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CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.
Subject(s)
Humans , Antineoplastic Agents/therapeutic use , Apoptosis , Bortezomib/pharmacology , Cell Line, Tumor , Cell Proliferation , ErbB Receptors/antagonists & inhibitors , G2 Phase Cell Cycle Checkpoints , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , M Cells , Multiple Myeloma/drug therapyABSTRACT
Objective:To establish and verify the prediction model of benign or malignant of solitary pulmonary nodules (SPNs≤20 mm) based on artificial intelligence.Methods:Totally 338 SPNs (≤20 mm) from 279 patients, confirmed by operation and pathology, were selected in Zhongshan Hospital Xiamen University from November 2018 to May 2020. Clinical data (age, gender, smoking history, individual and family history of malignancy), image features (maximum diameter, minimum diameter, solid proportion, volume, lobulation sign, burr sign, vacuole sign, cavity sign, pleural indentation sign, and radiomic features (maximum CT value, minimum CT value, average CT value, median CT value, CT value standard deviation, skewness, peak, energy, entropy) were analyzed retrospectively. All the data of patients were randomly divided into training set (271 SPNs) and test set (67 SPNs). In the training set, the clinical, image features and radiomic features were first selected by the least absolute shrinkage and selection operator (LASSO) regression, then the independent risk factors of SPN (≤20 mm) were screened out by multi-variate logistic regression analysis, and the nomogram prediction models were constructed. Finally, the data of test set were used to verify the prediction model by the ROC curve and calibration curve (CC).Results:In the training set of 271 SPNs, 81 SPNs were benign and 190 malignant. After analysis of LASSO regression and multi-factor logistics regression, the independent predictors of benign or malignant SPN were age, gender, largest diameter, vacuole sign and solid proportion. The prediction model was P=e x/(1+e x), x=-2.583+0.027×age+1.519×gender+0.127×maximum diameter-2.132×solid proportion+1.720×vacuole sign. The results of the model showed that the area under curve (AUC) of ROC was 0.850, and the sensitivity was 73.7%, specificity was 82.7% and accuracy was 82.3%. In the test set of 67 SPNs, 22 SPNs were benign and 45 malignant. The results showed that the AUC of ROC was 0.882, and the sensitivity was 82.2%, specificity was 81.8% and accuracy was 85.1%. The calibration nomogram of prediction model showed that CC from training set or test set well coincided with its individual ideal curve ( Ptraining=0.688, Ptest=0.618). Conclusion:Prediction model of benign or malignant SPN ≤20 mm is established based on AI; it can obtain the prediction probability and has good diagnostic efficiency.
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Objective To establish a long-term survival model of deep hypothermic circulatory arrest (DHCA) in rats,which could contribute to the research of organ damage mechanism and clinical treatments related to DHCA.Methods Twenty Sprague-Dawley rats were randomly (random number) divided into the sham group (n=10) and DHCA group (n=10).After anesthesia,a 20 G catheter was cannulated in the tail artery for arterial inflow,a multiorificed catheter in the right jugular vein for venous drainage,and a 24G catheter in the branch of left femoral artery for artery blood pressure monitoring.Rats in the DHCA group underwent DHCA procedure for 40 min after brain temperature cooled to 18℃,then rewarmed for 40 min,till the brain temperature were above 34℃.Rats in the sham group were cannulated but did not undergo cardiopulmonary bypass (CPB).Hemodynamic parameters and blood gas analysis were measured for 5 times (pre-CPB,15 min after CPB,10 min after rewarming,40 min after rewarming,and 30 min after CPB).Results One rat in the DHCA group died,and the rest rats survived.The lactate level in the DHCA group after rewarming during operation was significantly higher than that in the sham group (7.84 mmol/L vs 1.93 mmol/L,P＜0.05).Conclusions In this study,40-min DHCA model in rats is characterized by safe and long-term survival.
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The purified 3C8 was obtained by two step column purification,including Protein G affinity purification and DEAE anion exchange purification.The purity of purified 3C8 was about 93％ when analyzed by reverse column.SDS-PAGE showed that the purity of 3C8 was increased greatly by two step purification.By flowcytometry we found that 3C8 specifically binded with B7-H4/293T cells and did not bind with Mock/293T cells,moreover 3C8 did not bind with other B7 family members transgene cells.In confocal experiment 3C8 could specifically stained B7-H4/293T cells.In Western blot only B7-H4/293T cells showed positive band while Mock/293T cells showed negative result.The result of immunohistochemistry showed that B7-H4 was highly expressed in prostate cancer and renal cell carcinoma,while para-cancer tissues did not express B7-H4.The T cell proliferation experiment showed that B7-H4-Ig could bind to activate T cells and inhibit T cell proliferation,while 3C8 could block the binding of B7-H4-Ig and reverse the T cell proliferation inhibition effect of B7-H4-Ig by CFSE and CCK8 assay.The cytokine IFN-γ and IL-2 secreted by activating T cells was decreased by B7-H4-Ig and 3C8 could reverse the effect of B7-H4-Ig.
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Objective:To explore the impact of clinical nurses ' humanistic care knowledge reserve on their hu-manistic care ability .Methods:With the method of convenience sampling , a questionnaire survey was conducted among 1200 clinical nurses in post in 8 three grade hospitals in Shaanxi province .We analyzed the correlation be-tween nurses ' humanistic knowledge reserve and humanistic careability and sifted the independent influencing fac -tors of nursing humanistic care ability .Results:The total score of humanistic care ability was negatively associated with the four variables(P<0.05), such as thinking of the influence of humanistic care on their career development and so on, and was positively associated with other two variables (P<0.05), such as the main source of humanis-tic knowledge .Among them , four factors , such as thinking of the influence of humanistic care on their career de-velopment , the main source of humanistic knowledge and so on , were the independent influencing factors of nur-ses' humanistic care knowledge reserve .Conclusion: Nursing schools and hospitals should improve nurse ' s hu-manistic care ability by establishing the nursing concept of humanistic care , adding humanistic care courses , strengthening humanistic care education and carrying out humanistic care training and continuing education .
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Objective:To explore the impact of clinical nurses ' humanistic care knowledge reserve on their hu-manistic care ability .Methods:With the method of convenience sampling , a questionnaire survey was conducted among 1200 clinical nurses in post in 8 three grade hospitals in Shaanxi province .We analyzed the correlation be-tween nurses ' humanistic knowledge reserve and humanistic careability and sifted the independent influencing fac -tors of nursing humanistic care ability .Results:The total score of humanistic care ability was negatively associated with the four variables(P<0.05), such as thinking of the influence of humanistic care on their career development and so on, and was positively associated with other two variables (P<0.05), such as the main source of humanis-tic knowledge .Among them , four factors , such as thinking of the influence of humanistic care on their career de-velopment , the main source of humanistic knowledge and so on , were the independent influencing factors of nur-ses' humanistic care knowledge reserve .Conclusion: Nursing schools and hospitals should improve nurse ' s hu-manistic care ability by establishing the nursing concept of humanistic care , adding humanistic care courses , strengthening humanistic care education and carrying out humanistic care training and continuing education .
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Objective To study the value of magnetic resonance vessel wall imaging in assessing the atherosclerotic plaque burden of rabbit model.Methods We built up abdominal atherosclerotic animal model in 30 New Zealand rabbits by high lipid diet combined with abdominal artery denudation.The animals were divided into 3 groups randomly,which were the 1-week group,1-month group and 2-months group.The MRI and histology examination were carried out at relative time points.The correlations of area or thickness of vessel wall by MRI with histology examination were analyzed.Results Among the 30 rabbits,3 died due to anesthesia or surgery,one rabbit model failed because of the thin vessel,and another 3 died of diarrhea or inflammation during the high lipid diet feeding.Eventually,totally 23 rabbits fulfilled the examinations (7 in 1-week group,7 in 1-month group and 9 in 2-months group).The vessel wall area of histology examination grew larger along with the post-surgery duration,from 1.7663 mm2of 1-week group to 2.4371 mm2 of the 1-month group till 3.5978 mm2 of 2-months group,with statistic significant difference among 3 groups (F=5.052,P=0.017).There were strong correlations of area or thickness vessel wall resulted from MRI with histology examination(r=0.688,0.642;P=0.001,0.002).Conclusions High resolution MR vessel wall imaging technique may evaluate and follow up the plaque burden in the early stage of atherosclerosis.
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Background and purpose:Cytotoxic T lymphocyte (CTL) plays a vital role in the process of anti-tumor immunology. The aim of this study was to investigate whether changes in concentration of IL-2 (50, 200 and 1 000 U/mL) would affect the sub-population and cytotoxic function of cells cultivated by peptide-specific CTL induction systemin vitro and also observe whether using the concentration of IL-2 at a range of 50-1 000 U/mL isbeneifcial to regulatory cells (Tregs) enrichment.Methods:Peripheral blood from 10 healthy donors and 10 cancer patients that were HLA-A2 positive, were collected in the study. HLA-A2 restricted CTL epitope P321 (ILIGETIKI) derived from COX-2 pulsed with different concentrations of IL-2 were used to induce peptides-speciifc CTLin vitro. Flow cytometry was performed to analyze the proliferative capability, the proportion of different T-cell subsets, and secretion of perforin, granzyme B and IFN-γ. IFN-γ secretion was assessed by ELISpot assay.Results:High concentration of IL-2 increased the proliferative activity. The percentage of CD4+ T cells of cancer patient group was signiifcantly higher than that of healthy donor group, while the percentage of CD8+ T cells of cancer patient group was signiifcantly lower than that of healthy donor group. And there was no signiifcant difference in the percentages of CD4+ T cells, CD8+ T cells and Tregs among groups with different IL-2 concentrations. No difference was seen in cytokine (perforin, granzyme B, IFN-γ) secretion capacity of CD8+ T cells. ELISpot study revealed that high-dose IL-2 resulted in the increasing of IFN-γ secretion.Conclusion:The sub-population and the function of cells cultured by peptide-speciifc CTL induction systemin vitro are not affected by different concentrations of IL-2. Furthermore, high concentrations of IL-2 (50-1 000 U/mL) do not provide the enrichment for Tregs. Higher concentration of IL-2 is likely to cause high secretion of IFN-γ in ELISpot assay. In order to exclude the distraction of NK cells or NKT cells, the concentration of 50 U/mL is better choice.
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Objective To investigate the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of immunoglobulin G4 associated cholangitis (IAC) and the key points for identification and diagnosis.Methods The clinical data of 11 patients with IAC who were admitted to the Peking University People's Hospital from January 2013 to January 2015 were retrospectively analyzed.Patients received plain and enhanced scan of CT,plain and enhanced scan of MRI and magnetic resonance cholangiopancreatography (MRCP) examination before hormone therapy.Patients were followed up by telephone interview and outpatient examination till January 2015,and their imaging data were evaluated.Results Of the 11 patients,7 patients received plain and enhanced scan of CT,6 patients received plain and enhanced scan of MRI and 7 patients received MRCP examination.The results of CT and MRI examinations showed bile duct segmental stricture and non-obliteration of cavity were detected in the 11 patients.Diffused thickening of intrahepatic and extrahepatic bile duct and no correlation between the thickening and the stricture of the bile duct was detected in the 8 patients.The bile duct wall of 3 patients was locally thickened,including 2 thickened common bile duct wall at the region of the head of the pancreas and 1 thickened hilar bile duct.The results of MRI showed low T2WI signal of the bile duct wall in 7 patients and equal signal in 4 patients.Enhanced signal in the bile duct wall was detected in the delayed phase in 11 patients by enhanced scan of CT and MRI,and 8 of the 11 patients had enhanced signal in the arterial,venal and delayed phase.Nine patients were complicated with autoimmune pancreatitis (3 of them were with concomitant renal disease),and 1 patient was only complicated with immune-related renal disease.Enlargement of lymph nodes was detected around the pancreas in 3 patients,while no enlargement of lymph nodes was detected in 8 patients.Among all the 11 patients undergoing hormone therapy,8 patients were followed up for a median time of 13 months (range,6-18 months),including 7 patients with good recovery and 1 patient with recurrence of IAC.Conclusion Diffused and irregular thickening and stenosis but not occlusion of biliary duct,the thickening and stenosis which are detected by CT and MRI examinations is relatively independent,and associated with autoimmune pancreatitis and other organs involved may be helpful to make a diagnosis of IAC.
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Objective To study the change of Insulin-like growth factor 1(IGF-1)and Epidermal growth factor(EGF)level in blood of newborns with asphyxiated.Investigation the effect of stomach-intestine hormone to newborns asphyxiated.Methods plasma IGF-1,EGF level of 48 neonatal asphyxia and 36 normal newborns(1d,3d,7d)were tested by radioimmunoassay.Result In comparision with normal neonatal,IGF-1,EGF level of neonatal asphyxia reduced significantly(P
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Objective In order to provide the reasons for local injecting Xiaozhiling to treat malignant tumors. Methods 10 mice were subcutaneosly injected with S 180 Tumor cell to create tumor models and then Xiaozhiling 10ml/kg were intratumorly injected for 3 times.Finally,observation and comparison were made for the pathologic changes under optic and electronic microscopies. Results The results showed that Xiaozhiling had strong antitumor effect on S 180 tumor(adquate rate was 37.3%).Pathalogical exemination revealed that the tumor tissue necrosed obviously,some wesslincataneous cells breaked up, red blood cells extravasation,micro blood clots formed.No changes occurred in the control group. Conclusions Xiaozhiling could be a new drug for clinical treatment of malignant tumor.