ABSTRACT
Objective:To investigate the synergistic effects and molecular mechanisms of dihydroartemisinin(DHA) and sorafenib(SOR) in inducing ferroptosis in anaplastic thyroid cancer(ATC) cells.Methods:CCK-8 and flow cytometry assays were performed to detect the effects of DHA and SOR on the proliferation and ferroptosis of ATC cells(CAL-62). Real-time fluorescence quantitative PCR and Western blotting assays were performed to detect the expressions of ferroptosis-related genes glutathione peroxidase 4(GPX4), solute carrier family 7 member 11 gene(SCL7A11), lipoxygenase-15(LOX-15), and p53. The levels of iron death intermediate metabolites including lactate dehydrogenase(LDH), glutathione(GSH), malondialdehyde(MDA), ferrous ion(Fe 2+ ), nitric oxide(NO), and reactive oxygen species(ROS)were measured by corresponding assay kits. The corresponding inhibition of DHA and SOR on ATC in vivo was analyzed in a tumor model in nude mice. Results:Compared with the control group, DHA, SOR, and DHA+ SOR treatment significantly inhibited cell proliferation and apoptosis in a dose-dependent manner( P<0.001), with increased LDH, Fe 2+, MDA, and ROS contents and reduced GSH activity( P<0.001), which were promoted by ferrous sulfate(FeSO 4)and reversed by ferroptosis inhibitor-1. Compared with the control group and the drug monotherapy group, 15-LOX-2 and p53 expressions were upregulated in DHA+ SOR group while GPX4 and SCL7A11 expressions were decreased( P<0.001), without significant difference in 15-LOX-1 protein content. In addition, NO level was significantly increased in DHA+ SOR group( P<0.001). DHA and SOR inhibited tumor growth of ATC in vivo. Conclusion:DHA and SOR synergistically induced ferroptosis via upregulating the expression of 15-LOX-2 gene and inhibiting NO synthesis in ATC cells.
ABSTRACT
Objective:To explore the association between body mass index (BMI) and the incidence of thyroid nodules, the clinical characteristics and efficacy evaluation of differentiated thyroid cancer (DTC), respectively.Methods:Clinical data of 1 375 healthy people (1 031 males, 344 females, age: (43.5±10.6) years) who underwent routine physical examination (PE) and 1 450 patients (490 males, 960 females, age: (44.3±12.4) years) with medium-high risk DTC in Tianjin Medical University General Hospital from April 2016 to July 2020 were analyzed retrospectively. PE and DTC patients were classified into underweight group (BMI<18.5 kg/m 2), normal weight group (18.5≤BMI<24.0 kg/m 2), overweight group (24.0≤BMI<28.0 kg/m 2) and obesity group (BMI≥28.0 kg/m 2) respectively. χ2 test was employed to analyze the relation between BMI and thyroid nodules (with/without), BMI and clinical characteristics and efficacy evaluation of DTC, respectively. Logistic regression analysis was used to analyze the independent risk factors for the occurrence of thyroid nodules and the aggressiveness of DTC. Results:Among PE, there were 779 cases with nodules, and 596 cases without nodules. Comparing with those without nodules, more overweight and obese were found in PE cases with nodules (42.1%(328/779) vs 37.2%(222/596), 24.5%(191/779) vs 20.5%(122/596); χ2=13.42, P=0.004). Higher risk of developing thyroid nodules was related with older age and lower thyroid stimulating hormone (TSH) level (odds ratio ( OR): 1.044, 0.919, 95% CI: 1.029-1.060, 0.845-0.999; P<0.001, P=0.046). People with high-risk nodules were more likely to be obese than those with intermediate and lower risk nodules (5/15 vs 24.3% (186/764); χ2=21.11, P<0.001). Among 1 450 DTC patients, comparing with patients with normal weight, patients in the overweight and obesity groups were more likely to have central regional lymph node metastasis ( OR: 1.418, 1.427, 95% CI: 1.075-1.870, 1.044-1.952; P values: 0.013, 0.026), and patients in obese group were with greater risk of lesions being bilateral ( OR=0.696, 95% CI: 0.519-0.934; P=0.016). BMI was not related with the efficacy evaluation of DTC ( χ2=9.13, P=0.425). Conclusions:The incidence of thyroid nodules in people with high BMI is higher. DTC patients with high BMI may have more aggressive incidence. But BMI has no correlation with the efficacy evaluation of DTC patients after treatment.
ABSTRACT
Objective:To explore new methods of treating Graves′ disease (GD) by targeting thyroid stimulating hormone receptor (TSHR) and intercellular adhesion molecule-1 (ICAM-1).Methods:The small interfering RNA (siRNA) targeting TSHR and the ICAM-1 monoclonal antibody (mAb) were designed and synthesized. Thirty GD model mice were randomly divided into siRNA treatment group, ICAM-1 mAb treatment group, and untreated GD group (10 mice in each group), and 10 normal mice were taken as blank control. Serum thyroxine (T 4), thyroid stimulating hormone (TSH), TSH receptor-stimulating antibody (TSAb) and TSH-stimulation blocking antibody (TSBAb) were measured before and after treatment. At the end of the treatment, body mass and heart rate of mice in each group were measured, and thyroid uptake of 99Tc mO 4-, thyroid size and pathological changes were evaluated. Independent-sample t test, paired t test and one-way analysis of variance were used to analyze data. Results:After three treatments, the body mass of mice in siRNA group and ICAM-1 mAb group were significantly lower than that of normal mice ( F=3.50, P=0.025); the heart rates of the mice in two groups were significantly lower than that of untreated GD mice ( F=24.73, P<0.001). Heart rate of mice treated with siRNA decreased significantly, close to that of normal mice. After treatment, the serum T 4((27.58±1.94) vs (65.71±6.89) μg/L, (27.24±3.50) vs (70.84±8.46) μg/L), TSAb ((331.44±43.38) vs (457.33±45.85) mU/L, (275.16±45.80) vs (443.91±42.32) mU/L) and TSBAb ((13.94±1.11) vs (15.83±5.92) mU/L, (14.59±1.02) vs (17.05±6.16) mU/L) levels of mice in both siRNA group and ICAM-1 mAb group significantly decreased ( t values: 4.45-10.87, all P<0.05), while the serum TSH levels of mice in two groups significantly increased ((0.13±0.05) vs (0.04±0.05) mU/L, (1.46±0.34) vs (0.06±0.03) mU/L; t values: -2.22, -5.87, P values: 0.007, <0.001). The elevated TSH level and decreased TSAb level of mice treated with ICAM-1 mAb were significantly different from those treated with siRNA ( t values: 1.03, -1.63, P values: 0.002, 0.031). After treatment, the uptake of 99Tc mO 4- in part of the thyroid lobes of mice was decreased, and the enlargement degree of the corresponding lobes was reduced. The thyroid pathology of mice in the treated groups showed that the absorption vacuoles of thyroid follicles were reduced, and the phenomenon of thinner colloids was improved. No obvious damage was observed in the heart, liver and kidneys of the mice. Conclusions:Both the siRNA targeting TSHR and ICAM-1 mAb have therapeutic effects on GD model mice. The siRNA is better at controlling heart rate, and ICAM-1 mAb is better at increasing TSH and decreasing TSAb. Each of the above treatment methods is safe and effective, which can provide new ideas for GD targeted therapy.
ABSTRACT
Objective:To evaluate the health risk of fluoride in rural drinking water in drinking-water-borne endemic fluorosis(referred to as drinking-water-borne fluorosis) areas of Shaanxi Province, and to provide scientific basis for the formulation of water improvement and fluoride reduction measures.Methods:The fluoride monitoring results of rural drinking water in Guanzhong Plain and Loess Plateau of Northern Shaanxi in drinking-water-borne fluorosis areas of Shaanxi Province in 2020 were collected from the "National Drinking Water Quality and Sanitation Monitoring Information System". Using the health risk assessment method recommended by the United States Environmental Protection Agency (USEPA), the level of fluoride exposure of adults in fluorosis areas through drinking water was evaluated, and the health risk value was calculated.Results:A total of 4 342 rural drinking water samples from drinking-water-borne fluorosis areas were monitored. The overall compliance rate of fluoride in water quality was 95.39% (4 142/4 342), and the fluoride content median was 0.470 mg/L; the health risk value was 0.368, and the non-carcinogenic risk was low. A total of 200 water samples with fluoride exceeding the standard were detected, and the fluoride content median was 1.450 mg/L; the health risk value of the fluoride excess water samples was 1.135, indicating a high non-carcinogenic risk. There were significant differences in fluoride content in rural drinking water between different regions, water sources and treatment methods ( H = - 7.73, - 7.60, 34.40, P < 0.05). Conclusions:The non-carcinogenic risk of fluoride exposure of adults in drinking-water-borne fluorosis areas through drinking water in Shaanxi Province is relatively low, and the non-carcinogenic risk caused by water samples with excessive fluoride is relatively high. In the future, it is necessary to continue to promote the comprehensive prevention and control measures focusing on improving water and reducing fluoride.
ABSTRACT
Objective:To analyze the short-term effect of targeted drugs on quality of life in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC).Methods:From February 2020 to April 2022, 19 RAIR-DTC patients (10 males, 9 females; age (54.5±14.5) years) who received targeted drugs therapy (sorafenib, lenvatinib or anlotinib) in Tianjin Medical University General Hospital were prospectively enrolled. The thyroglobulin (Tg) levels prior and 1, 3, 6 months post the targeted treatment, and the adverse events were measured and recorded. Response evaluation criteria in solid tumors (RECIST) 1.1 version was used to evaluate the treatment response. The quality of life based on five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) was monitored prior and 3 months post the targeted treatment, and the prevalence rates of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were analyzed, and the scores of health assessment were assessed. Paired t test, Kruskal-Wallis rank sum test and χ2 test were used to analyze data. Results:The prevalence rates of mobility (8/19), self-care (6/19), usual activities (10/19), pain/discomfort (10/19), and anxiety/depression (12/19) in 3 months post treatment were higher than those prior treatment (1/19, 1/19, 1/19, 2/19, 2/19; χ2 values: 4.38-11.31, all P<0.05). The score of health assessment prior treatment was (84.37±6.25), which was higher than that at 3 months post treatment (71.63±9.14; t=5.02, P=0.001). After targeted treatment, 10 patients were with skin toxicity, 8 patients were with hypertension, 8 patients were with weight loss, 7 patients were with diarrhea, 6 patients were with fatigue, 5 patients were with hepatic dysfunction, 2 patients were with proteinuria, 2 patients were with muscle pain and 1 patient was with oral ulcer. Of 19 patients, 17 insisted on continuing treatment, and the other two stopped treatment. The Tg levels at 1, 3 and 6 months post treatment were 56.26(44.60, 210.50), 53.36(41.25, 203.07) and 54.35(34.71, 223.52) mg/L, respectively, which were lower than the level prior treatment with no significant difference (110.16(49.63, 294.50) mg/L; H=2.42, P=0.490). After 3 months of targeted treatment, the progression-free survival (PFS) rate was 16/17, including 7 patients with partial response (PR), 9 patients with stable disease (SD), and 1 patient with progression of disease (PD). After 6 months of targeted treatment, the PFS rate was 10/17, including 5 patients with PR, 5 patients with SD, and 7 patients with PD. Conclusion:After 3-6 months of targeted treatment, the tumor markers of most patients are decreased with metastases improved, but the adverse events of targeted drugs have a great impact on quality of life in patients with RAIR-DTC.
ABSTRACT
Objective:To investigate the therapeutic effect of levo-thyroxine ( L-T 4) gel on hypothyroidism in rat model. Methods:A total of 30 Wistar rats (15 males, 15 females, 2-month age) were completely randomized into 6 groups ( n=5 per group) with one group as the normal control and the other 5 groups were established as the hypothyroidism models by intraperitoneal injection of 18.5 MBq 131I. Of the 5 hypothyroidism groups, 3 groups were given 0.2 g (high-dose group), 0.1 g (medium-dose group) and 0.05 g (low-dose group) L-T 4 gel per 100 g body mass on alternate days, respectively, one group was given 0.1 g blank gel per 100 g body mass daily and the other group was given 5 μg levo-thyroxine sodium tablets (Euthyrox) per 100 g body mass daily. The levels of total thyroxine (TT 4), free triiodothyronine (FT 3), free thyroxine (FT 4) and thyroid stimulating hormone (TSH) in serum were determined by radioimmunoassay and chemiluminescence immunoassay at 2, 4 and 8 weeks after administration, respectively. One-way analysis of variance and Bonferroni test were used for data analysis. Results:At 2 weeks after administration, compared with the normal control group, TT 4, FT 4 decreased and TSH increased in the oral Euthyrox group (TT 4: (65.04±8.20) vs (40.34±1.41) nmol/L, FT 4: (29.63±4.03) vs (18.03±2.76) pmol/L, TSH: (6.04±0.80) vs (10.07±1.01) mU/L; F values: 60.081-108.128, t values: from -4.44 to 4.86, all P<0.05). However, TT 4 ((67.88±14.27) nmol/L), FT 3 ((4.04±0.84) vs (4.45±0.34) pmol/L), FT 4 ((33.76±7.71) pmol/L) and TSH ((8.20±0.40) mU/L) in the L-T 4 gel low-dose group showed no significant differences with the normal control group ( t values: 0.44-2.61, all P>0.05). At 4 weeks after administration, there were no significant differences of TT 4, FT 3, FT 4 and TSH between the L-T 4 gel low-dose group/the oral Euthyrox group and the normal control group ( F values: 34.527-90.976, t values: from -0.95 to 0.35, all P>0.05). The differences of TT 4, FT 3, FT 4 and TSH were not significant between the L-T 4 gel low-dose group and the oral Euthyrox group ( t values: from -0.71 to 1.03, all P>0.05), which was still not significantly different at 8 weeks ( F values: 47.239-160.679, t values: from -0.58 to 1.02, all P>0.05). Conclusions:L-T 4 gel has obvious therapeutic effect on hypothyroidism in rats. Its effect is fast and stable, and its therapeutic effect is better than L-T 4 sodium tablets (Euthyrox).
ABSTRACT
Objective:To investigate the prognostic factors of differentiated thyroid cancer (DTC) patients with positive thyroglobulin antibody (TgAb) and varying ages after operation and 131I treatment. To explore the value of TgAb level and its change in the prognosis of DTC patients. Methods:Clinical data of 131 TgAb positive DTC patients were retrospectively analyzed. According to age, they were divided into young group(age<55 years, n=95) and elder group (age≥55 years, n=36). According to response, it was divided into excellent response group (110 cases) and non-excellent response group (21 cases). χ2 test and t test were used to compare the clinicopathological features between excellent response group and non-excellent response group. By logistic regression analysis, the independent risk factors affecting the prognosis of patients were analyzed. The receiver operating characteristic curve was used to determine the TgAb value of persistent or recurrent DTC, and the Kaplan-Meier regression curve was used to analyze the time of TgAb becoming negative. P<0.05 was statistically significant. Results:In young patients, the higher serum TgAb level before 131I treatment and the lateral lymph node metastasis were the independent influencing factors of poor prognosis [ OR=0.89(95% CI 0.83-0.95), OR=0.15(95% CI 0.05-0.52); both P<0.05]. In elder group, extraglandular invasion and higher serum TgAb before 131I treatment were associated with poorer prognosis [ OR=0.05(95% CI 0-0.83), OR=0.91(95% CI 0.76-1.13); P<0.05]. The serum TgAb thresholds for predicting DTC persistence/recurrence were 315.5 IU/mL(246.0 IU/mL in the young group and 516.5 IU/mL in the elder group). The mean time TgAb sera turned negative was (26.37±2.22) months [(23.28±2.37) months for young group and (32.64±4.07) months for elder group]. The TgAb decreased >50% in one year of the patients who had a lower probability of disease persistence/recurrence than the group without ( P<0.05). Conclusions:The high level of serum TgAb before 131I treatment and lateral lymph node metastasis were independent factors of poor prognosis in young patients, while in elder patients, extraglandular tumor invasion and the high level of serum TgAb before 131I treatment were independent factors of poor prognosis. The rate of TgAb change one year after treatment may be used as an early marker for predicting the disease status of TgAb positive patients.
ABSTRACT
Objective To analyze the pollution characteristics of 12 kinds of metals and metalloid elements in PM2.5 in Xi'an city, and to assess the health risks. Methods In 2018, PM2.5 samples were collected regularly every month at two monitoring points in Lianhu District and Yanta District of Xi'an City. The content of twelve metal and metalloid elements (Sb, Al, As, Be, Cd, Cr, Hg, Pb, Mn, Ni, Se, and Ti) in the samples were determined. The test results were statistically analyzed and evaluated according to different regions and seasons. The health risk assessment model recommended by the US Environmental Protection Agency (EPA) was used to assess the health risks of the metal and metalloid elements. Results A total of 165 PM2.5 samples were collected and analyzed. The qualified rates of As and Cd were 51.52% and 83.03%, respectively, and there was no significant difference between regions (P＞0.05). The qualified rate of As in each season from high to low was summer> autumn> winter> spring. The average concentration of As was 8.21 ng/m3, being 1.37 times higher than the standard. The average concentration of As in each season exceeded the standard, and the order from high to low was winter> spring> autumn> summer. The average concentrations of other elements did not exceed the standard. HQ value and HI value of As, Cd, Cr, Pb, Mn, Ni, Hg, Ti and Se were all less than 1. The ILCR value of carcinogenic elements As, Cd, Cr and Ni was between 3.63×10-07 ~2.58×10-05. The ILCR value was highest for As, followed by Cr. The ILCR value was highest in winter, followed by spring and autumn, and lowest in summer. The order of ILCR value was adult males> adult females> children and adolescents. Conclusion The pollution of metal and metalloid elements in the atmospheric PM2.5 in Xi'an in the winter is most serious. Arsenic and chromium in PM2.5 pose a higher potential health risk to the population through the respiratory route.
ABSTRACT
Objective:To explore the impact of urinary iodine concentration (UIC) on response to 131I treatment in differentiated thyroid cancer (DTC) patients with different risk stratifications. Methods:A total of 181 patients with DTC (75 males, 106 females, age: (44.1±12.5) years), who received the first 131I treatment in Tianjin Medical University General Hospital between January 2018 and February 2019, were retrospectively analyzed. Patients were divided into low- to intermediate-risk and high-risk groups. The treatment response was categorized into excellent response (ER) and non-excellent response (non-ER). Factors being evaluated including age, sex, preablative stimulated thyroglobulin (ps-Tg), UIC, etc. Mann-Whitney U test, χ2 test and logistic regression analysis were used for data analysis. Results:The UIC and ps-Tg in the low- to intermediate-risk group ( n=113) was 111.60(55.80, 204.65) μg/L and 2.08(0.63, 4.91) μg/L, respectively. Compared with the ER subgroup ( n=86), non-ER subgroup ( n=27) had higher UIC and ps-Tg level ( z values: -2.585, -4.511, both P<0.05). In the high-risk group ( n=68), UIC was 115.40(61.23, 167.28) μg/L and ps-Tg was 16.65(4.52, 43.45) μg/L. Compared with the ER subgroup ( n=20), non-ER subgroup ( n=48) had higher ps-Tg level ( z=-4.677, P<0.01), while the UIC was not significantly different between ER and non-ER subgroups ( z=-0.013, P>0.05). The multivariate logistic analysis indicated the ps-Tg level was the significant variable for non-ER in low- to intermediate-risk group (odds ratio( OR)=6.157(95% CI: 1.046-36.227); OR=22.965(95% CI: 3.591-146.857), both P<0.05) and high-risk group ( OR=9.696 (95% CI: 1.379-68.169), P<0.05); a high UIC could be an indicator of non-ER only in the low- to intermediate-risk group ( OR=3.715(95% CI: 1.201-11.488), P<0.05). Conclusions:The non-ER is associated with UIC in the low- to intermediate-risk group; however, UIC does not affect the non-ER in the high-risk group. Higher ps-Tg level is associated with non-ER in patients with low- to intermediate-risk and high-risk DTC.
ABSTRACT
As one of the non-invasive imaging techniques, myocardial perfusion imaging provides a basis for the diagnosis of myocardial ischemia in coronary heart disease. Aiming at the bull-eye image in myocardial perfusion imaging, this paper proposed a branching structure, which included multi-layer transposed convolution up-sampling concatenate module and four-channel weighted channels attention module, and the output results of the branch structure were fused with the output results of trunk U-Net, to achieve accurate segmentation of the cardiac ischemia missing degree in myocardial perfusion bull-eye image. The experimental results show that the multi-layer transposed convolution up-sampling concatenate module realizes the fusion of different depth feature maps, and effectively reduces the interference of the severe sparse degree which is similar to the missing degree on the segmentation. Four-channel weighted attention module can further improve the ability to distinguish between the two similar degrees and the ability to learn edge details of the targets, and retain more abundant edge details features. The experimental data came from Tianjin Medical University General Hospital, Tianjin TEDA Hospital, Tianjin First Central Hospital and Third Central Hospital. The Jaccard scores in the self-built dataset was 5.00% higher than that of U-Net. The model presented in this paper is superior to other optimized models based on U-Net, and the subjective evaluation meets the accuracy requirements for clinical diagnosis.
Subject(s)
Humans , Image Processing, Computer-Assisted , Ischemia , Myocardial Ischemia/diagnostic imaging , Neural Networks, Computer , PerfusionABSTRACT
Objective:To investigate the clinical features of patients with recurrent or metastatic differentiated thyroid carcinoma(DTC)after 131I therapy. Methods:From December 2000 to December 2017, a total of 40 patients[14 males amd 26 females, median age 48(29-60)years] with recurrent or metastatic DTC after 131I therapy in Tianjin Medical University General Hospital were reviewed. We analyzed the clinical pathological features of the patients receiving the initial 131I ablation to screen the relevant factors affecting the time of recurrence or metastasis, the dynamic serological changes, imaging characteristics and the iodine uptake in the lesion at diagnosis. Chi- square test, Mann- Whitney U test and Kaplan- Meier analysis were used to compare the differences between the two groups. Results:The time of recurrence or metastasis of DTC after 131I therapy was not statistically different in the patient′s age, gender, multifocal cancer, lymph node metastasis, the interval between the initial 131I therapy and the operation, stimulated thyroglobulin(Tg)levels before the initial ablation and last 131I therapy, and times of 131I therapy( P > 0.05), but associated with the T-stage of in-situ tumor, soft tissue metastasis and initial therapeutic dose of 131I. Patients with the T4-stage of in-situ tumor( P=0.033), soft tissue metastasis( P=0.008)and tumor initial dose≤3.7 GBq( P=0.002)were more prone to early recurrence or metastasis. From termination of 131I therapy to the diagnosis of tumor recurrence or metastasis, Tg [Tg antibodys(TgAb)negative] and TgAb(TgAb positive)showed a gradually increasing trend. Recurrent or metastatic lesions were mostly located in the cervical lymph nodes, and most of them were multiple. Among the 40 patients with recurrent or metastatic DTC, only 3 patients had iodine-avid lesions. Conclusion:The T-stage of in-situ tumor, soft tissue metastasis and initial therapeutic dose of radioiodine are important factors affecting the time of recurrence or metastasis after 131I therapy in DTC patients. Most of the recurrent or metastatic lesions don′t ever concentrate radioiodine, so it′s difficult to benefit from continued 131I therapy.
ABSTRACT
Anti-thyroid drug (ATD), radioactive iodine (RAI) and thyroidectomy are treatment options for Graves disease (GD). Treatment strategies for Graves ophthalmopathy (GO) patients include thyroid function control, oral or intravenous corticosteroids, orbital radiotherapy or orbital decompression surgery. However, current treatments for GD and GO are also less ideal because they target the signs and symptoms rather than the pathogenic mechanisms. The development of treatment strategies that targeting the thyroid-stimulating hormone receptor (TSHR) or insulin-like growth factor 1 receptor (IGF-1R) alone or in combination may yield effective and better tolerated treatments for GD and GO. This paper reviews the progress and limitations of the 2 methods.
ABSTRACT
Objective@#To compare the ablation efficacy and therapy response with 1.1 GBq and 3.7 GBq 131I in postoperative patients with low- and intermediate-risk differentiated thyroid carcinoma(DTC).@*Methods@#A total of 190 patients (43 males, 147 females, age: (45.8±11.1)years) were enrolled from July 2016 to July 2017. Among them, 96 patients received 1.1 GBq 131I and 94 were given 3.7 GBq 131I. Diagnostic whole-body scan was performed 6 months after 131I ablation for treatment response evaluation, and the successful rate of 131I ablation was calculated. χ2 test or Fisher′s exact test was used for data analysis. The cut-off value of 99Tcm-pertechnetate uptake for predicting the successful rate of remnant thyroid ablation in 1.1 GBq group was determined by receiver operating characteristic (ROC) curve analysis.@*Results@#The successful ablation rates in 1.1 GBq and 3.7 GBq groups were 79.2%(76/96) and 81.9%(77/94), respectively (χ2=0.229, P>0.05). There was no significant difference in the therapy response between the two groups (χ2=1.371, P>0.05). The successful ablation rate in 3.7 GBq group was higher than that in 1.1 GBq group for patients with stage Ⅲ (5/6 vs 1/7, P=0.029). Moreover, for patients with 5 μg/L<preablative-stimulated thyroglobulin (ps-Tg)≤10 μg/L, the ablation rate in 1.1 GBq group was lower than that in 3.7 GBq group (3/11 vs 10/13, P=0.038). ROC curve analysis showed the cut-off value of 99Tcm-pertechnetate uptake for prediction of the successful ablation rate in 1.1 GBq group was 0.061 5.@*Conclusion@#The low- and intermediate-risk DTC patients with stage Ⅲ disease, 5 μg/L<ps-Tg≤10 μg/L or higher 99Tcm-pertechnetate uptake of remnant thyroid should be given 3.7 GBq other than 1.1 GBq 131I to obtain a better ablation efficacy.
ABSTRACT
Objective To construct a model of Graves'disease ( GD ) with ( or ) Graves'ophthalmopathy ( GO) in BALB/c mice by immunization with pcDNA3. 1/TSHR289. Methods pcDNA3. 1/TSHR289 was injected into the bilateral gastrocnemius muscle of 35 model mice and electroporation was immediately performed. 10 control mice were injected with sterile saline and electroporated, while 5 blank mice were injected with sterile saline only. Each group of mice was immunized at 1, 4, 7, and 10 weeks, respectively. Serum total T4 , TSH, TSAb, and TSBAb were measured before immunization, 2 weeks after each immunization, as well as 5 and 8 weeks after the last immunization. CT scan was used to evaluate the morphological changes of the eyes of the mice.99m TcO4- imaging was used to measure the thyroid uptake function, and the pathological changes of the thyroid and orbital tissues were evaluated by HE staining. Results After the 2nd time immunization, the serum concentrations of TT4 , TSAb and TSBAb in GD mice were significantly higher than those of control and blank groups( F=13.781, 31.435, 36.112, P<0.01, respectively).The TSH continued to be significantly lower than that of control and blank groups(F=13.966, P<0.01) . After the 4th time immunizations, the ability of uptaking99m TcO4- in GD mice thyroid was significantly enhanced compared with the control group. The thyroid goiter with a large amount of lymphocyte infiltration, and the thyroid follicle was thin. CT scan of GO mice showed thickening and swelling of the extraocular muscles, and no abnormalities in tendon and muscle attachment points. HE staining showed thickening of extraocular muscle fibers, lymphocyte infiltration of extraocular muscles and orbital tissue, increased hyaluronic acid, and infiltration of fat cells. Conclusion GD or GO model can be successfully induced by multiple intramuscular injection of pcDNA3.1/TSHR289 in BALB/c mice.
ABSTRACT
Objective To compare the ablation efficacy and therapy response with 1. 1 GBq and 3. 7 GBq 131I in postoperative patients with low- and intermediate-risk differentiated thyroid carcinoma (DTC). Methods A total of 190 patients (43 males, 147 females, age:(45.8±11.1)years) were enrolled from July 2016 to July 2017. Among them, 96 patients received 1.1 GBq 131I and 94 were given 3.7 GBq 131I. Diagnostic whole-body scan was performed 6 months after 131 I ablation for treatment response evaluation, and the successful rate of 131I ablation was calculated. χ2 test or Fisher's exact test was used for data analysis. The cut-off value of 99 Tcm-pertechnetate uptake for predicting the successful rate of remnant thyroid ablation in 1.1 GBq group was determined by receiver operating characteristic ( ROC) curve analysis. Results The successful ablation rates in 1.1 GBq and 3.7 GBq groups were 79.2％(76/96) and 81.9％(77/94), respec-tively (χ2=0.229, P>0.05). There was no significant difference in the therapy response between the two groups (χ2=1.371, P>0.05) . The successful ablation rate in 3.7 GBq group was higher than that in 1.1 GBq group for patients with stageⅢ(5/6 vs 1/7, P=0.029). Moreover, for patients with 5μg/L<preablative-stimula-ted thyroglobulin (ps-Tg)≤10μg/L, the ablation rate in 1.1 GBq group was lower than that in 3. 7 GBq group ( 3/11 vs 10/13, P=0.038) . ROC curve analysis showed the cut-off value of 99 Tcm-pertechnetate uptake for prediction of the successful ablation rate in 1.1 GBq group was 0. 0615. Conclusion The low- and inter-mediate-risk DTC patients with stageⅢdisease, 5μg/L<ps-Tg≤10μg/L or higher 99 Tcm-pertechnetate up-take of remnant thyroid should be given 3.7 GBq other than 1.1 GBq 131I to obtain a better ablation efficacy.
ABSTRACT
Objective To investigate the predicative value of midkine (MK) as a cancer biomarker for metastatic lesions in differentiated thyroid cancer (DTC) patients with positive thyroglobulin antibodies (TgAb) before the first 131Ⅰ therapy.Methods MK levels were measured by enzyme-linked immunosorbent assay in 151 recruited DTC patients included in this study according to strict inclusion and exclusion criteria.There were 28 TgAb positive DTC patients with metastases and 123 DTC patients without metastases.The value of pre-131Ⅰ-ablative MK to predict metastasis was assessed by receiver operating characteristic (ROC) curves in these two groups of patients.Results MK levels were significantly higher in TgAb positive DTC patients than those in DTC patients without metastases.MK levels showed good diagnostic value,with an area under the curve of 0.856 (P＜0.001),and a diagnostic accuracy of 83％ at the optimal cut-off value of 550 ng/L.Conclusion Results show that MK can potentially be used as a surrogate biomarker for predicting DTC metastases when thyroglobulin is not suitable due to TgAb positivity.
ABSTRACT
Objective Midkine ( MK ) and nuclear factor-kappa B ( NF-kB ) play pivotal roles in tumorigenesis, which are considered as promising cancer biomarkers. The efficacy of MK and NF-kB as markers for diagnosis and prediction of synchronous metastasis in papillary thyroid cancer ( PTC ) was the aim of present investigation. Methods Seventy six cases of PTC and seventy cases of multi-nodular goiter ( MNG ) were retrieved. The PTC group was further divided into subgroup 1 (16 cases with synchronous metastasis) and subgroup 2 (60 cases without metastases). A retrospective review of clinical information, radiological examinations,131 I treatments and post-131 I-therapy scans were done. Immunohistochemistry of MK, NF-kB p65, and Ki-67 was performed on paraffin-embedded specimens and results were quantified. Diagnostic values of the parameters were conducted by receiver operating characteristic (ROC) curves. Diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were determined. Protein levels of MK and NF-kB p65 were then confirmed by Western blot. Results Immunoreactivities of MK and NF-kB p65, and positive percentage of Ki-67 were significantly higher in PTC group than in MNG group (all P<0. 01). ROC showed good differential diagnostic capabilities of all three parameters with diagnostic accuracies of 82. 192% , 80. 137% , and 84. 091%respectively. Moreover, all three parameters were significantly higher in subgroup 1 than those in subgroup 2 (all P<0. 01). ROC showed good predicting efficacies in synchronous metastasis of all three parameters with diagnostic accuracies of 82. 895% , 80. 263% , and 76. 316% respectively. By one-way analysis of variance, Western blot showed that MK and NF-kB p65 protein levels in lesions from subgroup 1 were significantly higher than those from subgroup 2, both were significantly higher than those in MNG lesions ( P<0. 01). Conclusion MK and NF-kB immunohistochemistry can potentially be used for differential diagnosis between PTC and MNG, and for prediction of synchronous metastases.
ABSTRACT
Objective Liver dysfunction is a common complication of hyperthyroidism [ mainly Graves’ disease(GD)], that may restrict the choice as well as affect the ultimate outcome of treatment. The purpose of this study was to describe the clinical and biochemical patterns in patients suffering from Graves’ disease and liver dysfunction and to determine influential factors. Methods A total of 1 928 patients received radioactive iodine, 131 I treatment. Before 131 I therapy, 24 h radioactive iodine uptake of thyroid(24 h RAIU), serum free triiodothyronine (FT3 ), free thyroxine( FT4 ), sensitive thyroid-stimulating hormone( sTSH), anti-thyrotrophin receptor antibody (TRAb), thyroglobulin antibody(TgAb), anti-thyroid peroxidase antibody(TPOAb), and serum hepatic function parameters etc were performed. Data were analyzed by the unpaired t-test, the independent samples t-test, the χ2 test, logistic regression, and Pearson bivariate correlation. Results Ages, the course of Graves’ disease, the weight of thyroid, FT4 , TPOAb, and TRAb in Graves’ disease patients complicated with liver dysfunction were higher than those in patients with normal hepatic function, as shown in table 1. The influential factors including age, course of Graves’ disease, heart rate, weight of thyroid, FT4, 24 h RAIU, TgAb, TPOAb, and TRAb. 24 h RAIU were the protecting factors. Age, course of Graves’ disease, heart rate, weight of thyroid, FT4 , TRAb, and TPOAb were the risk factors. Conclusion The risk of liver dysfunction in patients with Graves’ disease was increased in the following cases: age over 45 years, heart rate above 90 bpm, weight of thyroid more than 35 g, course of Graves’ disease longer than 3 years, FT4 greater than 70. 5 pmol/ L, TPOAb above 360 IU/ ml, and TRAb above 15 IU/ L. In these coses 131 I therapy will be recommended.
ABSTRACT
The incidence rate of thyroid cancer is increasing very rapidly during the past years.131I treatment for DTC is an effective method.However,DTC refractory to 131I treatment or therapeutic failure is not uncommon.High level expression of nuclear factor-kappa B (NF-λB) in thyroid cancer is closely related with carcinogenesis,progression,anti-apoptosis and therapeutic resistance.NF-κB inhibitor was effective for the treatment of thyroid cancer.Combined NF-κB inhibitor with131I may improve the therapeutic efficacy.
ABSTRACT
Objective To study the effect of nuclear factor-kappa B (NF-κB) inhibition by small interference RNA (siRNA) on the apoptosis of DTC cells treated by 131 I.Methods DNA binding assay was performed at 24 h after 131I treatment (2 × 104 MBq/L) on KTC-1 cells.The cell survival assay was conducted at 48 h after 131 I treatment.Western blot was used to detect the changes of NF-κB p65 at 6 h after 131I treatment,and the changes of anti-apoptotic factors and apoptotic key factors at 24 h after 131 I treatment.The anti-apoptotic factors included in this study were X chromosome-linked inhibitor of apoptosis (XIAP),cellular inhibitor of apoptosis 1 (cIAP1) and B-cell lymphoma extra large (Bcl-xL),and the apoptotic key factors were caspase 3 and poly-ADP-ribose polymerase (PARP).A total of 4 groups were studied for the detection of p65 and anti-apoptotic factors by Western blot:no oligonucleotide transfection control group (A),no oligonucleotide transfection + 131I group (B),scrambled oligonucleotides transfection + 131I group (C) and p65 siRNA transfection + 131I group (D).Another 6 groups of studies were:oligonucleotide transfection control group (1),scrambled oligonucleotides transfection group (2),p65 siRNA transfection group (3),no oligonueleotide transfection + 131I group (4),scrambled oligonucleotides transfection +131I group (5) and p65 siRNA transfection + 131I group (6).One-way analysis of variance and q test were performed for statistical analysis.Results The results of DNA binding assays for the 6 groups (1,2,3,4,5,6) were (100.00 ± 11.65)％,(96.00 ± 17.98)％,(9.28 ±5.01)％,(322.72 ±50.81)％,(311.36 ±44.81)％ and (36.96 ± 15.66)％,respectively (F =137.74,P ＜0.01).NF-κB functions were strengthened with 131 I treatment (qgrouo 4∶1 =10.90,qroup 5∶2 =11.38,both P ＜ 0.01).However,NF-κB p65 siRNA transfection could inhibit NF-κB functions (qgroup1∶3 =18.25,qgroup4∶6 =13.71,both P ＜0.01).Cell survival rates of the 6 groups were (100.00 ± 11.65)％,(96.32 ± 9.44)％,(70.88 ±7.41)％,(64.16 ±9.50)％,(62.24 ±9.37)％ and (28.64 ±6.74)％ (F=52.76,P＜0.01).There were significant differences between groups 3 and 6,groups 4 and 6 (q =10.76 and 7.79,both P ＜ 0.01).Western blot results showed that the expression of NF-κB p65 in the 4 groups (A,B,C,D) were (56.60 ±7.37)％,(111.07 ± 13.31)％,(113.16± 15.04)％ and (12.46 ±2.74)％,respectively (F=60.17,P ＜ 0.01).The t65 levels increased with 131 I treatment (qgroup B∶A =6.20,qroup c∶ A =5.85,both P ＜0.01); while decreased significantly using NF-κB p65 siRNA transfection (qgroup B:D =-12.57; qgroupC∶D =11.41,both P ＜ 0.01).Western blot results showed that XIAP,cIAP1 and Bcl-xL in the 4 groups were (17.59±1.96)％,(16.45± 1.85)％ and (19.92 ±2.22)％; (98.37± 17.92)％,(109.81 ±19.16)％ and (95.59 ±22.20)％ ; (98.43 ±18.71)％,(98.86± 15.88)％ and (100.99 ±21.70)％ ;(7.00 ± 0.95) ％,(5.86 ± 0.35) ％ and (9.52 ± 0.90) ％,respectively (F =44.22,56.51 and 29.11,all P ＜ 0.01).131 I treatment induced higher expression of all the 3 genes (qgroup B∶ A =7.76,8.40 and 5.88,all P ＜0.01),while NF-κB p65 siRNA transfection,on the contrary,reduced the expression of all the 3 genes (qgroupB:D =8.82,9.40 and 6.71,all P ＜0.01).There were significant differences of p19,p17,p116 and p89 in the 6 groups(F =39.03,48.45,32.56,52.20,all P ＜ 0.01),especially among group 3,4 and 6 (q =3.18-9.98,all P ＜ 0.05).Conclusions 131I could activate NF-κB function and enhance the expressions of anti-apoptotic factors.NF-κB p65 siRNA transfection could effectively suppress this effect and therefore magnify 131I induced apoptosis in DTC cells.