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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.
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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.
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Objective:To investigate the correlation between 131I uptake and therapeutic efficacy in metastatic differentiated thyroid carcinoma (DTC). Methods:The clinical data of 138 patients with metastatic DTC (42 males, 96 females, age range: 8-74 years) treated with 131I in nuclear medicine departments of 31 centers all over China were retrospectively analyzed. The lesional 131I uptake was quantitatively analyzed with target-to-nontarget (T/NT) ratio through the regions of interest in metastatic lesions confirmed by either planar or tomographic 131I SPECT/CT imaging. The efficacies of 131I treatment on the metastatic DTC were divided into complete remission (CR), partial remission (PR), stable disease (SD) and progress disease (PD) based on the change of the lesion diameter before and after the treatment. Factors which may affect therapeutic efficacy were assessed by the univariate (Kruskal-Wallis rank sum test, χ2 test and one-way analysis of variance) and binary logistic regression analyses. The receiver operating characteristic (ROC) curve of lesional T/NT ratio to predict the ineffectiveness of 131I therapy was performed. Results:A total of 1 165 efficacies were evaluated. The planar imaging results ( n=653) showed that there was no statistically significant difference of T/NT ratio among CR, PR, SD and PD groups ( χ2=4.15, P>0.05). The tomographic imaging results ( n=512) suggested CR, PR, SD and PD in 7.6%(39/512), 65.8%(337/512), 22.9%(117/512), and 3.7%(19/512) of individuals, respectively, and the T/NT ratio among the four groups was significantly different ( χ2=30.46, P<0.01). The univariate analysis also showed that age, stimulated thyroglobulin(sTg), 131I dose were the factors affecting therapeutic efficacy ( F or χ2 values: 2.561, 7.095 and 8.799, all P<0.05). Furthermore, binary logistic regression analysis revealed that older patients (odds ratio ( OR)=1.034, P=0.022) or patients with lower lesional T/NT ( OR=1.086, P=0.006) had a higher probability of ineffectiveness. The area under ROC curve for T/NT ratio to predict ineffectiveness was 0.726, and the cut-off value was 6.2, with a sensitivity of 78.7%(107/136) and a specificity of 73.1%(275/376). Conclusions:131I therapy is an effective treatment for metastatic DTC. The age at the time of metastatic diagnosis and the lesional T/NT ratio are independent influential factors for ineffectiveness of 131I therapy. When the leisonal T/NT ratio is lower than 6.2, the inefficiency of 131I is higher.
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Objective To investigate the influence of different time discontinuation of compound iodine solution on 131Ⅰ uptake and curative effect of 131Ⅰ therapy in patients with Graves disease (GD).Methods A total of 1 585 patients (415 males,1 170 females;age range:17-62 years) treated with 131Ⅰ therapy for the first time between January 2012 and November 2016 were enrolled in this retrospective study.All patients were divided into preliminary treatment group (n =85) and control group (no iodine solution taking,n =1 500).Preliminary treatment group including 4-7 d discontinuation subgroup (group A,n=35),8-14 d discontinuation subgroup (group B,n=28) and 15-30 d discontinuation subgroup (group C,n=22).The high-est radioactive iodine uptake (RAIU),effective half-life,free triiodothyronine (FT3) and free thyroxine (FT4) levels before 131Ⅰ therapy were compared,and curative effects were evaluated.One-way analysis of variance,Ridit analysis and x2 test were used to analyze the data.Results The highest RAIU in group A,group B,group C and control group was (64.86 ± 13.20) ％,(67.40 ± 9.10) ％,(73.46 ± 4.65) ％ and (74.14±9.87) ％,respectively (F =1.658,P＞ 0.05).No significant difference was found in the effective half-life among 4 groups (F=0.651,P＞0.05).FT3 level in group A and group B ((11.90±4.85) and (15.51±2.95) pmol/L) was significantly lower than that in control group ((23.98±4.98) pmoL/L) and group C ((22.08±2.31) pmol/L;F=13.972,t values:6.57-12.08,all P＜0.05).FT4 level in group A and group B ((25.65±11.95) and (32.33±6.25) pmol/L) was obviously lower than that in control group ((73.65±21.55) pmol/L) and group C ((68.41±13.94) pmo]/L;F=21.238,t values:36.09-48.00,all P＜0.01).The overall curative effect of preliminary treatment group and that of control group were not statistically significant (u=0.397,P＞0.05),and no significant difference was found in the complete remission rates among 4 groups (x2 =1.169,P＞0.05).Conclusions If pretreatment with compound iodine solution is used before 131Ⅰ therapy in GD,it is feasible to carry out 131Ⅰ therapy within 2 weeks after withdrawal.In order to avoid the possibility of severe hyperthyroidism after 131Ⅰ therapy,it is recommended that radioiodine treatment should be carried out after discontinuation for 4-7 d.
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Objective To investigate the radioactivity distribution of 131 I-bovine serum albumin ( BSA )-mesoporous silica nanoparticles ( MSNs )-anti-vascular endothelial growth factor receptor 2 (VEGFR2) in anaplastic thyroid carcinoma (ATC) and to explore its antitumor efficacy in ATC-bearing nude mouse models. Methods 131 I-BSA-MSNs-anti-VEGFR2 and 131 I-BSA-MSNs were constructed. FRO tumor xenografts were established and the SPECT/CT images of tumor-bearing mice were acquired at differ-ent time points after intratumoral injection with 131 I-BSA-MSNs-anti-VEGFR2 ( targeting group) , 131 I-BSA-MSNs ( non-targeting group) , Na131 I ( Na131 I group) and saline ( control group) , respectively. The changes of body mass and tumor volume in each group were recorded. Two-sample t test and log-rank test were used to analyze the data. Results After incubation for 3 h, the fluorescence intensity in targeting group was higher than that in non-targeting group (345.26±16.35 vs 280.61±9.65;t=5.90, P<0.05). After injection for 1-3 weeks, the radioactivity detected by SPECT/CT in targeting group was obviously stronger than that in non-targeting group ( t values:7.060-12.780, all P<0.05) . At the end of the observation, the tumor vol-ume of Na131I group, control group, non-targeting group and targeting group increased to (278.3±19.3)％, (296.6±24.2)％, (198.7±13.2)％ and (103.7±6.2)％ of the original volume, respectively. The body mass of the first 2 groups decreased to (88.6±3.0)％ and (86.2±3.1)％ of the original body mass respec-tively, while that of the latter 2 groups increased to (102.1±3.1)％ and (116.2±3.4)％ of the original body mass respectively. Survival analysis showed that the median survival time in targeting group ( 38 d) was sig-nificantly longer than that in non-targeting group (34 d;χ2=8.05, P<0.05). Conclusion 131I-BSA-MSNs-anti-VEGFR2 can effectively inhibit the tumor growth of ATC and prolong the survival of tumor-bearing nude mice, which gives a good suggestion for the treatment and prognosis evaluation of ATC.
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Objective To investigate the effects of gastrodin on neural function and the expression of myelin basic protein (MBP) and neurofilament high molecular weight (NFH) in the striatum during cerebral ischemiareperfusion in mice.Methods 36 Kunming mice were randomly divided into sham group,MCAO group and gastrodin (GAS) group.The middle cerebral artery occlusion(MCAO) was established by artery embolization.The mice in sham group were received fake surgery and saline,and the mice in MCAO and GAS group were exposed to MCAO,and received saline and GAS (100 mg/(kg · d)) injection,respectively,immediately after the operation for 7 days.On the 8th day of operation,the neurological severity scores of the mice were observed and the volume ratio of the cerebral infarction was estimated by triphenyl tetrazolium chloride (TTC) staining.Immunohistochemistry was used to detect the MBP and NF-H in the striatum.Results (1) The mice in MCAO group showed significant neurologic deficient in comparison with sham group,and the neurological severity scores of gastrodin group(3.13±0.64) were significantly higher than that(1.38±0.52) of MCAO group (P＜0.05).(2) Results of TTC staining showed that the infarction volume was obviously larger in the injured cerebral tissue in MCAO group in comparison with sham group,and the volume ratio of the cerebral infarction significantly decreased after the intervention with GAS (P＜0.05).(3) The integral optical density of MBP(272968.14±1215.23) and NF-H(12 142.73±47.16) in MCAO group decreased as compared to that((43 855.23±2434.16),(275 321.00±926.15)) in sham group and GAS group((321 531.2±2376.14),(106 135.73±598.15)) (P＜0.05).Conclusion GAS can improve neural function of mice after middle cerebral artery occlusion,and it may play an important role in protecting myelin and nerve fibers of striatum.
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Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the depressive like behaviors and expression of brain derived neurotrophic factor (BDNF),IL-1β and NF-κB of hippocampal in chronic unpredictable mild stress (CUMS) rats.Methods Thirty-two adult male rats were randomly divided into four groups (n =8):Control group,Control + rTMS group,CUMS group and CUMS + rTMS group.The sucrose preference test,forced swim test and open field test were used to evaluate depressive like behaviors for each groups.In addition,the expression of BDNF,NF-κB and IL-1 β in hippocampal were detected by western blot and ELISA after behavioral test,respectively.Results 1.The effects of rTMS on depressive like behaviors of CUMS rats:in the sucrose preference test,the sucrose preference rate of CUMS rats (0.67 ± 0.06) was significantly lower than Control group (0.91 ± 0.04),which was higher in the CUMS + rTMS group (0.83 ±0.08).In the forced swim test,the immobility time of CUMS group ((26.88 ± 11.33) s) was longer than Control group ((15.22 ± 6.75) s) and CUMS + rTMS group ((18.41 ± 6.95) s).In the open field test,both the total distance travelled and number of central area entry times of CUMS group((849.165 ± 769.01) cm,(7.42 ± 5.68))were significantly shorter ((6224.81 ± 1403.2) cm) and smaller (22.86 ± 3.72) than Control group,and those of the CUMS + rTMS were longer ((4105.57 ± 1516.92)cm) and larger (21.25 ± 3.45).All the behavioral results were statistically significant (P＜ 0.05).And of all the aforementioned behavioral parameters,there were no significant differences between Control group and Control + rTMS group(P＞0.05).2.The effects of rTMS on the hippocampal expressions of BDNF,NF-κB and IL-1β in CUMS rats:compared with Control group,the hippocampal expression of BDNF in CUMS rats was significantly decreased,while the expressions of NF-κB and IL-1β in the hippocampus were significantly increased (P＜ 0.05).Compared with CUMS group,the hippocampa expression of BD-NF in the CUMS + rTMS group was increased,and the expressions of NF-κB and IL-1β in the hippocampus was significantly decreased (P ＜ 0.05).The expressions of BDNF,NF-κB and IL-1β had no differences between Control group and Control + rTMS group.Conclusion rTMS increased the expression of BDNF,reduced the production of NF-κB and IL-1β,and alleviated depressive like behaviors in CUMS rats.