This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

OBJECTIVE:To study antibacterial activities of meropenem(MPN)combined with cefoperazone sulbactam(SCF) to 3 kinds of multidrug resistance (MDR) Gram-negative bacteria. METHODS:Each 50 strains of MDR-Escherichia coli (MDR-EC),MDR-Klebsiella pneumoniae (MDR-KPN) and MDR-Acinetobacter baumannii (MDR-AB) were isolated from spu-tum,blood,urine,ascites or drainage specimens of patients during Jan. to Dec. in 2016 from the affilidated hospital of Taishan medical university. The agar dilution method and board method were used to determine MIC50,MIC90 and MICG of MPN,SCF, MPN+SCF to MDR-EC,MDR-KPN,MDR-AB and calculate fractional inhibitory concentration (FIC). Drug sensitivity test was conducted by K-B disk method. RESULTS:In terms of the MICG to MDR-EC,MDR-KPN,MDR-AB,MPN alone were respec-tively 36.82,82.45,34.32 μg/mL;SCF alone were respectively 42.14,112.67,24.11 μg/mL;MPN combined with SCF were re-spectively 25.97,56.64,11.36 μg/mL. In terms of MICG to MDR-EC,MDR-KPN,MICG showed that MPN+SCF0-0.5 (78.00%),>0-0.5(72.00%),>0.5-1.0 (82.00%). CONCLUSIONS:MPN combined with SCF can effectively improve antibacterial activities to MDR Gram-negative bac-teria as MDR-EC,MDR-KPN,MDR-AB. MPN combined with SCF has synergistic effects.

Objective To screen and isolate the radioresistance related genes of IRM-2 mice.Methods cDNA library of IRM-2 mice was constructed by SMART technique.Total RNA was isolated from spleens of IRM-2 male mice.The first-strand cDNA was synthesized by using PowerScript reverse transeriptase,and double-strand cDNA was synthesized and amplified by long PCR.The PCR products were purified,digested with restriction enzyme Sfi I.The ds-cDNA fragment lessthan 500 bp was fractionated and ligated to the Sfi I-digested pDNR-LIB vector.The ligation mixture was transformed into E.coil DH5α by electroporution transformation to generate the unamplified cDNA library.The quality of cDNA library was identified by PCR technique.130 clones from cDNA library were sequenced and compared with GenBank database.Results The cDNA library contained 2.25 x 106 independent clones with an average insert size of 1.2 kb.The ratio of recombination and full-length was 95% and 55%,respectively.21 pieces of EST sequences from cDNA library were not the same as the known mice genes and registered into GenBank EST database,with registered number DW474856-DW474876.Conclusions cDNA library of IRM-2 mice has been constructed successfully.21 pieces of EST implies that radioresistance correlative genes may be in IRM-2 mice,which will lay a foundation for isolating and identifying radioresistance related genes in further study.