A Systematic Review on Modeling Methods and Influential Factors for Mapping Dengue-Related Risk in Urban Settings.

Dengue fever is an acute mosquito-borne disease that mostly spreads within urban or semi-urban areas in warm climate zones. The dengue-related risk map is one of the most practical tools for executing effective control policies, breaking the transmission chain, and preventing disease outbreaks. Mapping risk at a small scale, such as at an urban level, can demonstrate the spatial heterogeneities in complicated built environments. This review aims to summarize state-of-the-art modeling methods and influential factors in mapping dengue fever risk in urban settings. Data were manually extracted from five major academic search databases following a set of querying and selection criteria, and a total of 28 studies were analyzed. Twenty of the selected papers investigated the spatial pattern of dengue risk by epidemic data, whereas the remaining eight papers developed an entomological risk map as a proxy for potential dengue burden in cities or agglomerated urban regions. The key findings included: (1) Big data sources and emerging data-mining techniques are innovatively employed for detecting hot spots of dengue-related burden in the urban context; (2) Bayesian approaches and machine learning algorithms have become more popular as spatial modeling tools for predicting the distribution of dengue incidence and mosquito presence; (3) Climatic and built environmental variables are the most common factors in making predictions, though the effects of these factors vary with the mosquito species; (4) Socio-economic data may be a better representation of the huge heterogeneity of risk or vulnerability spatial distribution on an urban scale. In conclusion, for spatially assessing dengue-related risk in an urban context, data availability and the purpose for mapping determine the analytical approaches and modeling methods used. To enhance the reliabilities of predictive models, sufficient data about dengue serotyping, socio-economic status, and spatial connectivity may be more important for mapping dengue-related risk in urban settings for future studies.

Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88-Dependent Inflammation.

Diabetes manifests as chronic inflammation and leads to the development diabetic cardiomyopathy (DCM). Targeting key proteins in inflammatory signaling may provide new therapy for DCM. In this study, the authors explore the pharmacological effects and mechanisms of Schisandrin B (Sch B), a natural compound with anti-inflammatory activity against DCM. It is shown that Sch B prevents high-level glucose (HG)-induced hypertrophic and fibrotic responses in cultured cardiomyocytes. RNA sequencing and inflammatory qPCR microarray show that Sch B mainly affects myeloid differentiation primary response 88 (MyD88)-dependent inflammatory gene expression in HG-challenged cardiomyocytes. Further studies indicate that Sch B directly binds to and inhibits MyD88 activation, but does not alter MyD88-independent Toll-like receptor signaling in vivo and in vitro. Inhibiting or silencing MyD88 is associated with reduced levels of HG-induced inflammatory cytokines and myocardial injuries in vitro. Treatment of type 1 and type 2 diabetic mice with Sch B protects heart function, reduces myocardial injuries, and decreases secretion of inflammatory cytokines. Cardiomyocyte-specific MyD88 knockout also protects mice against cardiac inflammation and injury in type 1 diabetic mice. In conclusion, these studies show that cardiomyocyte MyD88 plays an apathogenetic role in DCM and Sch B specifically targets MyD88 to reduce inflammatory DCM.

Hirsutella sinensis fungus improves cardiac function in mouse model of heart failure.

Cordyceps sinensis, including Hirsutella sinensis, is a highly valuable traditional Chinese medicine and is used to treat patients with pulmonary heart disease in clinical practice. However, the underlying mechanisms of its effects remain unclear. In this study, a mouse model of heart failure established by non-thoracic, transverse aortic constriction (TAC) was developed to determine the underlying mechanisms of therapeutic effects of Hirsutella sinensis fungus (HSF) powder. The results showed that HSF treatment remarkably ameliorated myocardial hypertrophy, collagen fiber hyperplasia, and cardiac function in mice with heart failure. Using transcriptional and epigenetic analyses, we found that the mechanism of HSF mainly involved a variety of signaling pathways related to myocardial fibrosis and determined that HSF could reduce the levels of TGF-ß1 proteins in heart tissue, as well as type I and III collagen levels. These data suggest that HSF alleviates heart failure, inhibits irreversible ventricular remodeling, and improves cardiac function through the regulation of myocardial fibrosis-related signaling pathways, which can provide novel opportunities to improve heart failure therapy.

Impacts from Economic Development and Environmental Factors on Life Expectancy: A Comparative Study Based on Data from Both Developed and Developing Countries from 2004 to 2016.

Both economic development level and environmental factors have significant impacts on life expectancy at birth (LE). This paper takes LE as the research object and selects nine economic and environmental indicators with various impacts on LE. Based on a dataset of economic and environmental indicators of 20 countries from 2004 to 2016, our research uses the Pearson Correlation Coefficient to evaluate the correlation coefficients between the indicators, and we use multiple regression models to measure the impact of each indicator on LE. Based on the results from models and calculations, this study conducts a comparative analysis of the influencing mechanisms of different indicators on LE in both developed and developing countries, with conclusions as follow: (1) GDP per capita and the percentage of forest area to land area have a positive impact on LE in developed countries; however, they have a negative impact on LE in developing countries. Total public expenditure on education as a percentage of GDP and fertilizer consumption have a negative impact on LE in developed countries; however, they have a positive impact on LE in developing countries. Gini coefficient and average annual exposure to PM2.5 have no significant effect on LE in developed countries; however, they have a negative impact on LE in developing countries. Current healthcare expenditures per capita have a negative impact on LE in developed countries, and there is no significant impact on LE in developing countries. (2) The urbanization rate has a significant positive impact on LE in both developed countries and developing countries. Carbon dioxide emissions have a negative impact on LE in both developed and developing countries. (3) In developed countries, GDP per capita has the greatest positive impact on LE, while fertilizer consumption has the greatest negative impact on LE. In developing countries, the urbanization rate has the greatest positive impact on LE, while the Gini coefficient has the greatest negative impact on LE. To improve and prolong LE, it is suggested that countries should prioritize increasing GDP per capita and urbanization level. At the same time, countries should also work on reducing the Gini coefficient and formulating appropriate healthcare and education policies. On the other hand, countries should balance between economic development and environmental protection, putting the emphasis more on environmental protection, reducing environmental pollution, and improving the environment's ability of self-purification.

Partial attribute attendance in environmental choice experiments: A comparative case study between Guangzhou (China) and Brussels (Belgium).

Attribute non-attendance (ANA) in discrete choice experiment (DCE) exercises has attracted increasing, yet limited, scholarly attention. This paper attempts to investigate ANA in a comparative case study, with a focus on its patterns and their association with socioeconomic, behavioral and perceptual factors, as well as its impacts on willingness-to-pay (WTP) estimates. We deploy a four-level polytomous scale (always, often, seldom, and never considered) for respondents to state their various degrees of attribute attendance (SANA) in an identical DCE questionnaire about urban river restoration initiatives in two global cities with contrast socioeconomic contexts, yet similar request for restoring polluted and modified urban rivers, Guangzhou (south China) and Brussels (Belgium). The survey results reveal the existence of large proportions of partial attendance in two sampled cities. We use an extended mixed logit model, which incorporates separate parameters delineating each attribute's different attendance groups, to estimate respondents' average WTP values. We find that accounting for SANA could improve the goodness-of-fit of the model and affect the magnitude of mean WTP estimates. Respondents' attribute attendance level pertaining to various attributes is mainly associated with their perceived importance of urban rivers' ecosystem services, but may not be necessarily correlated with the strength of their preference for corresponding attributes as indicated by the mean WTP estimates. Whether this discontinuity between respondents' stated ANA levels and WTP estimates within Guangzhou sample questions the ability of DCEs to generate unbiased welfare estimation and policy guidance in developing countries calls for further studies.

Analysis of Gut Microbiota in Patients with Coronary Artery Disease and Hypertension.

Cardiovascular and cerebrovascular diseases are characterized by high rates of morbidity and mortality. Microbiota is closely associated with cardiovascular disease. We aimed to comprehensively analyze the microbiotas of 300 healthy controls, 300 patients with high blood pressure (HBP), and 300 patients with coronary heart disease (CHD). The results indicated no significant difference in microbiota diversity among the three groups (P > 0.05). However, differences in microbiota richness among the three groups were significant (P < 0.05). Bacteroidetes and Bacteroidia were the dominant bacteria in the CHD group, Enterobacteriales and Escherichia-shigella in the HBP group, and Acidaminococcaceae and Phascolarctobacterium in the healthy control group. The prediction results of the random forest model indicated that the population with CHD displayed prominent features with high sensitivity, indicating that microbiota detection might become a novel clinical indicator to predict and monitor the risk of cardiovascular events. The prediction of microbiota function suggested differences in oxygen supply and chronic inflammation between populations with HBP/CHD and healthy populations. Although there is no difference in gut microbiota diversity among the three groups, each group has its dominant microbiota in terms of richness.

Effects on Suxiao Jiuxin Pills in the Treatment of Patients with Acute Coronary Syndrome Undergoing Early Percutaneous Coronary Intervention: A Multicenter Randomized Double-Blind Placebo-Controlled Trial.

Objectives: Acute coronary syndrome (ACS) is an acute disease with high mortality. Although early percutaneous coronary intervention (PCI) is proved to be the practical approach in treating ACS, the incidence of cardiovascular events is still far from satisfactory. The combination of Suxiao Jiuxin Pill (SJP) and Western medicine is one conventional approach in the treatment of ACS. Many elementary and clinical trials have proved the efficacy and safety in the improvement of cardiocerebral vascular conditions. The aim of this project is to evaluate the safety and efficacy of SJP on ACS with early PCI patients. Trial Design: This is a multicenter randomized, double-blind placebo-controlled trial. Trial registration: ChiCTR-TRC-13003053. Settings: Hospitals. Subjects: A total of 200 ACS with early PCI patients were randomly divided into SJP group (n = 100) and placebo group (n = 100). Interventions: The SJP group was treated with routine treatment and SJP (taking eight SJP pills orally each time, three times per day). The placebo group was treated with routine treatment along with equal amounts of SJP placebo. The course of treatment was 6 months and a follow-up visit at 12 months. Outcome Measures: Assessments of major adverse cardiovascular events (MACE), safety assessments, adverse events, left ventricular systolic function (LVEF), Seattle angina questionnaire (SAQ), troponin C (cTNI), C-reactive protein (CRP), fibrinogen (Fib), and cystatin C (cysC). Results: The SJP group had a relatively low incidence of MACE than the placebo (p < 0.05, odds ratio: 1.916, 95% confidence interval [0.999-3.674]). LVEF was significantly higher in the SJP group than the placebo group on the 360-day follow-up (p < 0.01). SJP had a significant increase score in the SAQ subscale of physical limitation, angina frequency, and treatment satisfaction (p < 0.05). There is no significant difference in the cTNI and CRP level between the two groups. The serum concentration of Fib and cysC in the SJP was significantly decreased compared with the placebo (p < 0.05). The numbers of adverse events between the two groups were not statistically different (p > 0.05). Conclusions: SJP is associated with a reduction in MACE, and an improvement of heart function and quality of life in ACS patients with early PCI, and is probably safe to use.

Environmental amenities of urban rivers and residential property values: A global meta-analysis.

Environmental amenities and disamenities of urban rivers and their capitalization in property prices have been a major subject of empirical investigation in the hedonic price method (HPM) literature for several decades. Primary studies across the globe have nonetheless adopted varying valuation scenarios and modelling approaches. And systematic variation has been shown in homeowners' marginal willingness-to-pay (WTP) for urban rivers' amenities and disamenities, ranging between -12.2% and 63.58% price premium. To identify which valuation scenarios, socio-economic variables, and modelling characteristics might affect the quantification of urban rivers' impacts on property values, we conducted a very first meta-analysis of existing evidence to extract additional information concerning the heterogeneity in WTP estimates pertaining to urban rivers' environmental amenities and disamenities. A total of 53 observations from 30 primary studies that adopted HPM to provide WTP estimates for three prominent valuation scenarios, i.e., proximity, view and water quality, were synthesized using a random effects model. Our meta-analysis results revealed several important factors in explaining the heterogeneity in empirical WTP estimates pertaining to urban rivers' environmental amenities/disamenities. First, while all three valuation scenarios could capture urban rivers' impacts on residential property values, river view was associated with the greatest premium, followed by river water quality, and river proximity the least. Second, we found that WTP estimates were significantly higher after the year of 2000, indicating the widespread and successful river restoration and rehabilitation projects in the 21st century has driven up homeowners' environmental perception and appreciation of urban rivers' amenities, especially their clear depreciation of negative environmental disamenities, to a high level. Third, our results showed that homeowners' valuation of urban rivers was not sensitive to the macro-geographical locations of their residences, suggesting a universal overall appreciation/depreciation of urban rivers across varying cultures and societies. Instead, household income level and population density should be systematically controlled if value transfer across countries is necessary. The findings of this meta-analysis could help refine urban rivers' attributes to be incorporated into HPM studies so as to adequately quantify people's sophisticated valuation of intertwined amenities and disamenities. On the practical front, our results supported two arguments from a very utilitarian point of view. First, it appears that the visual impacts might be prioritized for river restoration projects, such as through careful revegetation of riparian areas using native species. This could harbor rich diversity of ecological functions and in the meantime maximize environmental amenities that homeowners would like to pay for. And second, cost-effective river restoration in urbanized contexts should be prioritized in densely populated areas over places with relatively low population densities. This approach might maximize the number of people who can enjoy rivers for a given budget.

Different Effects of Thiazolidinediones on In-Stent Restenosis and Target Lesion Revascularization after PCI: A Meta-Analysis of Randomized Controlled Trials.

In-stent restenosis (ISR) remains the leading problem encountered after percutaneous coronary intervention (PCI). Thiazolidinediones (TZDs) has been shown to be associated with reduced ISR and target lesion revascularization (TLR); however, the results are inconsistent, especially between rosiglitazone and pioglitazone. In this study, fourteen RCTs with a total of 1350 patients were finally included through a systematical literature search of Embase, Pubmed, the Cochrane Library, and ClinicalTrials.gov from inception to January 31, 2017. The follow-up duration of the included trials ranged from 6 months to 18 months. The results demonstrated that TZDs treatment is associated with significantly reduced risk of TLR (RR:0.45, 95%CI 0.30 to 0.67 for pioglitazone, RR:0.68, 95%CI 0.46 to 1.00 for rosiglitazone). Pioglitazone is associated with significantly reduced risks of ISR (RR:0.47, 95%CI 0.27 to 0.81), major adverse cardiac events (MACE) (RR:0.44, 95%CI 0.30 to 0.64) and neointimal area (SMD: -0.585, 95%CI -0.910 to -0.261). No significant relationship was observed between rosiglitazone and ISR (RR:0.91, 95%CI 0.39 to 2.12), MACE (RR:0.73, 95%CI 0.53 to 1.00) and neointimal area (SMD: -0.164, 95%CI -1.146 to 0.818). This meta-analysis demonstrated that TZDs treatment is associated with significant reduction in ISR, TLR and MACE for patients after PCI. Pioglitazone treatment seems to have more beneficial effects than rosiglitazone and no significantly increased cardiovascular risk was detected for both agents.

Qian Five Rhinoceros Gindeng (QFRG) protects against development of immune thrombocytopenia via miR-181a inhibition of TLR-4 expression.

AIMS: Traditional Chinese medicine (TCM) has been considered to be effective auxiliary strategy for the treatment of hemocytopenia including immune thrombocytopenia. However, the molecular mechanism is still not understood. METHODS: In present study, Qian Five Rhinoceros Gindeng (QFRG) mainly containing buffalo horn, rehmannia root, radix rubia, trogopterus dung and radix salviae miltiorrhizae administrated to thrombocytopenia mice induced by injection of MWReg30. MicroRNAs (miRNAs), Toll Like Receptors (TLRs) and cytokines were assayed in monocytes separated from mice peripheral blood. The relationship between miRNAs and TLRs was investigated in Mouse leukaemic monocyte macrophage cell line RAW264.7. RESULTS: The mice with administration of QFRG had a significant increase in platelet count, and miR-181a of monocytes was markedly up-regulated in QFRG treated group. QFRG also decreased the levels of TLR4, IL-6 and TNF-α. In addition, miR-181a inhibitor reversed the effects of QFRG on platelet count, TLR4 and cytokines. Overexpression of miR-181a in lipopolysaccharide-induced showed a decrease of TLR4, IL-6 and TNF-α level. CONCLUSIONS: QFRG protects against development of immune thrombocytopenia via miR-181a inhibition of TLR-4 expression.

Emodin prevents intima thickness via Wnt4/Dvl-1/ß-catenin signaling pathway mediated by miR-126 in balloon-injured carotid artery rats.

Neointimal proliferation after vascular injury is a key mechanism of restenosis, a major cause of percutaneous transluminal angioplasty failure and artery bypass occlusion. Emodin, an anthraquinone with multiple physiological activities, has been reported to inhibit proliferation of vascular smooth muscle cells (VSMCs) that might cause intimal arterial thickening. Thus, in this study, we established a rat model of balloon-injured carotid artery and investigated the therapeutic effect of emodin and its underlying mechanism. Intimal thickness was analyzed by hematoxylin and eosin staining. Expression of Wnt4, dvl-1, ß-catenin and collagen was determined by immunohistochemistry and/or western blotting. The proliferation of VSMC was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and electron microscopy. MicroRNA levels were quantified by real-time quantitative PCR. Emodin relieved injury-induced artery intimal thickness. Results of western blots and immunohistochemistry showed that emodin suppressed expression of signaling molecules Wnt4/Dvl-1/ß-catenin as well as collagen protein in the injured artery. In addition, emodin enhanced expression of an artery injury-related microRNA, miR-126. In vitro, MTT assay showed that emodin suppressed angiotensin II (AngII)-induced proliferation of VSMCs. Emodin reversed AngII-induced activation of Wnt4/Dvl-1/ß-catenin signaling by increasing expression of miR-126 that was strongly supported by transfection of mimic or inhibitor for miR-126. Emodin prevents intimal thickening via Wnt4/Dvl-1/ß-catenin signaling pathway mediated by miR-126 in balloon-injured carotid artery of rats.

Citizens' distrust of government and their protest responses in a contingent valuation study of urban heritage trees in Guangzhou, China.

Protest response is a common aspect of contingent valuation (CV) studies, which has attracted growing attention from scholars worldwide. Distrust of government, understood as one of the major reasons for protest response, has been prevalent across transitional China experiencing dramatic changes in its economy, society and natural environment. Citizen distrust of government would significantly hinder the efficiency and validity of the contingent valuation method (CVM) application focusing on the provision of public environmental and ecological goods in China, as a large proportion of protest responses might be induced. Hitherto little has been done to link residents' trust in government to their environmental behaviors in developing and transitional economies like China where CVM has been increasingly applied to generate meaningful and reliable information for integrating both ecological and socioeconomic perspectives into policy decisions. This study aims to investigate the discrepancies between protest responses induced by distrust of government and non-protest responses, using the contingent valuation of heritage trees in Guangzhou as a case. The combination of a set of debriefing questions and several attitudinal questions is employed in the questionnaire. Based on logit analysis and discriminant analysis, it has been found that protestors who distrust government and non-protestors share similar salient values associated with urban heritage trees in Guangzhou, especially their distinctive historical and cultural values, in comparison with ordinary urban trees. Residents with low familiarity with heritage trees (who rarely visit sites with heritage trees, know little about management and conservation techniques, and consider present management to be ineffective) are likely to act as protesters with the "distrust of government" belief. Only if more opportunities are provided for residents to obtain access to urban heritage tree sites, more information (about urban heritage trees and other environmental and ecological goods) is disseminated, and more effective management is implemented, can better governmental trust be developed and stronger public participation and support secured. The results of this study can shed light on understanding protest responses in CV studies and improving the reliability and efficiency of CVM in China and other developing countries where a low level of trust in government prevails.

[Study on antibacterial property of silver loaded titanium dioxide antibacterial coated endotracheal intubation tube].

OBJECTIVE: To study the antibacterial property of silver loaded titanium dioxide (TiO2) antibacterial coated endotracheal intubation tube, and to determine the minimum effective antibacterial concentration. METHODS: Intubation tubes coated with different concentrations of antibacterial agents were prepared with sol gel method. Polyethylene endotracheal intubation tubes were used as substrate, and silver loaded TiO2 was used as the antibacterial agent. According to the different antibacterial concentrations of the antibacterial agent, the tubes were divided into nine groups: 10.0% group, 5.0% group, 2.0% group, 1.5% group, 1.0% group, 0.8% group, 0.6% group, 0.2% group, and control group. They were respectively immersed in three standard bacteria suspensions with 1.0×10(5) cfu/mL: Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. Together with standard bacteria liquid group, there were 10 experimental groups. They were kept overnight for 24 hours. 10 µL of respective culture medium was smeared on blood agar culture medium. After being cultured overnight in 35 centigrade, the number of bacteria colonies was respectively counted. RESULTS: In 1.0×10(5) cfu/mL of three standard bacteria liquids with antibacterial agent concentration ≥1.0%, three bacterial colonies had un-obviously growth rate. Almost the same strong antibacterial effects to achieve sterilizing rates of more than 98% was shown in each group of the antibacterial coating endotracheal intubation tubes (all P>0.05). As the antibacterial agent concentration decreased, three bacterial colonies were increasing gradually. Intermediate antibacterial effects were shown in tubes of 0.8% group, with significant statistic difference as compared with 1.0% and 0.6% groups [Pseudomonas aeruginosa: 7.300 (4.050, 8.350) vs. 0.200 (0.050, 1.200), 9.700(9.000, 10.000); Staphylococcus aureus: 4.100 (3.300, 4.650) vs. 0.000 (0.000, 0.150), 5.800 (5.350, 7.650); Escherichia coli: 1.400 (0.750, 3.750) vs. 0.050 (0.025, 0.050), 9.500 (8.500, 9.800), all P<0.01]. CONCLUSIONS: Silver loaded TiO2 antibacterial coated endotracheal intubation tube had definite antibacterial properties, which were related to the antibacterial concentration. Strong antibacterial effects were shown when antibacterial concentration was above 1.0%, with bacteria almost completely killed in the immersing liquid.

Wnt4/ß-catenin signaling pathway modulates balloon-injured carotid artery restenosis via disheveled-1.

BACKGROUND: Restenosis is a common adverse event of endovascular procedures and troubles cardiologists. However, the mechanism underlying restenosis is still not fully understood. To evaluate whether disheveled-1 (Dvl-1) is involved in the Wnt4/ß-catenin signaling pathway to participate in the mechanisms of vascular restenosis. METHODOLOGY: Rat model of balloon-injured carotid artery was established and atorvastatin was used to treat artery injury. Vascular smooth muscle cells (VSMC) were isolated from rats and cultured in DMEM exposed to AngII. Down-regulation and overexpression of Dvl-1 were conducted in cells to explore the role underlying its effects on VSMC proliferation and collagen expression. Adenovirus with overexpressing Dvl-1 was injected into rats to evaluate the role of Dvl-1 in artery injury rats. RESULTS: The results in vivo found that Wnt4, Dvl-1 and ß-catenin expression as well as collagen volume fraction (CVF) in injured artery were significantly increased. The results in vitro showed that Dvl-1 overexpression reversed the treatment effects of atorvastatin on VSMCs proliferation and collagen expression. It was also canceled by overexpressing Dvl-1 that the decrease of ß-catenin protein treated with atorvastatin in cells exposed to AngII. In addition, treated artery injury rats with atorvastatin, the group with injection of Ad-Dvl-1 had higher levels of intima thickness, intimal/medial area ratio and CVF. CONCLUSION: Dvl-1 was probably a key regulator in the pathway of wnt4/ß-catenin to take part in the vascular restenosis partly, and Dvl-1 is a potential gene to anti- restenosis.

[Effect of tetramethylpyrazine on the proliferation and collagen synthesis of vascular smooth muscle cells].

OBJECTIVE: To study the action mechanism of tetramethylpyrazine (TMP) on the proliferation of vascular smooth muscle cells (VSMCs), thus providing experimental evidence for Chinese medicine to effectively prevent restenosis. METHODS: Rats' thoracic aorta VSMCs in vitro cultured (cell line A7r5) were divided into five groups, i.e., the negative control group, the angiotensin II (Ang II, 10(-6) mol/L) group, the low dose TMP (20 micromol/L) plus Ang II group, the middle dose TMP (40 micromol/L) plus Ang II group, the high dose TMP (80 micromol/L) plus Ang II group. The proliferation ratio was detected by MTT. Gene and protein expressions of Wnt4, Dvl-1, beta-catenin, CyclinD1, and collagen I and III were detected with real-time fluorescent quantitative PCR and Western blot respectively. RESULTS: Compared with the negative control group, the proliferation ratio of VSMCs obviously increased in the Ang II group (P < 0.05). Compared with the Ang II group, the proliferation ratio of VSMCs obviously decreased in the middle dose TMP plus Ang II group and the high dose TMP plus Ang II group (P < 0.05). Compared with the negative control group, gene and protein expressions of Wnt4, Dvl-1, beta-catenin, CyclinD1, Col I, and Col III were obviously up-regulated in the Ang II group (P < 0.05). Compared with the Ang II group, mRNA and protein expressions of Wnt4, Dvl-1, beta-catenin, CyclinD1, Col I, and Col III were obviously down-regulated in the middle dose TMP plus Ang II group and the high dose TMP plus Ang II group (P < 0.05). The aforesaid indices were dose-dependent in the low, middle, and high dose TMP plus Ang II groups. CONCLUSION: TMP inhibited Ang II induced proliferation and collagen secretion of VSMCs through down-regulating Wnt signal pathway.

[Relationship between endothelial-to-mesenchymal transition and cardiac fibrosis in acute viral myocarditis].

OBJECTIVE: To investigate the relationship between endothelial-to-mesenchymal transition (EndMT) and myocardial fibrosis in acute viral myocarditis (VMC). METHODS: Twenty-eight Balb/c mice were randomized into 3 groups: control group (n=8), VMC group(n=10) and intervention group(n=10). Mice in VMC and intervention groups were injected intraperitoneally(i.p) with single dose of coxsackievirus B3, mice in control group were injected with equal amount of viral-free vehicle. In the following day, mice in control and VMC groups were injected i.p with 0.1 ml of saline and intervention group with 0.1 ml of recombinant human bone morphogenetic protein 7(rh-BMP7) at a concentration of 300 µg/kg. The mice hearts were harvested after 7 d, cardiac collagen volume fraction (CVF) was calculated on picrosirius red-stained sections. mRNA and protein expression of TGF-ß1, CD31, VE-cadherin, fibroblast special protein 1 (FSP-1) and α-smooth muscle actin (α-SMA) and collagen 1α1 in myocardiac tissues were detected by real-time RT-PCR and Western blot analysis, respectively. RESULTS: Compared to controls, overt fibrosis was presented in necrotic area of myocardium in VMC group. Meanwhile, marked increase of TGF-ß1 expression accompanied with EndMT characterized by loss of endothelial phenotype (decreased expression of CD31 and VE-cadherin), gain of mesenchymal proteins (overexpression of FSP-1 and α-SMA) and increased synthesis of collagen was also demonstrated. Both EndMT and cardiac fibrosis were simultaneously reversed by TGF-ß1 inhibition. CONCLUSION: EndMT is involved in cardiac fibrosis in acute viral myocarditis, TGF-ß1 might be a main mediator.