Myocardial fibrosis is an important part of cardiac remodeling that leads to heart failure and death. Myocardial fibrosis results from increased myofibroblast activity and excessive extracellular matrix deposition. Various cells and molecules are involved in this process, providing targets for potential drug therapies. Currently, the main detection methods of myocardial fibrosis rely on serum markers, cardiac magnetic resonance imaging, and endomyocardial biopsy. This review summarizes our current knowledge regarding the pathophysiology, quantitative assessment, and novel therapeutic strategies of myocardial fibrosis.

Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults. In spite of advances in diagnosis and therapy, the prognosis of patients with GBM has remained dismal. The fast recurrence and multi-drug resistance are some of the key challenges in combating brain tumors. Glioma stem cells (GSCs) which are considered the source of relapse and chemoresistance, the need for more effective therapeutic options is overwhelming. In our present work, we found that combined treatment with temozolomide (TMZ) and metformin (MET) synergistically inhibited proliferation and induced apoptosis in both glioma cells and GSCs. Combination of TMZ and MET significantly reduced the secondary gliosphere formation and expansion of GSCs. We first demonstrated that MET effectively inhibited the AKT activation induced by TMZ, and a combination of both drugs led to enhanced reduction of mTOR, 4EBP1 and S6K phosphorylation. In addition, the combination of the two drugs was accompanied with a powerful AMP-activated protein kinase (AMPK) activation, while this pathway is not determinant. Xenografts performed in nude mice demonstrate in vivo demonstrated that combined treatment significantly reduced tumor growth rates and prolonged median survival of tumor-bearing mice. In conclusion, TMZ in combination with MET synergistically inhibits the GSCs proliferation through downregulation of AKT-mTOR signaling pathway. The combined treatment of two drugs inhibits GSCs self-renewal capability and partly eliminates GSCs in vitro and in vivo. This combined treatment could be a promising option for patients with advanced GBM.

Aims Conventional fractional flow reserve (FFR) is measured invasively using a coronary guidewire equipped with a pressure sensor. A non-invasive derived FFR would eliminate risk of coronary injury, minimize technical limitations, and potentially increase adoption. We aimed to evaluate the diagnostic performance of a computational pressure-flow dynamics derived FFR (caFFR), applied to coronary angiography, compared to invasive FFR. Methods and results The FLASH FFR study was a prospective, multicentre, single-arm study conducted at six centres in China. Eligible patients had native coronary artery target lesions with visually estimated diameter stenosis of 30–90% and diagnosis of stable or unstable angina pectoris. Using computational pressure-fluid dynamics, in conjunction with thrombolysis in myocardial infarction (TIMI) frame count, applied to coronary angiography, caFFR was measured online in real-time and compared blind to conventional invasive FFR by an independent core laboratory. The primary endpoint was the agreement between caFFR and FFR, with a pre-specified performance goal of 84%. Between June and December 2018, matched caFFR and FFR measurements were performed in 328 coronary arteries. Total operational time for caFFR was 4.54 ± 1.48 min. caFFR was highly correlated to FFR (R = 0.89, P = 0.76) with a mean bias of −0.002 ± 0.049 (95% limits of agreement −0.098 to 0.093). The diagnostic performance of caFFR vs. FFR was diagnostic accuracy 95.7%, sensitivity 90.4%, specificity 98.6%, positive predictive value 97.2%, negative predictive value 95.0%, and area under the receiver operating characteristic curve of 0.979. Conclusions Using wire-based FFR as the reference, caFFR has high accuracy, sensitivity, and specificity. caFFR could eliminate the need of a pressure wire, technical error and potentially increase adoption of physiological assessment of coronary artery stenosis severity. Clinical Trial Registration URL: http://www.chictr.org.cn Unique Identifier: ChiCTR1800019522.

BackgroundThis study is a systematic review and meta-analysis of the diagnostic value of cardiovascular magnetic resonance (CMR) in cardiac amyloidosis (CA).MethodsA wide variety of electronic databases were searched for studies of CMR that reported the diagnostic accuracy in patients with suspected CA. Research manuscripts were subjected to further systematic review and meta-analysis. Methodological evaluation was performed under the guidance of the Quality Assessment of Diagnostic Accuracy Studies −2 (QUADAS–2). Heterogeneity was assessed, and a random-effects model was used to assess the diagnostic effects of CMR on pooled sensitivity, pooled specificity, and summary receiver operating characteristics (SROC).ResultsSeven studies that reported the performance of CMR for CA were included in the present systematic review, among which five studies (257 patients) that evaluated the diagnostic accuracy of late gadolinium enhancement (LGE) CMR were analyzed in the present meta-analysis. Heterogeneity was observed only in specificity. A summary sensitivity and specificity of 85 % (95 % CI: 77–91 %) and 92 % (95 % CI: 83–97 %) indicated a high diagnostic accuracy of LGE for CA. The AUC of SROC curve was 0.9530, suggesting that LGE is an effective way of diagnosing patients with possible cardiac involvement in amyloidosis.ConclusionsLGE–CMR seems to have a relatively high diagnostic accuracy for amyloidosis patients with possible cardiac involvement. Combined CMR techniques may provide important information for the selection of suitable therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0311-6) contains supplementary material, which is available to authorized users.