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Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4+ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4+ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
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Animales , Humanos , Ratones , Linfocitos T CD4-Positivos/patología , Diferenciación Celular , Encefalomielitis Autoinmune Experimental/metabolismo , Ratones Endogámicos C57BL , Esclerosis Múltiple , Células TH1/patologíaRESUMEN
Objective:To explore the application potential of 18F-Asp-Glu-val-Asp (DEVD)-Cys(StBu)-PPG(CBT)-AmBF 3 ( 18F-1; PPG: propargyl-glycine; CBT: 2-cyanobenzothiazole; AmBF 3: ammoniomethyl-trifluoroborate) PET imaging in early monitoring of triple-negative breast cancer (TNBC) radiotherapy response. Methods:Ten MDA-MB-231 tumor bearing nude mice models were constructed and divided into radiotherapy group ( n=5) and non-radiotherapy group ( n=5) by random sampling method. The radiotherapy group was treated with single irradiation at a dose of 8 Gy. 18F-1 microPET imaging was performed in the radiotherapy and non-radiotherapy groups, and the tumor uptake and muscle uptake in 2 groups at different time points (2.5, 7.5, 12.5, 17.5, 22.5, 27.5, 32.5, 37.5, 42.5, 47.5, 52.5, 57.5 min after injection) were analyzed. The specific uptake of the probe in apoptotic cells was verified by radioautography, HE staining and immunofluorescent staining. Repeated measures analysis of variance and one-way analysis of variance were used to analyze data. Results:18F-1 microPET imaging showed that there was significant difference between tumor uptake and muscle uptake in radiotherapy group ( F=20.27, P=0.011). The uptake of radiotherapy group was the highest at 7.5 min after injection ((4.64±0.35) percentage activity of injection dose per gram of tissue(%ID/g)). There was no significant difference between tumor uptake and muscle uptake in the non-radiotherapy group ( F=1.81, P=0.215). The tumor/muscle (T/M) ratio of radiotherapy group was higher than that of non-radiotherapy group ( F=31.95, P=0.005), with the highest at 47.5 min after injection (2.49±0.46). Radioautography showed that the tumor radioactivity in radiotherapy group was higher than that of muscle in radiotherapy group, and was also higher than tumor and muscle radioactivies in non-radiotherapy group ( F=116.79, P<0.001). HE staining and immunofluorescent staining verified that 18F-1 could specifically detect the activity of caspase-3 activated in tumor cells after radiotherapy. Conclusion:18F-1 can specifically recognize the activated caspase-3 after TNBC radiotherapy, and monitor radiotherapy response at the molecular level by apoptosis PET imaging.
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Objective@#To prepare manganese-doped carbon quantum dots (Mn-CDs) dual-modal nanoprobe for fluorescent-magnetic imaging, and evaluate its characteristics and potential on fluorescence imaging and MRI.@*Methods@#Mn-CDs were synthesized at 150 ℃. The form, diameter, component, fluorescent capability, T1 relaxation rate, stability and cytotoxicity of Mn-CDs in vivo were verified. The fluorescence imaging of HO-8910 tumor-bearing mice was performed on small animal imager, and the whole-body enhanced imaging was performed on 3.0 T MRI scanner. One-way analysis of variance was used to analyze the data.@*Results@#The Mn-CDs with the diameter of (4.64±0.85) nm showed a well-defined spherical morphology. The fluorescent spectra of Mn-CDs exhibited that the excitation maximum was at 360 nm and the emission maximum was at 440 nm. The T1 relaxation rate was (3.26±0.04) mmol·L-1·s-1. The Mn-CDs had good stability of fluorescent and magnetic imaging capability at 0, 0.25, 0.5, 0.75, 1.0 and 2 months at room temperature with no significant differences of fluorescent and magnetic signals (F=1.566 and 0.987, both P>0.05). After injection of 200 μl Mn-CDs (15 g/L), mice were all alive and had no viscera damage. The tumor could be observed obviously on fluorescence imaging at 5 min. Enhanced MRI showed that the tumor was unevenly enhanced and Mn-CDs were mainly cleared away through urinary system.@*Conclusion@#Mn-CDs are stable and have good potential on fluorescence imaging and MRI, which provides a promising multimodal imaging method for tumor detection and monitoring.
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Objective To prepare manganese-doped carbon quantum dots ( Mn-CDs) dual-modal nanoprobe for fluorescent-magnetic imaging, and evaluate its characteristics and potential on fluorescence imaging and MRI. Methods Mn-CDs were synthesized at 150 ℃. The form, diameter, component, fluo-rescent capability, T1 relaxation rate, stability and cytotoxicity of Mn-CDs in vivo were verified. The fluores-cence imaging of HO-8910 tumor-bearing mice was performed on small animal imager, and the whole-body enhanced imaging was performed on 3.0 T MRI scanner. One-way analysis of variance was used to analyze the data. Results The Mn-CDs with the diameter of (4.64±0.85) nm showed a well-defined spherical morpholo-gy. The fluorescent spectra of Mn-CDs exhibited that the excitation maximum was at 360 nm and the emission maximum was at 440 nm. The T1 relaxation rate was (3.26±0.04) mmol·L-1·s-1. The Mn-CDs had good stability of fluorescent and magnetic imaging capability at 0, 0.25, 0.5, 0.75, 1.0 and 2 months at room tem-perature with no significant differences of fluorescent and magnetic signals ( F=1. 566 and 0. 987, both P>0. 05) . After injection of 200 μl Mn-CDs ( 15 g/L) , mice were all alive and had no viscera damage. The tumor could be observed obviously on fluorescence imaging at 5 min. Enhanced MRI showed that the tumor was unevenly enhanced and Mn-CDs were mainly cleared away through urinary system. Conclusion Mn-CDs are stable and have good potential on fluorescence imaging and MRI, which provides a promising multimodal im-aging method for tumor detection and monitoring.
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Objective To investigate the application value of inferior vena cava venography in correlation between the subtypes of inferior vena cava obstruction and calcifications at the obstruction in Budd-Chiari syndrome (BCS).Methods The retrospective cross-sectional study was conducted.The clinical data of 41 patients with BCS who were admitted to the Affiliated Hospital of Xuzhou Medical University between January 2009 and December 2016 were collected.There were 29 males and 12 females,aged (53±10)years,with a range of 34-70 years.Forty-one BCS patients underwent computed tomography (CT),inferior vena cava CT venography and digital subtraction angiography (DSA) within 2 weeks.Balloon dilatation and (or) endovascular stent implantation of inferior vena cava were performed according to calcification morphology and location of the inferior vena cava obstruction detected by DSA.Observation indicators:(1) calcifications of inferior vena cava obstruction;(2) intraoperative situations of interventional therapy;(3) correlation between the subtypes of inferior vena cava obstruction and calcifications at the obstruction;(4)follow-up and survival situations.Follow-up using outpatient examination of inferior vena cava venography was performed at 3,6,12,24,36,48 months postoperatively to detect postoperative clinical manifestations,complications and survival situations up to December 2018.Measurement data with normal distribution were represented as Mean±SD.Count data were represented as absolute number and comparison between groups was analyzed using the chi-square test.The likelihood ratio test was used to analyze the correlation between the subtypes of inferior vena cava obstruction and calcifications at the obstruction.The degree of correlation was detected by Cramer's V contingency coefficient.Results (1)Calcifications of inferior vena cava obstruction:of 41 patients,17 had no calcification at the inferior vena cava obstruction and 24 had calcifications at the obstruction.Calcification location in 24 patients:there were 17,4 and 3 patients with proximal,distal,both proximal and distal calcifications at the inferior vena cava obstruction,respectively.Calcification morphology:punctate and irregular calcifications were detected in 20 and 4 patients,respectively.Calcification distribution:20,3 and 1 patients had scattered,cluster and diffuse distribution,respectively.(2) Intraoperative situations of interventional therapy:of 41 patients,21 underwent balloon dilatation and 20 underwent balloon dilatation combined with endovascular stent implantation.Two patients were detected hematoma at the puncture site of right femoral vein and treated using pressure dressing.One patient encountered rupture of balloon due to diffuse calcifications at the inferior vena cava obstruction and was improved after continual replace of balloon for 3 times.One patient had pulmonary embolism caused by detachment of the thrombosis at the distal obstruction during the balloon dilatation and was given anticoagulation therapy combined with thrombolytic therapy using large-dose of urokinase.The other 37 patients underwent successful interventional therapy without exceptional circumstances.(3) Correlation between the subtypes of inferior vena cava obstruction and calcifications at the obstruction:of 24 patients with calcifications at the inferior vena cava obstruction,13 had membrane obstruction,7 had segmental obstruction and 4 had fenestrated membrane obstruction.Of 17 patients without calcifications at the inferior vena cava obstruction,3 had membrane obstruction,13 had segmental obstruction and 1 had fenestrated membrane obstruction.The likelihood ratio test showed that the subtypes of inferior vena cava obstruction were associated with calcifications at the obstruction (x2=9.293,P<0.05),with the correlation coefficient V as 0.466.Further analysis showed a correlation between membrane obstruction of inferior vena cava and calcifications at the inferior vena cava obstruction (x2=8.121,P<0.05),no correlation between segmental obstruction and calcifications at the inferior vena cava obstruction,also no correlation between fenestrated membrane obstruction and calcifications at the inferior vena cava obstruction (x2=3.395,0.004,P>0.05).(4) Follow-up and survival situations:41 patients were followed up for 24.0-48.0 months,with a median time of 37.1 months.Postoperative ultrasound showed smooth backflow in the inferior vena cava,different degree of improvements in the lower limb swelling and varicosity in 38 patients.Embolisms in the inferior vena cava obstruction remained existent in 3 patients,1 of whom showed significant decreasing of embolisms.There were 2 patients found restenosis and undergoing endovascular stent implantation.All the 41 patients survived.Conclusions The subtypes of inferior vena cava obstruction are associated with calcifications at the obstruction in BCS.Inferior vena cava venography evaluating calcifications at the inferior vena cava obstruction in BCS can be helpful for diagnosing the subtypes of inferior vena cava obstruction and guiding its interventional therapy.
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Objective To explore the limits of fluid-inversion prepared diffusion weighted imaging (FLIPD) in detection of acute cerebral ischemic lesions.Methods From January 2012 to March 2014,forty-nine patients (33 males,16 females,age (55.6± 12.3) years) clinically diagnosed as transient ischemic attack (TIA) were included.Patients underwent brain MRI (conventional diffusion weighted imaging (DWI) and FLIPD) within 3 d after the onset of TIA.The detection ability of MRI with the two sequences was compared,and the relative signal intensity (rSI) and apparent diffusion coefficient (ADC) of acute ischemic lesions based on two sequences were compared.Kappa test and two-sample t test were used to analyze the data.Results A total of 87 acute ischemic lesions were detected in 21 patients by conventional DWI,and 54 were detected in 19 patients by FLIPD (Kappa=0.916,P<0.05).The rSI of ischemic lesions on FLIPD was significantly lower than that on conventional DWI (1.37±0.22 vs 1.57±0.26;t=6.647,P<0.001).The ADC value of ischemic lesions on FLIPD was slightly lower than that on conventional DWI:(0.54 ±0.10) ×10-3 mm2/s vs (0.57±0.13)×10-3 mm2/s (t=2.120,P<0.05).The missed lesions on FLIPD were located in the white matter (n =18),cerebellum and brainstem (n =8),and the cortex (n =7).Conclusions A slight diffuse abnormality may be missed on FLIPD,so this method is not suitable for the detection of acute ischemic lesions.FLIPD technology still needs improvement.
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Objective To fabricate manganese-doped carbon quantum dots(Mn-CDs)@anti-human epididymis protein 4(HE4)monoclonal antibody(Mn-CDs@Anti-HE4 mAb)dual-modal fluorescent-magnetic nanoprobe for ovarian cancer cells targeting imaging,and evaluate its potential on fluorescent imaging and MRL Methods Mn-CDs were synthesized at 150 ℃ with solvothermal method.The average diameter,fluorescent capability and MRI efficiency were determined.The cytotoxicity of Mn-CDs in vitro was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)assay with HO-8910 ovarian cancer stem cells and EA.hy926 human umbilical vein endothelial cells.Mn-CDs@Anti-HE4 mAb was fabricated with condensation reaction and characterized by ultraviolet(UV)absorption spectra.Fluorescence imaging and MRI in vitro was performed for cancer cell-targeting study.One-way analysis of variance and the least significant difference t test were used to analyze the data.Results The Mn-CDs with diameter of(4.64±0.85)nm showed a well-defined spherical morphology.The fluorescent spectra of Mn-CDs exhibited a typical excitation-dependent behavior with an excitation maximum at 360 nm and emission maximum at 440 nm.The T1 relaxation rate was(3.26±0.04)mmol ? L-1 ? s-1.The cytotoxicity tests in vitro showed that the survival rates of HO-8910 cells and EA.hy926 cells were both significantly different after treated with different concentrations of Mn-CDs(F= 1 947.509,260.174,both P<0.05),and there was no cytotoxicity in both HO-8910 cells and EA.hy926 cells at concentrations of MnCDs within 0-2.5 mg/ml(all P>0.05),while the survival rates of the two kinds of cells were descended with the increasing of concentration within 3.0-4.5 mg/ml(P<0.05).Mn-CDs@Anti-HE4 mAb could target HO-8910 cells on fluorescence imaging and MRI.Conclusions Mn-CDs@Anti-HE4 mAb,with good potential on fluorescence imaging,MRI and targeting ability,is successfully synthesized.It may provide a new method for early diagnosis of ovarian cancer.
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Objective@#To investigate the feasibility of contrast-enhanced computer tomography (CT) texture analysis in predicting early recurrence after transarterial chemoembolization (TACE) in patients with liver cancer.@*Methods@#A retrospective analysis was performed for 47 patients with liver cancer confirmed by liver biopsy and digital subtraction angiography who underwent upper abdominal contrast-enhanced CT scan before TACE, and according to the presence or absence of focal recurrence within half a year, these patients were divided into early recurrence (ER) group and non-early recurrence (NER) group. The texture analysis was used to delineate tumor boundary layer by layer on the axial contrast-enhanced CT image before liver cancer surgery, and related parameters of tumor heterogeneity, including entropy, mean, non-uniformity, skewness, and kurtosis, were obtained. The independent samples t-test was used for comparison of texture parameters between the two groups. The receiver operating characteristic (ROC) curve was used for the analysis of entropy, mean, and non-uniformity, and the area under the ROC curve (ROC), optical cut-off value, sensitivity, and specificity were calculated to evaluate the efficiency of texture analysis in predicting early focal recurrence after TACE.@*Results@#There were 20 patients in the ER group and 27 in the NER group. The ER group had a maximum major axis length of 88.2±36.3 mm and a maximum minor axis length of 41.4±21.4 mm, and the NER group had a maximum major axis length of 66.9±30.2 mm and a maximum minor axis length of 29.3±19.8 mm; the ER group had significantly higher maximum major and minor axis lengths than the NER group (t = 4.89 and 4.62, P < 0.001). The ER group had significantly higher entropy and non-uniformity values than the NER group, and there were no significant differences in skewness and kurtosis between the two groups. Entropy, non-uniformity, and mean had high efficiency in predicting early recurrence after TACE, and the optimal cut-off value of entropy was 4.135.@*Conclusion@#Volumetric texture analysis of contrast-enhanced CT images before liver cancer surgery has a high value in predicting early recurrence after TACE.
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Objective To study the intra-and extra-hepatic collateral pathways in various types of Budd-Chiari syndrome (BCS) using liver acceleration volume acquisition (LAVA) enhanced MRI.Methods The clinical data and imaging findings of 240 patients with BCS were collected and analyzed.The types of BCS confirmed by DSA.Intra-and extra-hepatic collateral pathways were studied using LAVA enhanced MRI with a 3.0T scanner.Correlations of the intra-/extra-hepatic collateral pathways with the types of BCS were analyzed using the Chi-square test.Then,the degrees of correlation were calculated by the Cramet correction coefficient of contingency.Results Among the 240 patients,DSA confirmed 60 patients to have hepatic vein occlusion,39 patients to have inferior vena cava occlusion and 141 patients to have both hepatic vein and inferior vena cava occlusion.MRI demonstrated dilated accessory hepatic veins in 157 patients,intra-hepatic communicating branches in 69 patients,inferior phrenic veins in 43 patients,superficial epigastric veins in 135 patients,umbilical veins in 94 patients and hemiazygos/azygos veins in 195 patients.Accessory hepatic veins and hemiazygos/azygos veins as collateral pathways were associated with the types of BCS (x2 =30.239,P < 0.05;x2 =51.295,P < 0.05,respectively).The degrees of correction were 0.355 and 0.462,respectively.Accessory hepatic veins as collateral pathways were most common in the mix type,accounting for 79.4%.Hemiazygos/azygos veins were most common in the inferior vena cava occlusion type and the mix type,accounting for 92.3% and 91.5 %,respectively.Conclusions Accessory hepatic veins and hemiazygos/azygos veins as collateral pathways were associated with the types of BCS,while the intra-hepatic communicating branches,inferior phrenic veins,superficial epigastric veins and umbilical veins were not correlated with the types of BCS.LAVA may help to diagnose and determine the best choice of treatment for the various types of BCS.