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Prognostic Value of Asymmetric Dimethylarginine in Patients with Heart Failure: A Systematic Review and Meta-analysis
Objective. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, is reported to be a risk factor for cardiovascular disease. The purpose of the present study is to investigate whether ADMA is an independent predictor for future mortality and adverse clinical events among patients with heart failure (HF). Methods. Electronic literature databases (Central, MEDLINE, and Embase) were searched for relevant observational studies on the prognostic value of ADMA in HF patients published before January 2019. Pooled hazard ratios (HRs) or odds ratio and the corresponding 95% confidence interval (CI) were calculated for risk evaluation. Results. 10 studies with 2195 participants were identified and analyzed. The pooled HR of composite clinical events for the highest vs. lowest quartiles from categorical variable results was 1.34 (95% CI: 1.15-1.57, , %), which is 1.31 (95% CI: 1.10-1.55, , %) in the subgroup of acute decompensated HF. The pooled HR of composite clinical events from continuous variable results was 1.41 (95% CI: 1.21-1.63, , %), with 0.1 μM increment accounting for the increasing 25% risk for composite adverse clinical events. The pooled HR for all-cause mortality was 2.38 (95% CI: 1.48-3.82, , %) after sensitivity analysis. Two studies reporting the HR of inhospital mortality in HF patients regarded it as a prognostic indicator, with categorical variable HR as 1.26 (95% CI: 1.07-1.84, ) and continuous variable OR as 2.15 (95% CI: 1.17–4.29, ). Conclusions. ADMA is an independent predictor for composite clinical outcomes among HF patients with both short-term and long-term prognostic value.
A Comparative Study on Loadings of the Lower Extremity during Deep Squat in Asian and Caucasian Individuals via OpenSim Musculoskeletal Modelling
Populations of different ethnicities may present different movement capacities and muscular function adaptations. The purpose of this study was to investigate the differences of motion and loading in the lower extremity during dynamic deep squats between Asian and Caucasian individuals using OpenSim modelling technique with a customized squat-specific musculoskeletal model. Twenty-four participants joined the test performing the step-squat test, with right foot stepping side, squatting, and returning. The one-dimensional statistical parametric mapping package was used for statistical analysis. The main findings of the current study were as follows: (1) significant lower squat depth was observed in the Asian individuals, (2) the greater knee range of motion and contact forces were found in the Asian individuals, and (3) the greater ankle contact forces in the Caucasian individuals were notable while performing the deep squat compared to the Asian group. Knowledge found in the current study may provide implication for exercise practitioners and physiotherapists while designing schemes for the prevention of loading accumulation in the lower extremity.
Comprehensive Analyses of miRNA-mRNA Network and Potential Drugs in Idiopathic Pulmonary Arterial Hypertension
Introduction. Idiopathic pulmonary arterial hypertension (IPAH) is a severe cardiopulmonary disease with a relatively low survival rate. Moreover, the pathogenesis of IPAH has not been fully recognized. Thus, comprehensive analyses of miRNA-mRNA network and potential drugs in IPAH are urgent requirements. Methods. Microarray datasets of mRNA and microRNA (miRNA) in IPAH were searched and downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMIs) were identified. Then, the DEMI-DEG network was conducted with associated comprehensive analyses including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis, while potential drugs targeting hub genes were investigated using L1000 platform. Results. 30 DEGs and 6 DEMIs were identified in the lung tissue of IPAH. GO and KEGG pathway analyses revealed that these DEGs were mostly enriched in antimicrobial humoral response and African trypanosomiasis, respectively. The DEMI-DEG network was conducted subsequently with 4 DEMIs (hsa-miR-34b-5p, hsa-miR-26b-5p, hsa-miR-205-5p, and hsa-miR-199a-3p) and 16 DEGs, among which 5 DEGs (AQP9, SPP1, END1, VCAM1, and SAA1) were included in the top 10 hub genes of the PPI network. Nimodipine was identified with the highest CMap connectivity score in L1000 platform. Conclusion. Our study conducted a miRNA-mRNA network and identified 4 miRNAs as well as 5 mRNAs which may play important roles in the pathogenesis of IPAH. Moreover, we provided a new insight for future therapies by predicting potential drugs targeting hub genes.
Unilateral Multifocality and Bilaterality Could Be Two Different Multifocal Entities in Patients with Papillary Thyroid Microcarcinoma
Objective. Multifocality within an affected lobe (unilateral multifocality) or two lobes (bilaterality) is commonly denoted as multifocality without differentiation. Recently, there has been molecular evidence indicating that unilateral multifocality and bilaterality could be two different entities. However, few studies concerning the comparison between these two different multifocality entities have been reported. Design. A retrospective cohort study. Methods. From 2010 to 2013, in total, 949 consecutive patients with papillary thyroid microcarcinoma (PTMC) were enrolled and further divided into four groups based on multifocality status. Unilateral multifocality and bilaterality were analyzed by binary logistic regression along with other clinicopathological factors. Results. Unilateral multifocality, instead of bilaterality, was correlated with central neck metastasis (CNM) in both univariate and multivariate analyses. Group IV (unilateral multifocality and bilaterality coexist) had the highest CNM rate. Group III (unilateral multifocality) had a higher CNM rate than group II (bilaterality, single lesion in each lobe), with a significant difference (). Similar lateral neck metastasis tendency was observed among the four groups. In the multivariate analysis, only unilateral multifocality and bilaterality which coexisted were correlated with CNM. Moreover, 9 cases had a recurrence, with the recurrence rate ranking top in group IV (3.6%), second in group III (2.8%), and third in group II (1.2%). The difference was significant (). Conclusion. Unilateral multifocality and bilaterality could be two different multifocal entities in patients with PTMC. Unilateral multifocality serving as a prognostic factor indicated a worse prognosis than bilaterality on neck metastasis. When the two factors coexisted in PTMC, patients had the highest risk of CNM and possibly local recurrence compared with those with either risk factor alone.
Bafilomycin A1 Accelerates Chronic Refractory Wound Healing in db/db Mice
Numerous studies have reported that autophagy plays an important role in chronic wound healing, and enhancement of autophagic activity impairs cutaneous wound healing. The autophagy inhibitor Bafilomycin A1 (Baf A1) inhibits autophagy by preventing the formation of autophagosomes. This study aimed at elucidating the effect of Bafilomycin A1 on chronic refractory wound healing in diabetic mice. A total of 40 diabetic (db/db) mice and 20 nondiabetic (db/m) mice were used in this study. Full-thickness skin defects were generated in the db/db mice models, which were then divided into the following two groups: the nontreated (db/db group) and Baf A1-treated groups (Baf A1 group). The same skin defects were generated in db/m mice (db/m group) to serve as a control. We demonstrated that Baf A1 treatment significantly accelerated wound healing in db/db mice and exerted good healing effects. Moreover, Baf A1 inhibited autophagy in the newly generated epidermis and had minor effects on metabolism in db/db mice. PCNA expression, as detected by immunohistochemistry, and collagen thickness, as detected by Masson’s trichrome staining on the 14th day, were higher in the db/m and Baf A1 groups than in the db/db group. In addition, the expression of the proinflammatory cytokine TNF-α in the db/m and Baf A1 groups increased significantly on day 6, and the expression of the anti-inflammatory cytokine IL-10 also increased significantly on day 9. However, there were no significant changes in the expression levels of TNF-α and IL-10 in the db/db group. Therefore, Baf A1 may accelerate diabetic chronic refractory wound healing by promoting cell proliferation, collagen production, and regulating the inflammatory balance.
miR-214-3p Attenuates Sepsis-Induced Myocardial Dysfunction in Mice by Inhibiting Autophagy through PTEN/AKT/mTOR Pathway
Aims. More than half of the patients with sepsis would develop cardiac dysfunction, which is termed as sepsis-induced myocardial dysfunction (SIMD). Previous studies suggest that autophagy may play an important role in SIMD. The present study investigated whether miR-214-3p could attenuate SIMD by inhibiting autophagy. Main Methods. In this article, we investigated the role of autophagy in a mouse model of cecal ligation and puncture (CLP). The structure and function of hearts harvested from the mice were evaluated. Myocardial autophagy levels were detected with immunohistochemical, immunofluorescent, and Western blot. Key Findings. miR-214-3p can alleviate SIMD in septic mice by inhibiting the level of cardiac autophagy to attenuate myocardial dysfunction. Moreover, this study showed that miR-214-3p inhibited autophagy by silencing PTEN expression in the myocardial tissues of septic mice. Significance. This study showed that miR-214-3p attenuated SIMD through myocardial autophagy inhibition by silencing PTEN expression and activating the AKT/mTOR pathway. The present findings supported that miR-214-3p may be a potential therapeutic target for SIMD.