[Clinical features of patients with pulmonary artery hypertension associated with hereditary hemorrhagic telangiectasia].

OBJECTIVE: To investigate the clinical manifestations of patients with pulmonary artery hypertension (PAH) associated with hereditary hemorrhagic telangiectasia (HHT). METHODS: This retrospective analysis summarized the clinical features of 6 patients with PAH associated with HHT hospitalized at department of cardiology in Cardiovascular Institute and Fuwai Hospital between January 2006 and May 2009. RESULTS: The mean age of the 6 patients (3 male) was 34 years (8 - 67 years). Recurrent epistaxis were present in all patients, there were 4 patients with severe PAH and 2 patients with moderate PAH. All of the six patients with PAH associated with HHT were misdiagnosed at the first hospital visit. Clinical symptoms were significantly improved in 4 patients and remained unchanged in 2 patients combined hepatic venous malformation post medical therapy. CONCLUSIONS: Misdiagnosis for patients with PAH associated with HHT is a common phenomenon in daily clinical practice. Patients could benefit from the corresponding medical therapy after the establishment of the correct diagnosis.

Modulating Three-Dimensional Microenvironment with Hyaluronan of Different Molecular Weights Alters Breast Cancer Cell Invasion Behavior.

Hyaluronan (HA), a polymer with various molecular weights (MW) found in tumor microenvironments, is associated with malignant progression of breast cancer. Reducing the amount of high-MW HA in the microenvironment by hyaluronidase is a promising approach for breast cancer treatment. However, whether the generation of HA fragments negatively affects breast cancer cells remains to be determined. Furthermore, HA forms three-dimensional (3D) networks by cross-linking with other extracellular molecules to function. Therefore, a model mimicking the cross-linked HA network is required to determine the effect of HA fragments on breast cancer cells. To clarify the differential roles of low (HA35) versus high (HA117) MW HA on cancer cell phenotype, a 3D culture system was set up by covalently cross-linking HA with alginate and investigating the behavior of 4T-1 and SKBR3 breast cancer cells alongside a two-dimensional (2D) control. The results show the invasion and migration abilities of 4T-1 and SKBR3 cells are significantly enhanced by the presence of HA35 but inhibited by HA117 in both 2D monolayers and 3D spheroids. The differential effects of HA35 and HA117 on cancer cell epithelial-mesenchymal transition (EMT) phenotype were further confirmed in terms of differential regulation of E-cadherin and vimentin as important EMT markers at both the cellular and mRNA levels. Additional experiments show the CD44-Twist signaling pathway might be involved in the differential effects of HA35 and HA117. These results have important implications with respect to understanding the role of HA in breast cancer development and for the design of therapeutic approaches based on the eradication of HA with hyaluronidase.

An alginate-based platform for cancer stem cell research.

UNLABELLED: As the primary determinants of the clinical behaviors of human cancers, the discovery of cancer stem cells (CSCs) represents an ideal target for novel anti-cancer therapies (Kievit et al., 2014). Notably, CSCs are difficult to propagate in vitro, which severely restricts the study of CSC biology and the development of therapeutic agents. Emerging evidence indicates that CSCs rely on a niche that controls their differentiation and proliferation, as is the case with normal stem cells (NSCs). Replicating the in vivo CSC microenvironment in vitro using three-dimensional (3D) porous scaffolds can provide means to effectively generate CSCs, thus enabling the discovery of CSC biology. This paper presents our study on a novel alginate-based platform for mimicking the CSC niche to promote CSC proliferation and enrichment. In this study, we used a versatile mouse 4T1 breast cancer model to independently evaluate the matrix parameters of a CSC niche - including the material's mechanical properties, cytokine immobilization, and the composition of the extracellular matrix's (ECM's) molecular impact - on CSC proliferation and enrichment. On this basis, the optimal stiffness and concentration of hyaluronic acid (HA), as well as epidermal growth factor and basic fibroblast growth factor immobilization, were identified to establish the platform for mimicking the 4T1 breast CSCs (4T1 CSCs) niche. The 4T1 CSCs obtained from the platform show increased expression of the genes involved in breast CSC and NSC, as compared to general 2D or 3D culture, and 4T1 CSCs were also demonstrated to have the ability to quickly form a subcutaneous tumor in homologous Balb/c mice in vivo. In addition, the platform can be adjusted according to different parameters for CSC screening. Our results indicate that our platform offers a simple and efficient means to isolate and enrich CSCs in vitro, which can help researchers better understand CSC biology and thus develop more effective therapeutic agents to treat cancer. STATEMENT OF SIGNIFICANCE: As the primary determinants of the clinical behaviors of human cancers, the discovery of cancer stem cells (CSCs) represents an ideal target for novel anti-cancer therapies. However, CSCs are difficult to propagate in vitro, which severely restricts the study of CSC biology and the development of therapeutic agents. Emerging evidence indicates that CSCs rely on a niche that controls their differentiation and proliferation, as is the case with normal stem cells (NSCs). Replicating the in vivo CSC microenvironment in vitro using three-dimensional (3D) porous scaffolds can provide means to effectively generate CSCs, thus enabling the discovery of CSC biology. In our study, a novel alginate-based platform were developed for mimicking the CSC niche to promote CSC proliferation and enrichment.

[Relation between uric acid and coronary artery calcification:a community-based cross-sectional survey among Beijing natural population].

OBJECTIVE: To investigate the influence of uric acid on coronary artery calcification in the natural population in Beijing. METHODS: From April to July 2012, 903 subjects from the natural population(aged 37-76 years for men, aged 42-76 years for women)in Xishan community, Beijing, were selected to accept a survey on the risk factors of cardiovascular. Blood tests and CT coronary artery calcium scans were carried out. RESULTS: At the 1 Quartile(1 Q), 2 to 3 Quartile(2-3 Q)and 4 Quartile(4 Q)of uric acid levels, the prevalence rates of coronary artery calcium were 37.2% , 45.5% , 60.6% (P<0.001) and the coronary artery calcium scores were (109.7±333.1)AU, (133.9±356.9)AU, (200.8±459.4) AU (P < 0.001)respectively. Data from the univariate logistic regression analysis showed that with the increase of uric acid, the prevalence rates of coronary artery calcium also increased(OR2-3Q = 1.41, 95% CI:1.02-1.95, P = 0.040; OR4Q = 2.60, 95% CI:1.78-3.80, P < 0.001). However, the relationship between uric acid and coronary artery calcium disappeared when using the multivariate logistic regression analysis(OR2-3Q = 0.92, 95% CI: 0.60-1.43, P = 0.713;OR4Q = 1.38, 95% CI:0.80-2.39, P = 0.247). CONCLUSION: Uric acid did not seem to be an independent risk factor for coronary artery calcium, although the prevalence and extent of coronary artery calcium increased along with the increasing trend of uric acid.

Metabolic syndrome and coronary artery calcification: a community-based natural population study.

BACKGROUND: Little is known about the influence of metabolic syndrome (MetS) on coronary artery calcification (CAC) in China. In this article, we aimed to explore the distribution of CAC in populations with and without MetS, and estimate the influence of MetS and its components on CAC in a community-based population of Beijing. METHODS: A total of 1647 local residents of Beijing, age 40-77 years, were recruited for a cardiovascular risk factors survey and were determined fasting plasma glucose (FPG), blood lipids, and 64 multi-detector computed tomography (64-MDCT) coronary artery calcium score (CACS) measurement (Agatston scoring). The distribution of CAC was described, and the influence of MetS components on CAC was evaluated. RESULTS: In this population, the prevalence and extent of CAC increased with increasing age and both were higher in MetS subjects compared to nonMetS subjects (all P < 0.05), with the exception of those older than 65 years old. The risk of CAC increased with increasing numbers of MetS components, and the odds ratios for predicting positive CAC in subjects with 1, 2, 3, and = 4 MetS components were 1.60, 1.84, 2.12, and 3.12, respectively (all P < 0.05). Elevated blood pressure, elevated FPG, elevated triglycerides, and overweight increased the risk of CAC, yielding odds ratios of 2.64, 1.67, 1.32, and 1.37, respectively (all P < 0.05). CONCLUSIONS: In the Beijing community-based population, MetS increases the risk of CAC. The risk of CAC increases with increasing numbers of MetS components. Not only the number, but also the variety of risk factors for MetS is correlated with the risk of CAC. Elevated blood pressure, hyperglycemia, hypertriglyceridemia and overweight increase the risk of CAC.

Strategic design and recent fabrication techniques for bioengineered tissue scaffolds to improve peripheral nerve regeneration.

Bioengineered tissue scaffolds are a potential tool for improving regenerative repair of damaged peripheral nerves. Novel modes of fabrication coupled with scaffold design strategies that are based on an understanding of the biology of nerve injury offer the prospect of intervention at a more sophisticated level. We review the etiology and incidence of peripheral nerve injury and the biological events that unfold during nerve regeneration after an injury. Newly available tissue scaffold fabrication technologies using bioplotting and laser-based techniques are described. Scaffold design strategies are also discussed, including the incorporation of living cells during scaffold fabrication, inclusion of neurotrophic gradients, use of electric stimulation, inclusion of antioxidant compounds to counteract neural apotosis, and promotion of angiogenesis. Use of these advanced fabrication techniques and incorporation of one or more of these active biological strategies may eventually lead to a greater success in peripheral nerve tissue engineering.

Comparison of diagnostic accuracy and radiation dose between prospective triggering and retrospective gated coronary angiography by dual-source computed tomography.

The purpose of this study was to evaluate and compare the diagnostic accuracy and radiation dose of dual-source computed tomographic (DSCT) coronary angiography for assessment of coronary artery disease using prospective electrocardiographic triggering and retrospective electrocardiographically (ECG) gated spiral scans. One hundred sixteen patients who had undergone dual-source computed tomography and conventional coronary angiography were enrolled in this study. Fifty-four patients were scanned using retrospective ECG-gated protocols (group 1) and 62 patients using prospective ECG-triggered protocols (group 2). Diagnostic accuracy, image quality, and effective dose were compared between groups 1 and 2. Conventional coronary angiography was used as the reference standard. In total 1,709 (98.2%) coronary segments in the 116 patients were assessable with adequate image quality. Sensitivities and specificities of diagnosing coronary heart disease (≥50% stenosis) in a patient-based analysis of DSCT data were 93.3% and 88.9% in group 1 and 96.4% and 85.7% in group 2, respectively (p=0.973 and 0.761). In vessel-based analysis, sensitivities and specificities were 77.4% and 94.1% in group 1 and 79.6% and 92.3% in group 2 (p=0.983 and 0.985). Overall averaged image quality scores (using 1- to 4-point scale) in groups 1 and 2 were 3.3 ± 0.4 and 3.5 ± 0.9, respectively (p=0.268). Prevalence of good (score 3.0) and excellent (score 4.0) image qualities of coronary vessels were 95.4% in group 1 and 92.4% in group 2 (p = 0.861). Effective doses were 8.82 ± 3.50 mSv (range 3.92 to 15.36) in group 1 and 2.95 ± 1.39 mSv (range 0.99 to 6.06) in group 2 (p<0.001). In conclusion, DSCT prospective ECG-triggered coronary angiography has equivalent image quality and diagnostic value compared to that of retrospective ECG-gated scans. Radiation dose was significantly decreased using prospective electrocardiographic triggering.

What is the best contrast injection protocol for 64-row multi-detector cardiac computed tomography?

OBJECTIVE: To determine the optimal contrast injection protocol for 64-MDCT coronary angiography. MATERIALS AND METHODS: One hundred and fifty consecutive patients scheduled to undergo retrospectively electrocardiographically gated 64-MDCT. Each 30 patients were assigned to use a different contrast protocol: group 1: uniphasic protocol (contrast injection without saline flush); group 2: biphasic protocol (contrast injection with saline flush); group 3A, 3B and 3C: triphasic protocol (contrast media+different saline diluted contrast media+saline flush). Image quality scores and artifacts were compared and evaluated on both transaxial and three-dimensional coronary artery images among each contrast protocol. RESULTS: Among the triphasic protocol groups, group 3A (30%:70% contrast media-saline mixture was used in second phase) used the least contrast media and had the least frequency of streak artifacts, but there were no significant differences in coronary artery attenuation, image quality, visualization right and left heart structures. Among the uniphasic protocol group (group 1), biphasic protocol group (group 2) and triphasic protocol subgroup (group 3A), there were no significant differences in image quality scores of coronary artery (P=0.18); uniphasic protocol group had the highest frequency of streak artifacts (20 cases) (P<0.05) and had the most amount contrast media (67.0+/-5.3 ml); biphasic protocol group had the least amount of contrast media (59.9+/-4.9 ml) (P<0.05) and had the highest attenuation of left main coronary artery and right coronary artery (P<0.01), but had the least amount of clear visualization right heart structure (6 cases); triphasic protocol group (group 3A) had the most amount of clear visualization right heart structures (29 cases) were the most among the three groups (P<0.05). CONCLUSION: Biphasic protocol are superior to the traditional uniphasic protocols for using the least total contrast media, having the least Streak artifacts and without image quality degradation. However, it is also important to visualize the right atrium and ventricle, so triphasic protocol (30%:70% contrast media-saline mixture was used in second phase) should be used for 64-MDCT coronary CT angiography.