The prevalence of obstructive sleep apnea in interstitial lung disease: a systematic review and meta-analysis

Sleep and Breathing - To evaluate the overall prevalence of obstructive sleep apnea (OSA) in interstitial lung disease (ILD). We performed a systematic search of the academic literature while...     

Smad4 deficiency substitutes Cdkn2b but not Cdkn2a downregulation in pancreatic cancer following induction of genetic events in adult mice

BackgroundMinor progress in pancreatic cancer treatment and prognosis implies that more reliable animal models are urgently needed to decipher its molecular mechanisms and preclinical research. We recently reported a genetically engineered adult mouse model where Cdkn2b downregulation was required together with Cdkn2a downregulation to inactivate the Rb pathway. Besides, the role of Smad4, which is mutated more frequently than Cdkn2b in human pancreatic cancer, was determined critical on the development of the pancreas tumor by some reports. However, the impact of Smad4 deficiency in combination with PDAC-relevant mutations, such as Cdkn2a when induced in adult pancreas has not been completely elucidated in mice.MethodsLentiviral delivered oncogene/tumor suppressors in adult pancreas. The development of pancreatic cancer was monitored. Hematoxylin and eosin staining and immunofluorescence were performed for pathological identification of the pancreatic cancer. Real-time polymerase chain reaction, immunofluorescence and western blot were used to test gene expression.ResultsLoss of Smad4 could cooperate with alterations of KRAS, Trp53, and Cdkn2a to induce pancreatic cancer in adult mice. The role of Smad4 was mainly in downregulating the expression of Cdkn2b and further inducing phosphorylation of the Rb1 protein.ConclusionsThese findings show an essential role of Smad4 deficiency in pancreatic ductal adenocarcinoma (PDAC) formation. This model better recapitulates the adult onset, clonal origin, and genetic alterations in human PDAC and can be simply generated on a large-scale.     

经导管主动脉瓣置换术后冠状动脉阻塞研究进展

经导管主动脉瓣置换术为重度主动脉瓣狭窄的一线治疗手段。冠状动脉（冠脉）阻塞是经导管主动脉瓣置换术相关的严重并发症之一,一旦发生死亡率极高。本文就经导管主动脉瓣置换术后冠脉阻塞的发生机制、危险因素、临床表现、特殊人群的冠脉阻塞及预防和处理措施进行阐述。     

In Vitro Functional Assessment of 22 Newly Identified CYP2D6 Allelic Variants in the Chinese Population

Cytochrome P450 2D6 (CYP2D6) is one of the most widely investigated CYPs related to genetic polymorphisms and is responsible for one‐quarter of the currently used clinical drugs. We previously detected 22 novel, non‐synonymous, mutated sites in the Chinese population, but nothing is known about the functional effects of these mutations in terms of specific CYP2D6 substrates. In this study, wild‐type CYP2D6, two common allelic variants and 22 newly reported CYP2D6 isoforms were transiently expressed in 293FT cells, and the enzymatic activities of these variants were systematically assessed using dextromethorphan and bufuralol as the probing substrates. Consequently, 19 and 21 allelic variants were found to exhibit significantly decreased enzymatic activities for dextromethorphan and bufuralol, respectively. Of 22 novel CYP2D6 variants, six allelic isoforms (CYP2D6.89, CYP2D6.92, CYP2D6.93, CYP2D6.96, E215K and R440C) exhibited absent or extremely reduced metabolic activities compared with those observed for the wild‐type enzyme. Our in vitro functional data can be useful for CYP2D6 phenotype prediction and provide valuable information for the study of clinical impact of these newly found CYP2D6 variants in China.     

Hybrid Molecule from Farnesylthiosalicylic Acid-diamine and Phenylpropenoic Acid as Ras-related Signaling Inhibitor with Potent Antitumor Activities

Novel series of Farnesylthiosalicylic acid-diamine/phenylpropenoic acid hybrids were designed and synthesized. Their in vitro growth inhibitory assays showed that most compounds displayed strong antiproliferation activity against seven cancer cells. Especially, the new hybrid 12f , by the conjugation of 10a with ferulic acid, could selectively suppress the proliferation of tumor cells and display significantly lower toxicities to normal cells than its intermediate 10a . Furthermore, 12f dose-dependently induced SMMC-7721 cell apoptosis. Additionally, our observations demonstrated that 12f inhibited both Ras-related signaling and phosphorylated NF-κB synergistically, which may be advantageous to the strong antitumor activities of 12f . Our findings suggest that these novel hybrids may hold a great promise as therapeutic agents for the intervention of human cancers.     

人工智能技术在MSCT肺结节诊断中的应用

人工智能(artificial intelligence,AI)是当前科学技术发展中的一门前沿学科[1],被定义为精准医疗的典范,其强大的后处理能力和进一步学习、分析能力逐渐得到业界的认可,它广泛应用于医学领域,在临床医学影像诊断中、特别是在肺部小结节的诊断应用已日渐增多,但临床应用方面的有关报道仍较少。近年来,我院在肺部小结节、冠状动脉血管成像以及颅内血肿诊断等方面的MSCT影像诊断也在不断尝试应用。相信在不久的将来,以人工智能技术为主导的新潮流[2],必将为医学影像诊断带来新机遇。本文有关肺部结节MSCT应用的认识进行分析,供同道参考。     

Rapid decoloration of azo dye Direct Blue 6 by AlCrFeMn high entropy alloy

In recent years, high entropy alloys (HEAs) have attracted a lot of attention from researchers due to their outstanding mechanical properties, but there are few reports about their functional performance. The development of new functional applications of HEAs is a challenging, but very meaningful topic. The decoloration of azo dye Direct Blue 6 (DB6) using equiatomic AlCrFeMn HEA synthesized by ball-milling is reported in this study. Ball-milled (BM) AlCrFeMn HEA shows excellent performance in the decoloration of DB6, 3 times faster than BM MgZn-based glassy powders and AlCoCrTiZn HEA, which are reported as the best among the metallic glasses and HEAs so far, respectively. The effects of initial pH, initial temperature and dye concentrations on the decoloration efficiency during reaction are systematically studied. This work can greatly expand the applications of HEAs, especially the application of their functional properties.

In recent years, high entropy alloys (HEAs) have attracted a lot of attention from researchers due to their outstanding mechanical properties, but there are few reports about their functional performance.     

Prediction of the tissue-specificity of selective estrogen receptor modulators by using a single biochemical method

Here, we demonstrate that a single biochemical assay is able to predict the tissue-selective pharmacology of an array of selective estrogen receptor modulators (SERMs). We describe an approach to classify estrogen receptor (ER) modulators based on dynamics of the receptor-ligand complex as probed with hydrogen/deuterium exchange (HDX) mass spectrometry. Differential HDX mapping coupled with cluster and discriminate analysis effectively predicted tissue-selective function in most, but not all, cases tested. We demonstrate that analysis of dynamics of the receptor-ligand complex facilitates binning of ER modulators into distinct groups based on structural dynamics. Importantly, we were able to differentiate small structural changes within ER ligands of the same chemotype. In addition, HDX revealed differentially stabilized regions within the ligand-binding pocket that may contribute to the different pharmacology phenotypes of the compounds independent of helix 12 positioning. In summary, HDX provides a sensitive and rapid approach to classify modulators of the estrogen receptor that correlates with their pharmacological profile.