Abstract:Objective：To prepare gene loaded nanaobubbles and explore their effects of ultrasonography and targeted killing of hepatocellular carcinoma cells in vivo and in vitro. Methods：Positively charged nanobubbles with the peripheml phospholipid shells filled by suphurhexafluoride（SF6）gas were fabricated through the method of lipid thin-film，hydration and mechanical agitations. Then simplex herpes virus thymidine kinase（HSV-TK）plasmid DNA coupled with alpha fetoprotein（AFP）promoter was conjugated to create gene loaded nanobubbles. The characteristics such as morphology，average particle size，zeta potential，capacity of DNA binding and gene transfection were detected. Then the effect of ultrasound contrast enhancement imaging was investigated in vivo and in vitro. Finally，the killing efficiency of gene-loaded nanobubbles on BEL-7402 and SMCC-7721 cells when combined with ultrasound-targeted microbubble destruction（UTMD）was detected using CCK-8 and flow cytometry（FCM）assay. Results：The nanobubbles appeared as a spherical morphology with a core-shell structure under TEM，and they were about 667 nm in mean hydrodynamic diameter with positive charge. Nanobubbles can effectively bind with plasmid DNA when particle/DNA weight ratio was set at 5∶1. The gene-loaded nanobubbles had good ultrasonic contrast enhancement characteristics in vitro and in vivo ultrasonography. RT-PCR assays indicated that nanobubbles combined with UTMD enabled HSV-TK to be expressed in AFP positive hepatocellular carcinoma cells rather than AFP negative ones. The analysis of CCK-8 and FCM showed that gene-loaded nanobubbles combined with UTMD could significantly inhibit the proliferation of BEL-7402 cells and induce apoptosis，which was significantly different from other groups（P < 0.05）. Conclusion：Gene-loaded nanobubbles with good ultrasonic imaging function can effectively induce targeted killing of AFP positive hepatocellular carcinoma cells.

Abstract:Objective：To investigate the expression of lncRNA BANCR in gastric cancer（GC），and explore the potential biological function and underlying molecular mechanism on cell migration and invasion. Methods：The mRNA expression level of BANCR in GC tissues was detected by quantitative real-time PCR（QPCR）. MKN28 cells was transfected with siRNA against BANCR. Transwell assays was used to detect the ability of cell migration and invasion and QPCR was used to detect the expression of metastasis-related markers. Results：The expression level of BANCR in GC tissues was significantly higher than that in adjacent tissues，which consistent with TCGA data. Down-regulation of BANCR repressed GC cell migration and invasion. Furthermore，the expression level of CDH1 was up-regulated，and the expression level of Vimentin and ZEB1 was down-regulated in BANCR knocking-down cells. Interesting，the expression level of ZEB1 was restored by decreasing miR-203 in BANCR knocking-down cells. Conclusion：BANCR was over-expressed in GC tissues and play an oncogenic role by regulating the miR-203-ZEB1-CDH1 axis in GC.

Abstract:Objective：To observe the effect of 2，3，4’，5-tetrahydroxystilbene-2-O-β-D-glucoside （TSG） on hyperlipidemic fatty liver in rats，and explore the potential mechanisms by PPAR α signaling pathway. Methods：SD rats were randomly divided into control group，model group，TSG 80 mg/kg group，MK886 plus TSG 80 mg/kg group. The rat model was established by orally feeding high-fat emulsion for 4 weeks. Then TSG was administered to these rats for 6 weeks. TC，TG and FFA levels in serum and hepatic tissues，hepatic weight coefficient，the levels of alanine aminotransferase（ALT）and aspartate aminotransferase（AST）in serum were measured；and the hepatic histopathological changes were observed. Meanwhile，the expressions of PPAR α，LC3Ⅰ，LC3Ⅱ，Beclin 1 and p62 proteins in hepatic tissues were measured by Western blot. Results：Compared with the model group，TSG could significantly decrease TC，TG and FFA levels in serum，TG and FFA contents in hepatic tissues，hepatic weight coefficient，and also the serum levels of ALT and AST（P＜0.05 or P＜0.01）. Meanwhile，the histological evaluation of liver specimens revealed that lipid accumulation in TSG-treated group was obviously ameliorated. Western blot results showed that TSG could markedly up-regulated the expressions of hepatic PPAR α，LC3Ⅱ，Beclin 1 proteins，and down-regulated the expression of p62（P＜0.05 or P＜0.01）. However，the effect of TSG was weakened or cancelled when pretreatment with PPAR α antagonist MK886. Conclusion：TSG was effective in treating hyperlipidemic fatty liver in rats，and its mechanism might be related to the up-regulation of LC3Ⅱ and Beclin 1 protein expressions，down-regulation of p62 protein expression to activate autophagy by activation of PPAR α，and eventually to improve lipid metabolism.

Abstract:Objective：To explore anti-cancer activities of a novel bis-aryl urea compound（code name：N69B）using non-small cell lung cancer A549 cells. Methods：The non-small cell lung cancer A549 cells were choosed and treated by N69B at different concentrations. The cell proliferation was quantified by CCK-8 method；the cell cycle was determined by flow cytometry；the apoptosis rate were detected by Annexin V/PI double staining；and the relative expression of Cleaved caspase-3，8，9 was measured by the Western blot. Results：Compared with the DMSO control group，N69B inhibited the proliferation of A549 cells in manners that are time-and dose-dependent（P < 0.05 or P < 0.01）. Twenty-four hours after the treatment with N69B at 0.5，1.0 and 1.5 μM，respectively，the number of cells in G2 phase significantly increased（P < 0.01）；the apoptosis rate increased in different degrees；Cleaved caspase-3，8，9 expression showed a dose-dependent elevation. Conclusion：N69B inhibits the proliferation of A549 cells，possibly through cell cycle arrest in G2-M phase and apoptosis induced by caspase activation.

Abstract:Objective：To explore the impact of wogonin on the proliferation and apoptosis of medulloblastoma cell line DAOY.Methods：DAOY cells were divided into experimental groups（added with wogonin at difference concentrations）and control group. The proliferation of DAOY was detected using CCK-8 assay kit．The apoptosis was analyzed by Annexin Ⅴ-FITC/PI double staining and the activity of caspase-3 was determined via colorimetry. Moreover，we also detected the tumor inhibiting function of wogonin in vivo using subcutaneous tumor model. Results：Wognin remarkably inhibited the proliferation of medulloblastoma cell DAOY and induced the apoptosis in a dose and time dependent manner. The apoptosis was characterized by the increase of apoptosis protein caspase-3. Conclusion：Wogonin could inhibit medulloblastoma cell proliferation both in vitro and in vivo via inducing medulloblastoma cells apoptosis.

Abstract:Objective：To explore the expression and significance of FOXO1 in mature B-cell neoplasms. Methods：The expression of FOXO1 in mature B-cell neoplasms was mined in Oncomine database. The different expressions of FOXO1 between the normal tissue and B-cell neoplasms were analyzed by BIOGPS database. The survival time of patients with mature B-cell neoplasms was detected by GEPIA. The FOXO1 interacting proteins were analyzed by String-DB database. Results：At the mRNA level，FOXO1 was lower in mature B-cell neoplasms than in normal tissue，and the expression level was not notable correlated with the prognosis of mature B-cell neoplasms（Logrank P=0.39）. FOXO1 related proteins are EP300、JUN、MYC、STAT1、FOS、SPI1、E2F，etc. Conclusion：The information of FOXO1 expression in mature B-cell neoplasms could be quickly extracted by using data mining and would be an scientific and theoretical support for the further research.

Abstract:Objective：To discover unknown LncRNAs associated with Coronary Artery Disease（CAD）in peripheral blood. Methods：Three pairs of clinical CAD group and control blood plasma samples were texted in this experiment by high-throughput sequencing methods. Cuffdiff software was used to get the expression profiles of LncRNAs，differentially expressed LncRNAs were identified based on fold change and p-value. Differently expressed genes in peripheral plasma and blood monocytes were verified by Q-PCR in 36 pairs of clinical CAD group and controls. Results：The optimal 45 up-regulated and 29 down-regulated LncRNAs were detected. Three LncRNAs uc003pxg.1，ENST00000565257，ENST00000568324 were up-regulated obviously in peripheral blood mononuclear cells of CAD patients. Area under the ROC curve results of uc003pxg.1，ENST00000565257，ENST00000568324 were 0.812 5，0.742 4，0.742 4 respectively. These genes were all up-regulated in CAD patients obviously and these outcomes were consistent with the sequencing results. Conclusion：The ideal LncRNAs were detected preliminarily. This founding lays the foundation for further research，and provides theoretical basis of LncRNA using for CAD early clinical screening.

Abstract:Objective：To investigate the clinical efficacy of epidermal growth factor receptor（EGFR）mutated tyrosine kinase inhibitor（TKI）combination of pemetrexed and carboplatin versus chemotherapy alone after first-line EGFR-TKI resistance in advanced lung adenocarcinoma. Methods：Fifty patients with stage ⅢB~Ⅳ lung adenocarcinoma that had been treated with EGFR-TKI were divided into two groups：the combined group was treated with pemetrexed+carboplatin+gefitinib or icotinib. the other was chemotherapy alone. The therapeutic effect and side effects of the two groups were observed. Results：There was no significant difference in DCR and ORR between the combined group and chemotherapy group，and the mPFS of the two groups were 10.4 months vs 8.9 months（P > 0.05）；The mPFS of patients with T790M-negative were 11.1 months vs 8.3 months，and 7.6 months vs 5.7 months in patients with brain metastasis，which showed a better outcome in combined group（P < 0.05）；In the subgroups of smoking and different mutation types of EGFR，there was no significant difference in the curative efficacies between the two treatments. The main side effects of the two groups were myelosuppression、digestive tract reaction and fatigue. Skin rash and diarrhea in grade Ⅰ~Ⅱ were significantly higher in combined group（P < 0.05）. Conclusion：The combination treatment of continuation first-line EGFR-TKI plus pemetrexed and carboplatin in advanced lung adenocarcinoma has certain clinical promotion and application value.

Abstract:Objective：Serum ischemia-modified albumin（IMA）is a newly inflammatory marker associated with oxidative stress，and the levels of serum IMA in chronic obstructive pulmonary disease（COPD）patients were researched in this study. Methods：A total of 156 patients were retrospectively enrolled in this study，including 45 patients with stable COPD and 111 patients with acute exacerbation of COPD（AECOPD），in which 53 patients without respiratory failure and 58 patients with respiratory failure. A total of 114 healthy participants were recruited to the control group. The levels of IMA，neutrophil to lymphocyte ratio（NLR），C-reactive protein（CRP）and pulse oxygen saturation（SpO2）were detected. Results：Compared with the control group，the levels of IMA in stable COPD group and AECOPD group were higher，especially in AECOPD patients（P < 0.05，respectively）. The levels of IMA in AECOPD patients with respiratory failure were significantly higher than that in AECOPD patients without respiratory failure（P < 0.05）. The levels of IMA show positive correlation with NLR and CRP in COPD patients（r=0.228，0.385，all P < 0.05）. Conclusion：Our study indicated that the levels of IMA in COPD patients were significantly higher than those in healthy participants，especially in patients with AECOPD. IMA may be a potential biomarker for evaluating the inflammatory response in COPD patients.

Abstract:Objective：The aim of the present study was to evaluate the relationship of lipoprotein-associated phospholipase A2（Lp-PLA2）with the severity and prognosis of non-ST-elevation acute coronary syndromes（NSTE-ACS）. Methods：We conducted a hospital-based study to examine the potential association of Lp-PLA2 with the severity and prognosis of NSTE-ACS. A total of 157 unrelated subjects（46 UAP patients，49 Non-STEMI patients and 62 non-CAD subjects as control）who underwent elective coronary angiography from January 2014 to May 2015 admitted to Department of Cardiology，the Affiliated Jiangning Hospital of NMU. Results：We observed that the plasma levels of Lp-PLA2 were significantly higher among non-ACS patients compared to non-CAD subjects，moreover，its level is most high in Non-STEMI patients. There was also a highly remarkable association of Lp-PLA2 with double-vessel and triple-vessel disease when patients were divided into subgroups based on the number of diseased vessels. After 1-year follow up，we found that Lp-PLA2 levels were also related to events of MACE with statistical significance. Conclusion：Our results suggest that Lp-PLA2 is associated with the severity and prognosis of NSTE-ACS.

Abstract:Objective：To quantitatively evaluate nerve roots by measuring fractional anisotropy（FA） values in lumbar intervertebral disc related compression of lumbosacral plexus nerve roots by MR diffusion tensor imaging（DTI）. To evaluate the potential value of DTI in preoperative diagnosis and prognosis evaluation of disc related lumbosacral nerve roots compression. Methods：Thirty-four unilateral disc related lumbosacral nerve roots compression patients underwent MR imaging using diffusion tensor tractography（DTT）. FA values for nerve roots were calculated at three levels from DTI images. Japanese Orthopedic Associationfor the Assessment of Treatment for Low Back Pain（JOA）score and correlation analysis were performed on the clinical function of the patients. Results：The abnormalities of symptomatic nerve tracts were distinctly showed by tractography. On the symptomatic side of nerve roots，the mean FA values displayed a significant declining tendency from proximal to distal. The FA values of the symptomatic side of the nerve roots were significantly lower than those of the asymptomatic side at the proximal，medial and distal levels. The mean FA value of nerve roots correlated moderately with the JOA score. Conclusion：DTI imaging of the lumbosacral plexus nerve roots in lumbosacral nerve roots compression is related to the preoperative evaluation of responsible nerve roots compression of lumbar disc nerve roots. The diversities of nerve roots quantitative FA values reflect the degenerated nerve roots caused by the abnormal sensation and motion dysfunction.

Abstract:Objective：To investigate the viscoelastic mechanical behavior of human periodontal ligament（PDL），obtain relevant data through creep test，construct a three-parameter viscoelastic constitutive model and obtain model parameters. Methods：Four human bone-PDL-tooth complex was cut to make the transverse samples. A dynamic thermomechanical analyzer was used to perform creep tests，and time-dependent test data were obtained. The three-parameter Zener model was constructed based on continuous medium mechanics，and the experimental data were fitted to obtain the specific characteristic parameters of the model. Results：The curves of the four samples were consistent，the correction coefficients are all above 0.95，the highest fitting sample is 0.986 54，and the residual sum of squares are all small. Conclusion：It is proved that the Zener model can be used to describe the creep characteristics in the viscoelastic mechanical behavior of human PDL.

Abstract:Objective：To evaluate the difference of periapical bone defect morphology caused by apical periodontitis（AP）and vertical root fracture（VRF）. Methods：Cone-beam computed tomography（CBCT）data of the maxillary and mandibular posterior teeth with AP and VRF and peripheral periapical defects were selected and reconstructed by Mimics software and quantitatively analyzed in the defect area. The percentage of bone defect volume above the level of the apical foramen of the two groups was calculated as the volume of the total bone defect. Results：The volume ratio between the two groups was statistically significant（P < 0.05）. When the volume ratio tends to 1，the possibility of vertical root fracture is great. Conclusion：VRF-induced periapical bone defect is mainly located above the level of the apical foramen of the tooth. Quantitative measurement of the periapical bone defect contributes to the diagnosis of VRF.

Abstract:Objective：By integrating the clinical information group，genome and transcriptome of lung adenocarcinoma，a prognostic risk prediction model was constructed to provide evidence of lung adenocarcinoma patients. Methods：The data of 522 patients with lung adenocarcinoma were downloaded from TCGA website，and the multi group database of lung adenocarcinoma was completed.Cox proportional hazard model was used to evaluate the effect of multigroup data on the prognosis of LUAD. A prognostic risk prediction model based on clinical information，genotyping and multigroup information of gene expression was constructed. ROC curves and AUC was used to assess the ability of risk recognition in prognostic models. Results：A total of 386 patients with lung adenocarcinoma were included in the multi group database. One clinical information group，five genomes and four transcription groups for prognostic factors were detected to associate with the prognosis of lung adenocarcinoma.HR（95%CI）of prognosis of lung adenocarcinoma for high-risk group was 3.67（95% CI=2.46~5.49），as compared with low-risk group. After combining genome，transcriptome and clinical information，the ROC curve is 0.694（95%CI=0.633~0.754）. Conclusion：Prognostic risk prediction index combining clinical information group，genome and transcriptome features can effectively distinguish the prognosis of lung adenocarcinoma patients. The results will provide effective support for accurate treatment of lung adenocarcinoma patients.