK) 1/2 and 5.

Diabetes mellitus is associated with early chronic venous disorder of the lower extremities in Chinese patients with cardiometabolic risk factors.

BACKGROUND: Metabolic syndrome has received great attention because it poses a potential cardiovascular hazard, which increases the risk of lower extremity atherosclerosis. However, the relationship between the components of metabolic syndrome and the onset of chronic venous disorder of the lower extremities remains unexplained. METHODS: This study investigated the characteristics of cardiometabolic risk factors of early chronic venous disorder of the lower extremities in subjects with cardiometabolic risk. The characteristics of risk factors and diabetes-related complications in diabetic patients with early chronic venous disorder of the lower extremities were also investigated. In addition, the association between early chronic venous disorder and atherosclerosis of the lower extremities was analysed. The study examined 782 subjects with cardiometabolic risk factors, including obesity, hypertension, diabetes mellitus and dyslipidaemia. Lower extremity venous function was measured by digital photoplethysmography. RESULTS: Women had a higher prevalence of early chronic venous disorder than did men (p < 0.01). Male subjects with early chronic venous disorder had a higher systolic blood pressure than those with normal venous function (p < 0.01), and female subjects with early chronic venous disorder had a higher fasting plasma glucose level than did controls (p < 0.05). The prevalence of diabetes mellitus is also significantly higher in female patients with early chronic venous disorder (p = 0.000). Diabetic patients with early chronic venous disorder not only had higher fasting plasma glucose and total cholesterol levels but also had more serious macrovascular complications than the control group. The independent risk factors of early chronic venous disorder in female subjects with cardiometabolic risks were age and fasting plasma glucose in men it was only age Women face a two times greater risk than men. The independent risk factors of early chronic venous disorder in diabetic patients were age, gender, HbA1c and triglyceride levels Women had an almost 12 times greater risk of early chronic venous disorder than men. Among the diabetic patients, the prevalence of early chronic venous disorder did not differ by ankle-brachial index. CONCLUSION: Female subjects with cardiometabolic risk factors or female diabetic patients face a greater risk of early chronic venous disorder than do male subjects. Diabetic patients with early chronic venous disorder had more serious macrovascular complications than did the controls, and the early venous function was found to be correlated with the blood glucose level and triglyceride status.

Prevalence and predictors of decreased glomerular filtration rate in tibetan children with congenital heart disease.

OBJECTIVES: To assess the prevalence of decreased glomerular filtration rate (GFR) in Tibetan children with congenital heart disease (CHD) and its associated risk factors. METHODS: A total of 207 Tibetan children attending authors' center for treatment of CHD from May 2012 through November 2012, were included in the study. GFR was estimated with the Schwartz formula (eGFR). RESULTS: The mean eGFR was 104.3±16.6 mL/min/1.73 m2, and decreased in 21 children (10.1%). In the cyanotic category, eGFR was decreased only in severely cyanotic individuals. In the acyanotic category with left ventricular overload, children with decreased eGFR were younger, more commonly lived in areas above 4,700 m, and had higher left ventricular internal dimensions indexed by body surface areas (LVID/BSA) (53.8±6.9 vs. 40.1±6.8 mm/m2, P<0.001) compared with those with normal eGFR. Multivariate analysis identified LVID/BSA as the only independent predictor for decreased eGFR (OR: 1.329, 95% CI: 1.177~1.501, P<0.001). Receiver operating characteristic analysis showed the area under curve for LVID/BSA was 0.921 (95% CI: 0.863 ~ 0.980, P<0.001), with the optimal cutoff value of 49.8 mm/m2 (sensitivity: 75.0%, specificity: 93.9%). In the remaining category, decreased eGFR was only observed in those living above 4,700 m. CONCLUSIONS: One tenth of Tibetan children with CHD had decreased eGFR. The risk factors included severe cyanosis, younger age, living above 4,700 m and higher LVID/BSA.

Prevalence of symptomatic congenital heart disease in Tibetan school children.

The prevalence of congenital heart disease (CHD) in Tibet has not been fully investigated. The aim of this study was to illustrate and compare the prevalence of symptomatic CHD and its major subtypes in Tibetan children at different altitudes. A total of 5,790 children from regions at altitudes of 3,500 to 4,100 m (group L) and 4,548 children from 4,200 to 4,900 m (group H) were compared for CHD prevalence. Group H had greater prevalence of total CHD (12.09 vs 4.32 per 1,000, p <0.001), patent ductus arteriosus (PDA, 7.70 vs 1.38 per 1,000, p <0.001), and atrial septal defect (ASD, 3.52 vs 2.25 per 1,000, p = 0.23) than group L. The differences were more remarkable in women (CHD, 18.63 vs 4.88 per 1,000, p <0.001; PDA, 11.53 vs 1.74 per 1,000, p <0.001; ASD, 5.32 vs 2.79 per 1,000, p = 0.15). No significant difference was observed in the prevalence of ventricular septal defect between the 2 groups (0.44 vs 0.35 per 1,000, p >0.05). The most common cardiac defect was ASD (52.0%) in group L compared with PDA (63.6%) in group H. In group L, women had slightly and insignificantly greater prevalence of total CHD, PDA, and ASD than men. In contrast, the prevalence was almost threefold greater in women than men in group H. In conclusion, the CHD prevalence and composition differed significantly between populations of school children living above and below 4,200 m.

[Status of glucose metabolism in Chinese essential hypertensive patients].

OBJECTIVE: To investigate glucose metabolism status and its relationship with blood pressure, obesity, renal function and cardio-cerebral vascular events in Chinese essential hypertensive patients. METHODS: Essential hypertensive patients without diabetic history were enrolled in this cross-sectional survey. All patients filled in questionnaires and received physical examination and laboratory tests. Oral glucose tolerance test (OGTT, fasting and 2 hours glucose level after drinking the 75 g glucose solution) was performed in patients who signed the informed consent. RESULTS: (1) The control rate of systolic BP was lower in patients with dysglycemia than in patients without dysglycemia (41.0% vs. 46.4%, P = 0.000). (2) The albuminuria detection rate and the abnormal rate of estimated glumerular filtration rate (eGFR) increased significantly with the deterioration of glucose metabolism. (3) Multifactor-analysis showed that abnormal waist circumference, decreased eGFR and presence of albuminuria were independent risk factors for abnormal glucose metabolism. Cardiovascular events was significantly higher in patients with abnormal glucose metabolism than patients with normal glucose metabolism. CONCLUSION: Abnormal glucose metabolism is common in Chinese essential hypertensive patients. When complicated with abnormal glucose metabolism, essential hypertensive patients had poor blood pressure control rate and were related to higher cardiovascular risk.

[Characteristics and related risk factors of arterial elasticity in prehypertensive persons].

OBJECTIVE: To explore the characteristics and related risk factors of arterial elasticity in persons with prehypertension, high-normal blood lipid and(or) impaired glucose regulation(impaired fasting glucose and(or) impaired glucose tolerance). METHODS: After receiving physical and biochemical examinations, a total of 1238 persons were enrolled. Among them, the etiologies were prehypertension (n = 65), high-normal blood lipid (n = 156), impaired glucose regulation (n = 159), prehypertension and high-normal blood lipid (n = 85), prehypertension and impaired glucose regulation (n = 77), high-normal blood lipid and impaired glucose regulation (n = 55) and prehypertension, high-normal blood lipid and impaired glucose regulation (n = 9). Also 332 healthy subjects, 113 hypertensive patients, 150 hyperlipidemics and 37 diabetics were enrolled as controls. Systemic vascular compliance (SVC), systemic vascular resistance (SVR), brachial artery distensibility (BAD) were measured with Dynapulse 200 M (Pulse Metric, Inc., USA). RESULTS: In persons with prehypertension, SVC was lower than healty group ((1.14 ± 0.20) ml vs (1.26 ± 0.23) ml, P < 0.01)and higher than hypertensive group ((1.11 ± 0.18) ml, P = 0.011), SVR higher than healty group (157 ± 29) kPa×s×L(-1) vs (148 ± 25) kPa×s×L(-1), P = 0.012) and lower than hypertensive group ((166 ± 36) kPa×s×L(-1), P < 0.01)and BAD lower than healty group(5.93% ± 1.14% vs 6.50% ± 1.30%, P < 0.01). Among different groups with prehypertension, high-normal blood lipid and(or) impaired glucose regulation, SVC, SVR and BAD had significant differences. As indicated by multiple linear regression analysis, blood pressure was an independent risk factor of arterial elasticity. CONCLUSIONS: Vascular function becomes damaged in prehypertensive stage. As an independent risk factor, blood pressure had more potent effect than lipid and blood glucose. Multiple cardiovascular risk factors with high-normal value may affect vascular function more strongly.

Common expression of stemness molecular markers and early cardiac transcription factors in human Wharton's jelly-derived mesenchymal stem cells and embryonic stem cells.

At present, there are still significant barriers that impede the clinical use of hESCs and iPS cells, including ethics, immunorejection, tumorigenesis from hESCs, and teratoma formation from iPS cells. It is therefore necessary to search for alternative sources of stem cells. WJ-MSCs originate from embryonic epiblasts and possess properties intermediate between hESCs and adult stem cells. However, the stemness properties of molecules in WJ-MSCs remain unclear compared to those of hESCs. In the present study, we isolated WJ-MSCs by a nonenzymatic method. Further, using microarray analysis by Affymetrix GeneChip and functional network analyses, we determined the degree of expression of stemness genes exhibited by the Human Stem Cell Pluripotency array. We also defined a wide range of stem cell gene expression in the WJ-MSCs in comparison with hESCs. At the same time, the definitive markers of early cardiac precursor cells and more committed progenitors were further characterized in WJ-MSCs. Our results demonstrated for the first time that WJ-MSCs had significant expression of undifferentiated human embryonic stem cell core markers, such as SOX2, NANOG, LIN28, SSEA1, SSEA3, SSEA4, KLF4, c-MYC, CRIPTO, and REX1, with a relatively lower level of expression than in hESCs. We also found WJ-MSCs have high expression of early cardiac transcription factors, such as Flk-1, Isl-1, and Nkx2.5. Functional analysis revealed signature genes of WJ-MSCs with specific roles involved in immune, cytoskeletal, and chemokine regulation, cell adhesion, and cell signaling. Our study indicated that there is a significant overlap between the stemness genes expressed by hESCs and WJ-MSCs. WJ-MSCs harbor a true stem cell population and are promising cells for stem cell-based therapies.

[Correlation between computed tomographic vascular convergence sign and enhancement value in patients with pulmonary nodules].

OBJECTIVE: To explore the correlation between computed tomographic (CT) vascular convergence sign and enhancement value in patients with pulmonary nodules. METHODS: A total of 708 consecutive patients with pulmonary nodule received dual-source CT scan from January 2010 to January 2012. They were divided into vascular convergence sign group (including 4 subgroups) and non-vascular convergence sign group. Then the correlation between CT vascular convergence sign and enhancement values was analyzed. RESULTS: The enhancement values in vascular convergence sign group were significantly higher than those in non-vascular convergence sign group ((27.6 ± 10.5) vs (3.2 ± 2.8) HU, P = 0.000). The CT enhancement values in lesions tended to increase with the number of connecting blood vessels. However, no significant differences existed among the subgroups (P > 0.05). The accuracy of vascular convergence sign for detection of pulmonary malignant nodules was 84.9%, 70.6% and 60.3% according to the standards of CT enhancement values ≥ 15, 20, 25 HU respectively. The sensibility, specificity and accuracy of determining pulmonary malignant nodules were 97.2%, 68.8% and 93.7% according to the standard of vascular convergence sign. The accuracy of determining pulmonary nodules' CT enhancement values ≥ 15 HU was 88.1% according to the standard of vascular convergence sign. CONCLUSION: Vascular convergence sign may be used to indicate the enhancement of pulmonary nodules when CT enhancement images are not available.

[Activation of transient receptor potential vanilloid 1 inhibits RhoA/Rho kinase and improves vasorelaxation dysfunction mediated by high-fat diet in mice].

OBJECTIVE: To investigate the role of dietary capsaicin in activating transient receptor potential vanilloid 1 (TRPV1) and thus influencing the vascular dysfunction mediated by high-fat diet and the potential mechanisms. METHODS: A total of 80 male C57BL/6J mice aged 10 weeks were equally divided into four groups, in which the mice were fed with normal diet (ND), normal diet plus capsaicin (NC), high-fat diet (HD), or high-fat diet plus capsaicin (HC) for 20 weeks. Tail-cuff blood pressure (BP), vascular function of mice aortic rings, expressions of voltage-gated potassium-channel Kv1.4, RhoA and Rho kinase in aorta were examined. RESULTS: Compared with ND group, both nitroglycerin [(18.9 +/- 13)% vs. 100%, P < 0.01] and acetylcholine [(26 +/- 12)% vs. 100%, P < 0.01] induced vasorelaxation of aortic rings were significantly reduced in HD group. Both endothelium dependent and independent aortic rings vasorelaxation in HC group were significantly improved compared with that in HD group [acetylcholine: (69 +/- 15)%; nitroglycerin: (46.5 +/- 6)%, P < 0.05], but still reduced compared with that in ND group (P < 0.05, P < 0.01). High fat diet induced the expression of RhoA and Rho kinase. Dietary capsaicin down-regulated the expression of RhoA and Rho kinase but up-regulated the expression of Kv1.4 in aorta in mice fed with normal or high fat diet (all P < 0.05). CONCLUSION: Dietary capsaicin can ameliorate vasorelaxation dysfunction mediated by high-fat diet. The potential mechanisms may be related with TRPV1 activation, which in turn stimulates potassium channel and inhibits RhoA and Rho kinase in the vasculature.

The apelin-APJ pathway exists in cardiomyogenic cells derived from mesenchymal stem cells in vitro and in vivo.

Our previous study demonstrated that apelin level increased significantly after the treatment of intracoronary implantation of bone marrow mononuclear cells (BMMCs), followed by the improvement of cardiac function in patients with severe ischemic heart failure. The present studies both in vivo and in vitro explored whether mesenchymal stem cells derived from bone marrow (BMSCs) activate the apelin-APJ pathway when differentiating into cardiomyogenic cells. Isolated BMSCs from rat femurs and tibias were cultured and expanded for three passages, labeled with DAPI, and treated with 5-azacytidine (5-AZ). BMSCs labeled with ad-EGFP were injected intramyocardially into the peri-infarct area of rat models with acute myocardial infarction. Immunofluorescence staining exposed that CMGs expressed apelin together with myogenic-specific proteins such as α-actin, troponin T, GATA-4, and connexin-43 at 7 days after 5-AZ treatment or EGFP-BMSC injection. RT-PCR revealed that mRNA in CMGs started to express apelin and APJ from day 7 and progressively increased until day 28. Cardiac function, as measured by echocardiography in vivo, was significantly improved in parallel with the extent of apelin expression after BMSC transplantation. Our finding indicated that the expression of the apelin-APJ pathway during differentiation of BMSCs into CMGs may be an important mechanism in regulation of myocardial regeneration and functional recovery after BMSC transplantation.