Objective: To discover molecular markers associated with lung adenocarcinoma diagnosis/prognosis and drug resistance through screening of differentially expressed genes based on published chip data in gene expression databases using bioinformatics methods. Methods: Comprehensive analysis was performed in available mRNA microarray datasets including lung adenocarcinoma tissues dataset GSE32863 and lung adenocarcinoma taxane-platin resistance dataset GSE77209 from the gene expression omnibus(GEO) database. Gene ontology enrichment analysis, gene pathway enrichment analysis and protein interaction network analysis were performed based on significantly correlated genes. The expression level of genes was validated in the cancer genome atlas(TCGA) dataset. Survival differences were assessed by the log-rank test in TCGA lung adenocarcinoma dataset. Based on the publications genomics of drug sensitivity in cancer(GDSC) database in CellMiner cross database(CellMiner CDB), Pearson correlation analysis was used to analyze the correlation between differentially expressed genes and the half-maximal inhibitory concentration(IC50) of anticancer drugs. Results : There were a total of 77 genes which had a different expression in resistance lung adenocarcinoma cells and lung adenocarcinoma cancer tissues. The functional enrichment analysis showed that these co-different expression genes were mainly enriched in microtubule, extracellular exosome, cell cycle and signaling by nuclear receptors. Protein-protein interactions(PPI) network screened 6 most connected genes as molecular complex(MCODE). Among the MCODE, overexpressed ubiquitin conjugating enzyme E2 T(UBE2T), kinesin family member 20A(KIF20A), PCNA clamp associated factor(KIAA0101), pituitary tumor-transforming gene 1(PTTG1) and NIMA related kinase 2(NEK2) were associated with poor outcomes. Survival analysis results showed that these five genes were upregulated in lung adenocarcinoma tissues and drug-resistant cells and were significantly associated with poor prognosis in lung adenocarcinoma patients. Drug sensitivity analysis results suggested that high expression of PTTG1 and UBE2T was significantly associated with sensitivity to multiple anticancer drugs, including paclitaxel and docetaxel. RT-PCR validation showed that PTTG1 andUBE2T were highly expressed in docetaxel-resistant cells A549-TXR and H358-TXR. Conclusion PTTG1 andUBE2T holds the potential to be chemoresistance markers in lung adenocarcinoma.

Objective:To compare the safety and efficacy of domestic Firebird2 TM rapamycin eluting stent and imported Endeavor Resolute stent in the treatment of coronary heart disease patients. Methods:The clinical data of 889 patients with coronary heart disease who underwent percutaneous coronary intervention (PCI) in Wuhan Asian heart hospital from 2010 to 2015 were analyzed retrospectively A case-control study was conducted. According to the type of stent used, 550 cases were divided into domestic Firebird 2TM group and 325 cases were divided into imported endeavor resolve group The incidence of major adverse cardiovascular events (MACE) was compared between the two groups. All patients was followed up for 1 year.Results:There was no significant difference in gender, age, body mass index, medical diseases, whether it was emergency PCI, previous PCI history, coronary artery bypass grafting history and left ventricular between the two groups (all P>0.05). The success rate of PCI in the two groups was 100%. The TIMI blood flow of target vessels in the two groups was grade 3. There was no stent unloading during the operation, and balloon pretreatment and post-treatment were performed. The results of one-year follow-up showed that there was no significant difference in the incidence of mace (3.1% (17/550) and 2.2%(7/325)) and the incidence of independent end points between domestic Firebird 2 TM group and endeavor group (all P>0.05); There was no significant difference in survival without mac between the two groups ( P>0.05). Conclusion:The domestic Firebird2 TM rapamycin eluting stent has the same clinical efficacy as the imported Endeavor Resolute drug eluting stent.

Objective: To explore the relationship between anthropometric indices and the incident risk of hypertension, compare novel anthropometric indices with traditional indices in hypertension prediction and establish hypertension prediction models among elderly Chinese. Methods: A total of 27 009 retirees from the Dongfeng Motor Corporation were recruited at baseline in 2008 and the first follow-up was conducted in 2013. After the exclusion of participants less than 60 years old, participants with hypertension, coronary heart disease, stroke, cancer, and those with missing data, a total of 6 784 elderly participants were enrolled in this study. A multivariate logistic regression model was used to analyze the relationship between traditional anthropometric indices, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), novel anthropometric indices, visceral adiposity index (VAI), body shape index (ABSI), body roundness index (BRI), and the incident risk of hypertension. Meanwhile, a multivariate logistic regression model was used to establish hypertension prediction models. Receiver operating characteristic (ROC) curve was applied to compare the prediction ability of different models. Results: A total of 1 787 incident cases of hypertension were identified, with the incidence of hypertension about 27.59%. Significant positive associations were detected between BMI, WC, WHtR, VAI, BRI and the incident risk of hypertension after adjusting for potential confounders (all P values<0.05). In men, the OR (95%CI) (upper tertile vs lower tertile) was 1.45 (1.22-1.73) for VAI, and 1.86 (1.55-2.23) for BRI. In women, the OR (95% CI) (upper tertile vs lower tertile) was 1.55 (1.22-1.96) for VAI, and 1.60 (1.27-2.01) for BRI. For ABSI, no significant association was observed in either men (OR (95%CI): 1.07 (0.90-1.28)) or women (OR (95%CI): 1.03 (0.82-1.29), both P values >0.05). The basic hypertension prediction model included age, drinking (only in men), education status (only in men), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting blood glucose levels. Based on the basic prediction model, BMI (in men: AUC=0.697) and BRI (only in men: AUC=0.696) improved area under ROC curve (AUC) significantly (P<0.05). BMI was the strongest predictor in both men (AUC=0.697) and women (AUC=0.685) in the extended model. Conclusion Significant positive associations were detected between BMI, WC, WHtR, VAI, BRI and the incident risk of hypertension among elderly Chinese. BMI was the strongest predictor in hypertension prediction model compared with other anthropometric indices.

Objective To compare the prognosis of vascular in situ and bridge vessel percutaneous coronary intervention ( PCI) therapy strategies in patients with recurrent angina after coronary artery bypass grafting ( CABG) . Methods A total of one hundred and two patients with recurrent angina after CABG from January 2008 to January 2016 were involved in this study and were divided into two groups according to interventional therapy strategy:74 patients in the vascular in situ PCI group ( in situ group,74 cases) and 28 patients for bridge vessel PCI group ( bridge vessel group,28 cases) . The patients have been followed up for (33. 6± 10. 2) months. The major adverse cardiovascular events ( MACE) of the two groups were recorded, including non?fatal acute myocardial infarction ( AMI) ,target vessel revascularization ( TVR) and cardiac death, and multivariate logistic regression analysis was used to analyze the related factors of MACE. Results Compared with the bridge vessel group,the non?MACE survival rate,non?AMI survival rate and non?TVR survival rate of the in situ group were significantly increased ( ( 71. 6% ( 53/74 ) vs. 57. 1% ( 16/28 ) , 93. 2% ( 69/74 ) vs. 82. 1% (23/28),81. 1% (60/74) vs. 67. 9% (19/28) ),the differences were statistically significant (χ2=8. 141,4. 219,5. 436, P<0. 05) . Multivariable logistic regression analysis showed that age of bridge ( OR=1. 023,95%CI 1. 005-1. 026,P=0. 019) ,diabetes mellitus ( OR=2. 386,95%CI 1. 425-3. 991,P=0. 003) and bridge vessel PCI (OR=1. 884,95%CI 1. 093-3. 220,P=0. 025) were factors that affect the clinical prognosis in patients with recurrent angina pectoris after CABG. Conclusion The clinical prognosis of the in situ PCI is better than bridge vascular PCI in patients with recurrent angina after CABG,while the age of bridge, diabetes mellitus, vascular interventional treatment are factors for the effect of interventional therapy patients prognosis. The clinical prognosis is much better in native vessel PCI than that of bridge vessel PCI in patients with recurrent angina after CABG. The age of bridge,diabetes mellitus and bridge vessel PCI are the factors that affect the clinical prognosis in the patients.

Objective Nrf2 is an important neuroprotective factor and the ubiquitin proteasome system ( UPS) , as a highly specific intracellular protein degradation pathway, plays an important role in maintaining gene and protein functions.This paper pres-ents a preliminary study on the relationship between Nrf2 and the ubiquitin proteasome system in the mouse model of traumatic brain in-jury ( TBI) . Methods Forty-two healthy male ICR mice were randomly divided into three groups: control, TBI +sulforaphane ( SFN) and TBI+vehicle, and 12 Nrf2-knockout mice were included in the TBI+Nrf2 -/-group.The animals of the TBI+SFN group were treated with SFN while those of the TBI+vehicle group with the same volume of 10%corn oil at 5 minutes after TBI.At 24 hours after TBI, brain samples were collected from the mice for determining the Nrf2 expression and ubiquitinated protein content by Western blot and the changes in the Nrf2 and ubiquitinated proteins were observed by immunohistochemistry and electron microscopy. Results Compared with the controls, the mice in the TBI+vehicle group showed significantly increased expressions of Nrf2 ( 0.09 ± 0.02 vs 0.66 ±0.09, P<0.05) and ubiquitinated proteins (3.27 ± 0.21 vs 10.58 ±0.75, P<0.05).In comparison with animals in the TBI+vehicle group, those in the TBI+SFN group exhibited a signifi-cant increase in the Nrf2 protein level (0.66 ±0.09 vs 1.22 ±0.14, P<0.05) but a decrease in the ubiquitinated protein level (10.58 ±0.75 vs 6.97 ±0.86, P<0.05), and those in the TBI+Nrf2 -/-group showed a markedly decreased expression of the Nrf2 protein (0.66 ±0.09 vs 0.17 ±0.02, P<0.05) but increased expression of the ubiquitinated protein (10.58 ±0.75 vs 14.35 ± 0.65, P<0.05).Similar results were observed by immunohistochemistry and electron microscopy. Conclusion Nrf2 played a neu-roprotective role in the mouse model of traumatic brain injury by regulating the ubiquitin proteasome system.

Objective To explore the application of bumetanide to inhibition of tumor cell proliferation.Methods In different cell lines, the expression of natrium,kalium, chloride cotransporter 1 ( NKCC1) was detected by Western blotting while the proliferation of different tumor cells was examined by CCK-8 kit.Results The target protein NKCC1 expression in lung cancer cell line ( A549 ) and colorectal cancer cell line ( HCT116 ) was significantly higher than that in chronic myelogenous leukemia cell line (K562), esophageal cancer cell line (Eca109), cervical carcinoma cell line (HeLa), T lymphocytic leukemia cell line (Jurkat) and breast cancer cell line (MCF7).IC50 Values of bumetanide were significantly lower in A549 and HCT116 than in K562, Eca109,HeLa,Jurkat and MCF7.Furthermore, the inhibiory rate and the target protein expression level were positively correlated.Conclusion Bumetanide can inhibit tumor cell proliferation and NKCC1 can serve as a potential target of anticancer drugs.

Objective To investigate the preoperative and intraoperative assessed values of the color-coded digital subtraction angiography (DSA ) for intracranial arteriovenous malformation (AVM). Methods Fifteen patients with AVM performed preoperative routine whole brain DSA were analyzed retrospectively,and the iFlow software was used to perform color-coded DSA of image post-processing. A comprehensive analysis such as the range of lesions,vascular architecture and hemodynamics of AVM was conducted on the two-dimensional DSA images and color-coded DSA. Results Of the 15 patients with AVM,9 were small-sized (including 4 nidi showed diffuse type),3 were medium-sized,and 3 were large-sized;8 patients had single feeding artery,and 7 had multiple feeding arteries;11 had single draining vein,and 4 had multiple draining veins. When showing the size of AVM nidus,particularly diffuse type nidus, the color-coded DSA was clearer than the two-dimensional image. The color-coded DSA could visually display the traveling of the superficial and deep draining veins,at the same time,the primary and secondary draining veins could be identified according to the size of the area under the curve and the full width at half maximum,and intuitively reflected the complete cycle of cerebral blood flow. Conclusion The color-coded DSA can quickly and accurately depict the range of AVM,angioarchitecture features and intraoperative hemodynamic changes.

Objective The prognosis of traumatic brain injury is closely associated with the apoptosis of neural cells .This study investigated the anti-apoptosis effect of alpha lipoic acid (α-LA) and its possible mechanism in the mouse model of traumatic brain injury. Methods Seventy-two healthy male ICR mice were randomly divided into four groups of 18 each:sham operation +vehicle, sham operation +α-LA, trauma +vehicle, and trauma +α-LA.The model of traumatic brain injury was made by weight-dropping.The animals in the α-LA groups were treated with intragastric α-LA at 30 minutes after surgery, while those in the vehicle groups with oral dimethyl sulfoxide in corn oil .At 48 hours after treatment , brain samples were collected from the mice for determining brain edema , measuring the expressions of cytochrome c , Bcl-2-associated X protein ( Bax ) , and caspase-3 in the mitochondria and cytosol of the brain tissue by Western blot and immunohistochemistry respectively , and detecting the survival of the neurons and apoptosis of neural cells in the cortical area by Nissl staining and TUNEL , re-spectively. Results The brain water volume , caspase-3 expres-sion, and neural cell apoptosis were markedly higher while the neuron survival remarkably lower in the trauma +vehicle group than in the sham operation +vehicle and sham operation +α-LA groups ( P<0.01).Compared with the mice in the trauma +vehicle group, those in the trauma +α-LA group showed significantly reduced proportion of water in the brain tissue ([79.89 ±0.55] vs [81.71 ± 0.66]%, P<0.05), expression of caspase-3 ([58.40 ±7.31] vs [47.42 ±7.74]%, P<0.05), and apoptosis of neural cells ([59.63 ±8.61] vs [44.86 ±7.32]%, P <0.05), but increased survival rate of neurons ([44.45 ±10.56] vs [57.46 ± 11.01]%, P<0.05).The expression of cytochrome c in the mitochondria was remarkably decreased and that of Bax markedly in -creased in the trauma +vehicle than in the sham operation +vehicle and sham operation +α-LA groups (P<0.01). Conclusion Alpha lipoic acid has a protective effect against traumatic brain injury in mice , probably by inhibiting the apoptosis of neural cells through the mitochondrial pathway .

Objective Subarachnoid hemorrhage ( SAH) is a devastating disease with high fatality and morbidity and micro-glia/macrophage ( M/M) plays a vital role in SAH brain injury with complicated pathophysiological mechanism .This study was to ob-serve the effect of Nrf2 deficiency on M/M activation and M1 polarization after subarachnoid hemorrhage in mice . Meth ods We col-lected 70 wild-type ( WT) ICR mice and 35 Nrf2-knockout ( KO) mice to establish the SAH model by injecting fresh autologous blood into pre-chiasmatic cistern.WT mice were arranged into four groups: sham operation group, post operative day 1 (POD1) group, POD3 group and POD5 group.Then WT mice and Nrf2 Nrf2-knockout mice were divided into sham operation WT group , sham opera-tion KO group, SAH WT group and SAH KO group.Western blotting (WB) and immunohistochemistry (IHC) were applied to observe the activation and proliferation of M/M after SAH on WT mice .Difference in activation and M 1 polarization were observed by detecting Iba1 expression in WB and CD 16/32 +Iba1 +cells in immunofluorescence between WT and KO mice . Results Gray scale values of Iba1 expression by WB in WT mice are 0.491 ±0.039, 0.657 ± 0.069, 0.930 ±0.046 and 0.926 ±0.046;average optical intensity values of Iba1 expression by IHC in WT mice are 0.412 ±0.122, 0.625 ±0.135, 0.963 ±0.213 and 0.978 ±0.224.The data indica-ted that Iba1 expression increased in SAH KO group in comparison to SAH WT group on 1, 3, 5 day after SAH (P<0.05).Moreover, Nrf2 deficiency promoted the activation and polarization of M /M by increased Iba1 protein expression and CD16/32 +Iba1 +cells after SAH ( P<0.05). Conclusion SAH induces M/M activation and proliferation in mice, and Nrf2 deficiency promotes the activa-tion, proliferation and M1 polarization after SAH .

Objective To compare the clinical characters and hemodynamic data of the prone position and supine position percutaneous nephrolithotomy. Methods Patients with kidney stones in 100 cases were randomly assigned into the supine position group and prone position group.There were 50 cases in each group.The following data were recorded at preoperative,intraoperative,change position:the blood pressure,heart rate,respiration,saturation of blood oxygen and blood gas analysis results.The VAS score was recorded in patients for postural comfort,dyspnea and pain score. Results The systolic blood pressure in the preoperative,intraoperative,postoperative on supine position and prone position were as follows:(137±12),(119±15),(115±17) mm Hg and (137±10),(110±18),(104±16) mmHg.The diastalic blood pressure was as follows:( 81 ± 9 ),(74 ± 8 ),(63 ± 14 ) mm Hg and ( 84 ± 8 ),(63 ± 9 ),(60 ± 15) mm Hg.Compared with preoperative,there was a blood pressure decreased in both groups.The blood pH at preoperative,intraoperative,postoperative in supine position and prone position:7.4 ± 0,7.3 ± 0,7.3 ± 0 and 7.4 ± 0,7.3 ± 0,7.3 ± 0.The bass excess (BE) of two groups were:(2.1 ± 0.5),(-2.7 ±0.5),( -1.5 ±0.5) mmol/L and (3.2 ±0.5),(-3.8 ±0.5),(-2.5 ±0.5) mmol/L.Compared with preoperative data,the pH and BE declined in both groups.The prone position had more pronounced decrease in serum sodium,serum potassium; but with no significant difference.Supine group in postural comfort and breathing difficulties were 1.6 ± 0.4 and 7.1 4± 05,while prone group were 7.5 ± 0.2 and 1.4 ± 0.3.The supine position showed better in postural comfort and breathing difficulties with statistical significance. Conclusions Compared with the prone position,the supine positioned percutaneous nephrolithotomy could have less influence on hemodynamics,blood gas analysis.It could have better postural comfort.