Objective To evaluate the effect of methylprednisolone on endoplasmic reticulum stress in rats with ventilator-induced lung injury ( VILI ) and the relationship with phosphatidylinositol 3-kinase∕serine-threonine protein kinase ( PI3K∕Akt) signaling pathway. Methods One hundred clean-grade male Sprague-Dawley rats, aged 4-5 months, weighing 270-320 g, were divided into 5 groups ( n=20 each) using a random number table method: control group ( C group) , VILI group ( V group) and different doses of methylprednisolone groups ( M1-3 groups) . Group C received no mechanical ventilation and kept spontane-ous breathing for 4 h. Rats were mechanically ventilated ( tidal volume 40 ml∕kg, respiratory rate 15-17 breaths∕min, inspiratory∕expiratory ratio 1 : 1, positive end-expiratory pressure 0, fraction of inspired oxy-gen 21％ during OLV) in group V. Methylprednisolone 2, 10 and 30 mg∕kg were intravenously injected at 20 min before mechanical ventilation in M1-3 groups, respectively, and the equal volume of normal saline was given in group V. Blood samples and lung tissues were taken at 4 h of ventilation for measurement of the lung permeability index ( LPI) and wet∕dry lung weight ratio ( W∕D ratio) , for examination of pathological changes, and for determination of apoptosis index ( AI) in lung tissues ( by TUNEL) , expression of Akt, phosphorylated Akt (p-Akt), glucose-regulated protein 78 (GRP78), CCAAT∕enhancer-binding protein homologous protein (CHOP) and caspase-12 in lung tissues (by Western blot). Injured alveoli rate (IAR) was calculated. Results Compared with group C, the W∕D ratio, LPI, IAR and AI were significantly in-creased, the expression of p-Akt was down-regulated, and the expression of GRP78, CHOP and caspase-12 was up-regulated in V and M1 groups ( P<0. 05) , and no significant change was found in the indexes mentioned above in M2 and M3 groups ( P>0. 05) . Compared with group V, the W∕D ratio, LPI, IAR and AI were significantly decreased, p-Akt expression was up-regulated, and the expression of GRP78, CHOP and caspase-12 was down-regulated in M2 and M3 groups ( P<0. 05) . Conclusion Methylprednisolone in-hibits endoplasmic reticulum stress, thus inhibiting cell apoptosis, and the mechanism is related to activa-ting PI3K∕Akt signaling pathway in rats with VILI.

Mouse double minute 2 (Mdm2) gene was isolated from a cDNA library derived from transformed mouse 3T3 cells, and was classified as an oncogene as it confers 3T3 and Rat2 cells tumorigenicity when overexpressed. It encodes a nucleocytoplasmic shuttling ubiquitin E3 ligase, with its main target being tumor suppressor p53, which is mutated in more than 50% of human primary tumors. Mdm2's oncogenic activity is mainly mediated by p53, which is activated by various stresses, especially genotoxic stress, via Atm (ataxia telangiectasia mutated) and Atr (Atm and Rad3-related). Activated p53 inhibits cell proliferation, induces apoptosis or senescence, and maintains genome integrity. Mdm2 is also a target gene of p53 transcription factor. Thus, Mdm2 and p53 form a feedback regulatory loop. External and internal cues, through multiple signaling pathways, can act on Mdm2 to regulate p53 levels and cell proliferation, death, and senescence. This review will focus on how Mdm2 is regulated under genotoxic stress, and by the Akt1-mTOR-S6K1 pathway that is activated by insulin, growth factors, amino acids, or energy status.
3T3 Cells ; Animals ; Apoptosis ; Cell Proliferation ; Cellular Senescence ; DNA Damage ; Energy Metabolism ; Feedback, Physiological ; Gene Library ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Mice ; Molecular Targeted Therapy ; Mutation ; Neoplasms ; genetics ; metabolism ; Proto-Oncogene Proteins c-mdm2 ; genetics ; metabolism ; Ribosomal Protein S6 Kinases, 90-kDa ; genetics ; metabolism ; Signal Transduction ; genetics ; TOR Serine-Threonine Kinases ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Ubiquitin-Protein Ligases ; genetics ; metabolism

Objective To study the application of strain ratio in differentiation of benign and malignant thyroid nodules through analyzing the influencing factors of the elastic strain ratio (SR) of thyroid nodules.Methods There were 468 patients with 476 thyroid nodules in present study, who came from the Nanjing Drum Tower Hospital from January 2012 to February 2014. SR characteristics of thyroid nodules were retrospectively analyzed, and the critical values were found by receiver-operating characteristic (ROC) curve. Then the size, echo, calcification, blood flow and the correlation between SR and pathology were analyzed by Pearson bivariate correlation analysis.Results The ROC curve showed that SR=0.5 was the best threshold value of SR in differential diagnosis of benign and malignant thyroid nodules. The diagnostic sensitivity, specificity, and the area under the curve were 84.8％, 85.9％, and 0.894, respectively. SR was negatively correlated with echo and calcification, while positively correlated with nodule size and blood flow (r=0.158,P=0.001;r=-0.209,P=0.000;r=-0.218,P=0.000;r=0.189,P=0.000;r=-0.519,P=0.000). The pathology of thyroid nodules had no correlation with nodule size and blood flow (r=-0.025,P=0.582;r=-0.070,P=0.126). The pathology was positively correlated with echo and calcification, while negatively correlated with age (r=0.265,P=0.000;r=0.185,P=0.000;r=-0.207,P=0.000;r=-0.519,P=0.000). Conclusion To improve the accuracy of diagnosis, the differential diagnosis of benign and malignant thyroid nodules should be based on two-dimensional ultrasound combined with SR and fine needle aspiration.