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Objective To explore the effect of formononetin on immunity of mice with transplanted H22 hepatocarcinoma. Methods Male C57BL/6 mice were subcutaneously inoculated with H22 cells (4×105) to establish a tumor-bearing mouse model. The mice were treated with formononetin [10 mg/(kg.d)] or [50 mg/(kg.d)] for 28 days, and then the tumor inhibition rate was calculated. Carrilizumab was used as a positive control drug. The expressions of CD8, granzyme B and forkbox transcription factor 3 (FOXP3) in HCC tissues were analyzed by immunohistochemical staining. The mRNA and protein expression of programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) in HCC tissues were detected by real-time PCR or Western blot analysis, respectively. The serum levels of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) were detected by ELISA. Results Formononetin increased the tumor inhibition rate and the positive rate of CD8 and granzyme B staining in tumor-bearing mice. There was no significant difference in the positive rate of FOXP3 staining in tumor tissues of mice in each group. Formononetin decreased the levels of IL-10 and TGF-β in serum of tumor-bearing mice, and decreased the relative expression of mRNA and protein of PD-1 and PD-L1 in tumor tissue of tumor-bearing mice. Conclusion Formononetin can activate CD8+ T cells and reduce the release of immunosuppressive factors in regulatory T cells by blocking PD-1/PD-L1 pathway and play an antitumor role.
Subject(s)
Male , Animals , Mice , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Interleukin-10/genetics , B7-H1 Antigen , Granzymes/genetics , Programmed Cell Death 1 Receptor/metabolism , CD8-Positive T-Lymphocytes/metabolism , Mice, Inbred C57BL , Transforming Growth Factor beta/genetics , RNA, Messenger/metabolism , Forkhead Transcription Factors/genetics , Cell Line, TumorABSTRACT
To investigate the values of orbital single photon emission computed tomography/computerized tomography (SPECT/CT) with 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) on the evaluation of lacrimal gland inflammation in patients with thyroid associated ophthalmopathy (TAO). Methods: A total of 58 TAO patients were retrospectively recruited for this study, all of whom were categorized into all active group and all inactive group based on the clinical active score (CAS). Another 12 patients with the negative images on SPECT/CT served as a normal control group (NC). All patients were undergone the 99mTc-DTPA orbit SPECT/CT. Quantitative parameters of lacrimal gland including width, length, volume, and the count ratio of region of interest (ROI) drawn on lacrimal gland to the region of occipital brain (target/non-target ratio, T/NT), were measured on axial and coronal slices, respectively. Quantitative parameters were compared among the 3 groups, and the diagnostic value on discrimination of TAO patients from inactive to active ones was evaluated. Results: All parameters in TAO patients (except the length on coronal slices and the mean radioactive counts of axial T/NT in the TAO inactive group) were much greater than those in the NC group (P<0.05). All parameters in the TAO active group (except the length on axial and coronal slices) were much greater than those in the TAO inactive group (P<0.05). There were significant lineal positive correlations between the parameters in all TAO patients (except the length on coronal slices ) and CAS. The best diagnostic value was detected by the max radioactive counts of axial T/NT (area under the curve=0.82, P<0.01). Conclusion: As an invasive imaging modality, 99mTc-DTPA orbital SPECT/CT is helpful to estimate the lacrimal gland inflammation and to assess the disease activity in TAO patients.
Subject(s)
Humans , Graves Ophthalmopathy , Inflammation , Lacrimal Apparatus , Orbit , Retrospective Studies , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray ComputedABSTRACT
Objective:To evaluate the inflammatory activity in thyroid associated ophthalmopathy (TAO) by 99mTc-diethylene triamine pentaaceticacid (99mTc-DTPA) orbital single-photon emission computed tomography (SPECT)/CT.Methods:A total of 48 patients were enrolled from Xiangya Hospital of Central South University between October 2016 and March 2017.According to clinical active score (CAS),93 eyes were divided into a TAO active group (n=72) and a TAO inactive group (n=21).All patients underwent 99mTc-DTPA orbital SPECT/CT examination,and the DTPA uptake in extraocular muscle belly was supposed to be positive.The results of 99mTc-DTPA orbital SPECT/CT examination were compared with those of CAS score evaluation.Results:The uptake rate (UR) of 99mTc-DTPA in the TAO active group was higher than that in the TAO inactive group (P＜0.01).There was a linear positive correlation between UR and its CAS scores in all patients (r=0.767,P＜0.01).Five cases (7 eyes) showed inconsistent results between 99mTc-DTPA orbital SPECT/CT examination and CAS score.Among the 7 eyes,6 eyes showed myocarditis lesions in 99mTc-DTPA orbital SPECT/CT examination while its CAS was no more than 3;meanwhile,there was 1 eye with CAS＞3,but 99mTc-DTPA orbital SPECT/CT examination showed negative myocarditis lesions.Conclusion:99mTc-DTPA orbital SPECT/CT is consistent with the CAS score in evaluation of the disease activity of TAO;99mTc-DTPA orbital SPECT/CT may be more objective and accurate to evaluate TAO than CAS.
ABSTRACT
To compare diagnostic value of 4 kinds of target-to-nontarget ratio (T/NT), and to choose a better one to assess thyroid associated ophthalmopathy (TAO) activity. Methods: The clinical data were collected for 29 newly-diagnosed patients (58 eyes) with TAO who underwent orbital 99mTc-DTPA single photon emission computed tomography/computed tomography (SPECT/CT) fusion images according to the clinical activity score (CAS). They were divided into an active group (18 cases, 36 eyes), an inactive group (11 cases, 22 eyes), and a control group (9 cases, 18 eyes). Diagnostic value of orbital/occipital lobe radioactive uptake count ratio (T/NT1), orbital/occipital radioactive uptake count ratio (T/NT2), orbital/thalamus radioactive uptake count ratio (T/NT3), and orbital/cerebellar radioactivity uptake count ratio (T/NT4) were calculated, and the CAS of Spearman rank correlation and receiver operating characteristic (ROC) curve were analyzed. Results: T/NT1, T/NT2 and CAS were correlated (r1=0.873, r2=0.527; P0.05). Area under the ROC curve of T/NT1 was 0.860, area under the ROC curve of T/NT2 was 0.581, and the accuracy for T/NT1 on TAO activity was good. T/NT1=9.74 could be used as active threshold for judge of TAO in patients. Conclusion: There is a good correlation between T/NT1 and CAS. TAO activity assessment possesses high diagnostic value, and SPECT/CT together with imaging anatomical location is more accurate.
Subject(s)
Humans , Case-Control Studies , Graves Ophthalmopathy , Diagnostic Imaging , Orbit , Diagnostic Imaging , ROC Curve , Radiopharmaceuticals , Statistics, Nonparametric , Technetium Tc 99m Pentetate , Tomography, Emission-Computed, Single-Photon , MethodsABSTRACT
Acute-on-chronic liver failure (ACLF) is a severe liver disease with high mortality in China. Early diagnosis could reduce complications and improve the survival rate. In the present review, the definition, etiology, and pathogenesis related to inflammatory response, reactive oxygen species, and metabolism are reviewed. Also, the new approaches to the treatment of ACLF and prognostic factors are summarized. Generally, the development of ACLF is considered to be life-threatening for patients. Therefore, a universal definition of ACLF should be proposed, which would provide good guidance and standard for the clinical diagnosis and treatment of ACLF in China. In addition, the risk factors for ACLF in patients with chronic liver diseases need to be determined by prospective studies.