Background and objective Radiation therapy is one of the most common treatments for non-small cell lung cancer(NSCLC).However,the insensitivity of some tumor cells to radiation is one of the major reasons for the poor efficacy of radiotherapy and the poor prognosis of patients,and exploring the underlying mechanisms behind radioresistance is the key to solving this clinical challenge.This study aimed to identify the molecules associated with radioresistance in lung ad-enocarcinoma(LUAD),identified thyroid hormone receptor interactor 13(TRIP13)as the main target initially,and explored whether TRIP 13 is related to radioresistance in LUAD and the specific mechanism,with the aim of providing theoretical basis and potential targets for the combination therapy of LUAD patients receiving radiotherapy in the clinic.Methods Three data-sets,GSE18842,GSE19188 and GSE33532,were selected from the Gene Expression Omnibus(GEO)database and screened for differentially expressed genes(|log FC|＞1.5,P＜0.05)in each of the three datasets using the R 4.1.3 software,and then Venn diagram was used to find out the differentially expressed genes common to the three datasets.The screened differential genes were then subjected to protein-protein interaction(PPI)analysis and module analysis with the help of STRING online tool and Cytoscape software,and survival prognosis analysis was performed for each gene with the help of Kaplan-Meier Plotter database,and the TRIP13 gene was identified as the main molecule for subsequent studies.Subsequently,the human LUAD cell line H292 was irradiated with multiple X-rays using a sub-lethal dose irradiation method to construct a radioresistant cell line,H292DR.The radioresistance of H292DR cells was verified using cell counting kit-8(CCK-8)assay and clone formation assay.The expression levels of TRIP 13 in H292 and H292DR cells were measured by Western blot.Small interfering RNA(siRNA)was used to silence the expression of TRIP 13 in H292DR cells and Western blot assay was performed.The clone formation ability and migration ability of H292DR cells were observed after TRIP13 silencing,followed by the detection of changes in the expression levels of proteins closely related to homologous recombination,such as ataxia telangiectasia mutated(ATM)protein.Results Screening of multiple GEO datasets,validation of external datasets and survival analysis revealed that TRIP 13 was highly expressed in LUAD and was associated with poor prognosis in LUAD patients who had received radiation therapy.And the results of gene set enrichment analysis(GSEA)of TRIP13 suggested that TRIP13 might be closely associated with LUAD radioresistance by promoting homologous recombination repair after radiation therapy.Experimentally,TRIP13 expression was found to be upregulated in H292DR,and silencing of TRIP13 was able to increase the sensitivity of H292DR cells to radiation.Conclusion TRIP13 is associated with poor prognosis in LUAD patients treated with radiation,possibly by promoting a homologous recombination repair pathway to mediate resistance of LUAD cells to radiation.

Objective:To discuss the effect of curcumin on the proliferation,migration,and invasion of the human prostate cancer C4-2 and LNCaP cells,and to clarify its possible mechanism.Methods:The lentiviral transfection system was used to transfect the C4-2 and LNCaP cells,regarded as shCD147-C4-2 group and shCD147-LNCaP group.RNA interference technology was used to prepare the CD147-silenced cells;the cells transfected with an empty vector were regarded as negative control and divided into shNC-C4-2 group(shNC-C4-2 cells)and shNC-LNCaP group(shNC-LNCaP cells).The C4-2 and LNCaP cells at logarithmic growth phase,as well as shCD147-C4-2 and shCD147-LNCaP cells,were treated with 20 μmol·L-1 curcumin.The morphology of the cells in various groups was observed under microscope at 0 and 24 h of treatment;MTT method was used to detect the proliferation activities of the cells in various groups;cell scratch assay was used to detect the migration rates of the cells in various groups;Western blotting method was used to detect the expression levels of apoptosis,invasion,and migration-related proteins in the cells in various groups.Results:Compared with C4-2 group,the expression of CD147 protein in the cells in shCD147-C4-2 group was significantly decreased after CD147 gene silenting.Compared with LNCaP group,the expression level of CD147 protein in the cells in shCD147-LNCaP group was significantly decreased after CD147 gene silenting.Compared with 0 h of treatment,some cells in C4-2 and LNCaP groups after 24 h of treatment with 20 μmol·L-1 curcumin,showed apoptosis signs with the presence of typical apoptotic bodies.The apoptotic phenomena in shCD147-C4-2 and shCD147-LNCaP groups was reduced.The MTT assay results showed that compared with C4-2+0 μmol·L-1 curcumin group,the proliferation activities of the cells in C4-2+20 μmol·L-1 curcumin group,C4-2+40 μmol·L-1 curcumin group,C4-2+60 μmol·L-1 curcumin group,and C4-2+80 μmol·L-1 curcumin group were decreased(P<0.01).Compared with LNCaP+0 μmol·L-1 curcumin group,the proliferation activity of the cells in LNCaP+20 μ mol·L-1 curcumin group,LNCaP+40 μmol·L-1 curcumin group,LNCaP+60 μmol·L-1 curcumin group,and LNCaP+80 μmol·L-1 curcumin group were decreased(P<0.01).Compared with shNC-C4-2 group,the proliferation activity of the cells in shNC-C4-2+20 μmol·L-1 curcumin group was decreased(P<0.01).Compared with shNC-C4-2+20 μmol·L-1 curcumin group,the proliferation activity of the cells in shCD147-C4-2+20 μmol·L-1 curcumin group was increased(P<0.01).Compared with shNC-LNCaP group,the proliferation activity of the cells in shNC-LNCaP+20 μmol·L-1 curcumin group was decreased(P<0.01);compared with shNC-LNCaP+20 μmol·L-1 curcumin group,the proliferation activity of the cells in shCD147-LNCaP+20 μmol·L-1 curcumin group was significantly increased(P<0.01).The cell scratch healing assay results showed that compared with C4-2 group,the migration rates of the cells in C4-2+20 μmol·L-1 curcumin group and C4-2+40 μmol·L-1 curcumin group after 24 h of treatment were decreased(P<0.01);compared with LNCaP group,the migration rates of the cells in LNCaP+20 μmol·L-1 curcumin group and LNCaP+40 μmol·L-1 curcumin group were increased(P<0.01);compared with shNC-C4-2 group,the migration rate of the cells in shNC-C4-2+20 μmol·L-1 curcumin group was decreased(P<0.01);compared with shNC-C4-2+20 μmol·L-1 curcumin group,the migration rate of the cells in shCD147-C4-2+20 μmol·L-1 curcumin group was significantly increased(P<0.05);compared with shNC-LNCaP group,the migration rate of the cells in shNC-LNCaP+20 μmol·L-1 curcumin group was decreased(P<0.01);compared with shNC-LNCaP+20 μmol·L-1 curcumin group,the garation rate of the cells in shCD147-LNCaP+20 μmol·L-1 curcumin group was significantly increased(P<0.05).The Western blotting results showed that compared with C4-2 group,the expression levels of Bcl-2-associated X protein(Bax),cleaved Caspase-3,and poly ADP-ribose polymerase 1(PARP1)proteins in the cells in C4-2+20 μmol·L-1 curcumin group and C4-2+40 μmol·L-1 curcumin group were significantly increased(P<0.01),and the expression levels of Bcl-2 protein was significantly decreased(P<0.05 or P<0.01);compared with LNCaP group,the expression levels of Bax,cleaved Caspase-3,and PARP1 proteins in the cells in LNCaP+20 μmol·L-1 curcumin group and LNCaP+40 μmol·L-1 curcumin group were significantly increased(P<0.01),and the expression level of Bcl-2 protein in the cells in LNCaP+40 μmol·L-1 curcumin group was decreased(P<0.01);compared with shNC-C4-2 group,the expression levels of Bax,cleaved Caspase-3,and PARP1 proteins in the cells in shNC-C4-2+20 μmol·L-1 curcumin group were significantly increased(P<0.05 or P<0.01),and the expression level of Bcl-2 protein was significantly decreased(P<0.05);compared with shNC-C4-2+20 μmol·L-1 curcumin group,the expression levels of Bax and cleaved Caspase-3 proteins in the cells in shCD147-C4-2+20 μmol·L-1 curcumin group were significantly decreased(P<0.01);compared with shNC-LNCaP group,the expression levels of Bax,cleaved Caspase-3,and PARP1 proteins in the cells in shNC-LNCaP+20 μmol·L-1 curcumin group were significantly increased(P<0.05 or P<0.01),and the expression level of Bcl-2 protein was significantly decreased(P<0.05);compared with shNC-LNCaP+20 μmol·L-1 curcumin group,the expression levels of Bax,cleaved Caspase-3,and PARP1 proteins in the cells in shCD147-LNCaP+20 μmol·L-1 curcumin group were significantly decreased(P<0.05 or P<0.01),and the expression level of Bcl-2 protein was significantly increased(P<0.05).Compared with C4-2 group,the expression levels of E-cadherin protein in the cells in C4-2+20 μmol·L-1 curcumin group and C4-2+40 μ mol·L-1 curcumin group were significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly decreased(P<0.01);compared with LNCaP group,the expression levels of E-cadherin protein in the cells in LNCaP+20 μmol·L-1 curcumin group and LNCaP+40 μmol·L-1 curcumin group were significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins in the cells in LNCaP+40 μmol·L-1 curcumin group were significantly decreased(P<0.01);compared with shNC-C4-2 group,the expression levels of N-cadherin and Vimentin proteins in the cells in shNC-C4-2+20 μmol·L-1 curcumin group were significantly decreased(P<0.01);compared with shNC-C4-2+20 μmol·L-1 curcumin group,the expression level of E-cadherin protein in the cells in shCD147-C4-2+20 μmol·L-1 curcumin group was significantly decreased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly increased(P<0.01);compared with shNC-LNCaP group,the expression level of E-cadherin protein in the cells in shNC-LNCaP+20 μmol·L-1 curcumin group was significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly decreased(P<0.01);compared with shNC-LNCaP+20 μmol·L-1 curcumin group,the expression level of E-cadherin protein in the cells in shCD147-LNCaP+20 μmol·L-1 curcumin group was significantly decreased(P<0.01),and the expression level of N-cadherin was significantly increased(P<0.05).Conclusion:Curcumin inhibits the proliferation,migration,and invasion of the prostate cancer cells in vitro and induces the apoptosis;silencing the CD147 gene partially reduces its inhibitory effect and its ability to induce the apoptosis.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

An auxiliary dining robot is designed in this paper, which implements the humanoid feeding function with theory of inventive problem solving (TRIZ) theory and aims at the demand of special auxiliary nursing equipment. Firstly, this robot simulated the motion function of human arm by using the tandem joints of the manipulator. The end-effector used a motor-driven spoon to simulate the feeding actions of human hand. Meanwhile, the eye in hand installation style was adopted to instead the human vision to realize its automatic feeding action. Moreover, the feeding and drinking actions of the dining robot were considered comprehensively with the flexibility of spatial movement under the lowest degree of freedom (DOF) configuration. The structure of the dining robot was confirmed by analyzing its stresses and discussing the specific application scenarios under this condition. Finally, the simulation results demonstrate high-flexibility of the dining robot in the workspace with lowest DOF configuration.
Computer Simulation ; Equipment Design ; Hand ; Humans ; Movement ; Robotics/methods*

Objective ToassessthevalueofGdGEOBGDTPAenhancedT1ρimaginginevaluatingtheseverityandinflammation gradeinnonalcoholicsteatohepatitis(NASH)rabbitsmodel.Methods NASH modelswereestablishedin26adultrabbitsbyfeeding withthehighGfat,highGcholesteroldietinavarieddurations (0,4,8,12 weeks).T1ρ,T1ρinthehepatobiliaryphase (HBP)and changeofT1ρ(Δ%)werecomparedamongthedifferentgroupswhichweredeterminedbydifferentnonGalcoholicfattyliverdisease activityscore(NAS)andinflammationgrades.SpearmancorrelationanalysiswasusedtoassessthecorrelationsofT1ρ,T1ρ(HBP) withNASscoresandinflammationgrades.ROCcurvewasperformedtoevaluatethediagnosticvalueofT1ρ,T1ρ(HBP)inpredicting NASHandadvancedinflammation.Results T1ρandT1ρ(HBP)werepositivelyassociatedwithNASandinflammationscores.The differencesofT1ρ(HBP)amongNASH,nonalcoholicfattyliver(NAFL)andnormalliverwerestatisticallysignificant(P＜0.05). T1ρ(HBP)wassignificantlydifferentintherabbitswithgrade3inflammationfromintherabbitswithgrade0,grade1andgrade2 inflammation (P＜0.05).AUCsofT1ρandT1ρ(HBP)fordifferentiatingNASH were0.849and0.949,respectively.AUCofT1ρand T1ρGHBPfordiagnosinggrade2andgrade3inflammationwere0.925and0.922,respectively.Fibrosisandinflammationwerethe mainindependentfactorsaffectingT1(HBP).Conclusion GdGEOBGDTPAenhancedT1ρimagingcanreflecttheseverityofNASH anddegreeofinflammation.T1ρ(HBP)mightbeamoresuperiornoninvasiveimagingbiomarkerthannonGenhancedT1ρforassessmentof NASHactivityandinflammationgrading.

Objective To explore the predictive value of CT image texture analysis for early enlargement of hypertensive intracerebral hemorrhage.Methods One hundred and eight patients with hypertensive intracerebral hemorrhage were divided into enlarged hematoma group (positive group)and non-enlarged hematoma group (negative group),according to whether the volume of hematoma on 24 h follow up CT scan was more than 30% or 6 mL of the baseline CT.Phillis Radiomics Tool V93 software was used to segment the hematoma on CT plain scan images of two groups,four features of first-order and three of gray-level co-occurrence matrix (GLCM),thirteen of gray-level size zone matricx (GLSZM)and eleven of gray-level run-length matricx (GLRLM)were obtained.The differences of thirty-one texture features between the two groups were compared.The ROC curves of the features with statistical differences were analyzed.The independent predictors of early enlargement of intracerebral hemorrhage were screened by Logistic multivariate regression model.Results Among the one hundred and eight patients,twenty-eight were positive group and eighty were negative group.Skewness and long run low gray-level emphasis (LRLGE)in positive group were significantly higher than those in negative group (P＜0.05).There was no significant difference in the remaining twenty-nine features between the two groups (P＞0.05).ROC curve analysis showed that the AUC of Skewness,LRLGE and their combined diagnosis were 0.634,0.814 and 0.828,respectively.The independent variables were screened by stepwise regression analysis.The LRLGE (OR＝1.238,95%CI＝1.009－1.51 9,P＜0.05)was selected as the regression model, suggesting that LRLGE was an independent predictor of the early enlargement of intracerebral hemorrhage.Conclusion Texture analysis of CT images is helpful to predict the early enlargement of hypertensive intracerebral hemorrhage,and LRLGE based on GLRLM algorithm can be used as an independent predictor.

AIM:To investigate the effect of quercetin on the biological functions of rat bone marrow-derived endothelial progenitor cells (EPCs) and its potential mechanisms.METHODS:The bone marrow-derived mononuclear cells of Sprague-Dawley rats were isolated by density gradient centrifugation.The differentiated EPCs were cultured specially and stained with DiI-Ac-LDL and FITC-UEA-1.CD133+ and FLK-1+ were detected on the cell surfaces.After 14 d, the EPCs were incubated with a PI3K inhibitor BYL719 (3 μmol/L) and an ERK inhibitor FR180204 (15 μmol/L).After incubation of the inhibitors for 2 h, the cells were treated with quercetin at different concentrations (0, 10, 20, 40, 80 and 100 μmol/L).MTT assay and Transwell assay were used to detect cell viability and the number of migratory cells.The protein levels of AKT, eNOS, ERK and their phosphorylated status were determined by Western blot.RESULTS:Quercetin enhanced the viability and migration of the EPCs at a dose-dependent manner.However, the PI3K inhibitor BYL719 suppressed the QUE-induced cell viability and migration.Moreover, ERK inhibitor FR180204 exerted the similar inhibitory effect on the cell viability but had no effect on cell migration.Quercetin activated the phosphorylation of AKT, eNOS and ERK.On the other hand, BYL719 was observed to inhibit the phosphorylation of AKT and ERK.FR180204, however, was showed to inhibit the phosphorylation of ERK only.On the contrast, the stimulatory effects that quercetin exerted on the expression of eNOS and its phosphorylation were suppressed by BYL719 and FR180204.CONCLUSION:Quercetin stimulates the viability and migration of EPCs via PI3K/AKT/eNOS and ERK/eNOS signaling pathway, which would be beneficial for cardiovascular health.

Objective To study the thalamic metabolic alterations and its correlation with cognitive impairment in patients with cerebral small vessel disease(CSVD).Methods The cognitive function of 34 patients with CSVD and 26 matched volunteers were evaluated by Montreal cognitive assessment(MoCA), and received single voxel 1H-MRS examination to detect the content of NAA,Cho and Cr,and record the ratio of NAA/Cr and Cho/Cr on bilateral thalami.The differences of NAA/Cr, Cho/Cr on bilateral thalami between the two groups were compared, and the correlation between NAA/Cr,Cho/Cr and MoCA total score and its sub-items score in CSVD group were analyzed.Results ①The MoCA of total score as well as its sub-items such as visual space and executive ability,memory,attention and language for CSVD group were significantly lower than that for the control group(P<0.05);②NAA/Cr on bilateral thalami in CSVD group were both lower than that in the control group(left 1.57±0.18,1.68±0.17,t=2.46,P=0.02;right 1.66±0.21,1.78±0.19,t=2.23,P=0.03), the differences were statistically significant (P<0.05);there were no significantly differences in the ratio of Cho/Cr between the two groups(P>0.05);③In CSVD group, the ratio of NAA/Cr on both bilateral thalami were significantly positively correlated with MoCA score (left r=0.83,right r=0.79,P<0.05)as well as visual space and executive ability(left r=0.65,right r=0.46,P<0.05), memory(left r=0.59, right r=0.50, P<0.05), attention(left r=0.42, right r=0.52, P<0.05),language(left r=0.52, right r=0.41, P<0.05), abstraction(left r=0.47, right r=0.40, P<0.05), orientation(left r=0.48,right r=0.42, P<0.05),Cho/Cr were not significantly correlated with MoCA total score and its sub-items(P>0.05).Conclusion The thalamic neuron has been damaged and dysfunctioned in patients with CSVD,and this metabolic abnormality may be related to a wide range of cognitive impairment in CSVD patients.

Objective To examine the reliability and validity of the Chinese version of the metacognition assessment scale 2009 (MAS-R 2009).Methods Sixty college students from a medical university in Shenyang were enrolled in the study.All the subjects were required to fill in the basic information questionnaire,IRI-C,SPM,and the Chinese version of the MAS-R 2009 and had to be interviewed.Two to four weeks later,6 college students were randomly selected to be interviewed again.Results Cronbach'sα coefficient of the Chinese version of MAS-R 2009 was 0.934,test-retest reliability of the scale was 0.935 (r ＜ 0.01),and inter-rater reliability of the scale was 0.832 (P ＜ 0.01).The Chinese version of the MAS-R 2009 had good content validity.The correlation coefficient between the items and the subscales in MAS-R 2009 showed high correlation,and the correlation coefficient ranged from 0.456 to 0.905.Conclusion The results indicate that the reliability and validity of the Chinese version of the revised metacognitive assessment scale 2009 has satisfied the psychometric requirements.It has a certain application value for domestic research and scientific research on the ability of mentalization.

Alleles ; Crystallography, X-Ray ; HIV Infections ; HIV-1 ; HLA-B Antigens ; chemistry ; immunology ; Humans