1.Synergistic effects of nuclear factor-kappa B inhibition by small interferece RNA on 131I therapy in differentiated thyroid cancer cells
Yajing HE ; Zhaowei MENG ; Jian TAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2013;(3):207-212
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.
2.Analysis of 2125 patients with hyperthyroidism after 131I therapy: a retrospective study
Renfei WANG ; Jian TAN ; Guizhi ZHANG ; Yajing HE
Chinese Journal of Endocrinology and Metabolism 2015;31(5):421-426
Objective To analyze the efficacy of 131I therapy for Graves' disease,and to investigate the incidences of complete remission and hypothyroidism after single or multiple treatments.Methods Altogether 2 125 patients with Graves' disease (614 males,1 511 females) aged (39.8 ± 10.2) years received 131I treatment.The diagnostic and therapeutic procedures were carried out as follows:physical examination,determination of thyroid hormones and antibodies,undergoing 131I uptake test to obtain maximum of thyroid uptake value and effective half-life time,ultrasonography,thyroid imaging,calculating 131I therapeutic dosage,131I treatment,follow-up appraisal of curative effect.The data were analyzed by x2 test,optimal scale regression,logistic regression and discriminant analysis.Results The rates of complete remission,hypothyroidism,partial response,and invalid in the 2 125 cases more than half a year after 131I therapy were 54.3 %,21.3 %,20.3 %,and 4.1% respectively.In all patients the rate of clinical cure (including complete remission and hypothyroidism) and rate of effectiveness were 75.6% and 95.9% respectively.The rate of recovery and incidence of hypothyroidism in patients who accepted single 131I treatment were 52.4% and 21.2% respectively,while in patients who accepted twice or multiple 131I therapy the respective figures became 66.2% and 21.8% accordingly.The influential factors in the effectiveness of 131I treatment included age,thyroid weight,TSH receptor antibody (TRAb),and dose of 131 I per gram of thyroid.Conclusions Patients who did not achieve clinical cure for over 6 months after first 131 I treatment,may receive another131 I therapy to further improve the remission rate.Age,thyroid weight,TRAb etc,contribute to the efficacy of 131I therapy for Graves' disease.The multi-perspective and multi-factor analysis would have the benefit to establish individualized treatment strategy.
3.Correlation between external dose equivalent rate and residual radioactivity in patients with differentiated thyroid carcinoma after 131I therapy
Renfei WANG ; Jian TAN ; Guizhi ZHANG ; Yajing HE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2016;36(5):394-397
Objective To investigate the correlation between external dose equivalent rate (EDER)and residual radioactivity in DTC patients after 131I therapy.Methods A total of 70 DTC patients (15 males,55 females;average age (45.7±12.8) years) who received 131I therapy from January 2015 to May 2015 were reviewed.Patients were divided into remnant ablation group (Group 1,43 patients) and the group of therapy for persistent disease (Group 2,27 patients).The determination of dose equivalent rate at 1,2 and 3 m from the patients was performed at 1,6,18,24,30,42,48,54,66 and 72 h after the administration of 131 I.Simultaneously,the residual radioactivity was estimated through collecting their urine and monitoring the excretion of radioactivity.The correlation between EDER and residual radioactivity was analyzed.Results The functions of standard EDER (μSv · h-1 · MBq-1) at 1 m from the patients of Group 1 and Group 2 were H=0.044 77e-0.063 8t +0.015 04e-0.396t.and H=0.039 71e-0.0629t +0.014 12e-0.325t,respectively.And the functions of residual radioactivity (MBq) of the two groups were A =A0(0.84e-0.061 7t+ 0.16e-0.158 4t)and A =Ao(0.69e-0.087 7t+ 0.31e-0.047 3t),respectively.There was a positive correlation between EDER and residual radioactivity in DTC patients after the administration of 131I (r=0.95,P<0.001).The fitting function of the dose equivalent rate at 1 m from the patients was H(μSv/h)=0.048A (MBq).Conclusions The residual radioactivity in DTC patients after 131 I therapy can be estimated by determining the EDER.The dose equivalent rate at 1 m from the patients of lower than 19.2 μSv/h can be used as the limitation of radiation isolation.
4.Curative efficacy and influential factors of 131I treatment for lung metastases from differentiated thyroid carcinoma
Renfei WANG ; Jian TAN ; Guizhi ZHANG ; Wei ZHENG ; Yajing HE ; Chengxia LI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2015;35(4):258-261
Objective To investigate the efficacy and influential factors of 131I treatment for lung metastases from DTC.Methods Fifty patients (18 males,32 females;age (40.8±13.2) years) with lung metastases from DTC who underwent 131I treatment from October 2007 to December 2012 were retrospectively analyzed.The efficacy of 131 I treatment was assessed using 131I imaging and determination of serum Tg level after 6 months.The possible factors affecting efficacy included patients' age,gender,operation method,pathological classification,the diagnostic time of pulmonary metastasis,serum Tg level at diagnosis,131I uptake pattern,characteristics of other imaging modalities,cervical lymph node metastases and extrapulmonary distant metastases (assign 1 for metastases,0 for no metastases).Univariate and multivariate analyses (Student t test,Fisher exact test and logistic regression) were performed to investigate the factors.Results The rates of complete remission,partial response and invalid of 131I treatment were 20% (10/50),74% (37/50) and 26% (13/50) respectively.Univariate analysis showed that age(t =2.019,P<0.05),gender (P =0.032),serum Tg level at diagnosis (t =2.646,P< 0.05),findings of other imaging modalities (P =0.039),and extrapulmonary distant metastases(P=0.023) were the factors influencing outcome of 131I treatment.Multivariate logistic regression analysis showed that the influential factors included age,serum Tg levels and extrapulmonary distant metastases.The regression equation was as follows:logit P =2.127-0.056× age-0.163×Tg level-1.280×extrapulmonary distant metastasis (x2=10.484,P<0.001).Aged patients,a significant increase of Tg level and extrapulmonary distant metastases indicated a poor prognosis.Conclusions 131I treatment is an effective method for lung metastases from DTC.The patients with younger age,lower Tg levels,no other distant metastases had good response to 131I treatment.
5.Effect of Mindfulness-based Stress Reduction on Perceived Stress and Mental State of Patients with in Vitro Fertilization
Kai LIU ; Xianhua LIN ; Rong LI ; Yajing TAN ; Yong WANG ; Chenming XU
Progress in Modern Biomedicine 2017;17(24):4668-4671,4730
Objective:To investigate the effect of Mindfulness-based stress reduction (MBSR) on perceived stress and mental state of patients with in vitro fertilization.Methods:83 cases women who were assisted reproduction with in vitro fertilization and embryo transfer (IVF-ET) in our hospital from May 2014 to December 2016 were selected as research objects.All the subjects were divided into control group and observation group according to the random number table method,with 41 cases in the control group and 42 cases in the observation group.Patients in the control group were given routine comprehensive nursing intervention,while the observation group was given MBSR intervention on the basis of the control group.The scores of self rating depression scale (SDS),self rating anxiety scale (SAS) and Chinese perceived stress scale (CPSS) before and after the intervention in the two groups were compared.Results:There was no significant difference in SDS score,SAS score and CPSS score between the two groups before intervention (P>0.05).The scores of SDS,SAS and CPSS in observation group after intervention were (43.53± 4.89),(42.38± 4.34) and (27.53± 4.89),which were lower than (57.96± 7.30),(56.42± 5.49),(37.96± 7.30) before intervention,and the differences were statistically significant (P<0.05).The scores ofSDS,SAS and CPSS in control group after intervention were (51.13± 5.52),(51.13± 5.52) and (31.13± 5.52),which were lower than (58.83± 7.28),(56.45± 5.51),(38.83± 7.28) before intervention,and the differences were statistically significant(P<0.05).And those scores in were lower in observation group than in control group,the differences were statistically significant (P<0.05).Conclusion:MBSR intervention can effectively improve the anxiety,depression and perceived stress of patients with in vitro fertilization,which is helpful in improving the success rate of IVF-ET,and it is worthy of clinical application.
6.Association between urinary iodine concentration and radioactive iodine therapeutic response in patients with differentiated thyroid cancer
Yuyan JIANG ; Zhaowei MENG ; Jian TAN ; Ning LI ; Qiang JIA ; Renfei WANG ; Yajing HE ; Wei ZHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(4):207-211
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.
7.Clinical value of MRI in differentiation of rectal cancer T staging
Zongyuan XIE ; Zhiqiang WANG ; Zhibin TAN ; Yajing WANG ; Jingjing WANG ; Hui LI ; Tao LIU
The Journal of Practical Medicine 2017;33(8):1303-1306
Objective To investigate the application value of functional magnetic resonance imaging nethods diffusion weighted imagingand dynamic contrast-enhanced magnetic resonance imaging in theT stagingof rectal cancer.Methods Through the retrospectively analysis of DWI and DCE-MRI images of 78 rectal cancer patients confirmed by pathology,the different of routine sequence examination and functional magnetic resonance imaging combined with routine sequence examination in T thestaging diagnosis were contrasted analysis.The correlation of ADC value and quantitative parameters of Ktrans,Kep and Ve values with tumor T staging was analyzed.Results The functional magnetic resonance imaging combined with routine sequence examination in T staging screened 68 cases successfully,and the accuracy rate was 87.2%.preoperative T staging and postoperative pathology of rectal cancerwas better thanroutine sequence examinationin T staging (59 cases,with the accuracy rate 75.6%) (Kappavalue:0.81 vs 0.65,P < 0.05).The ADCvalue andDCE-MRI quantitative parameters values of K and Ve increased with the increase of tumor T staging (P < 0.05).There was no statistically significant difference of Kep values.Conclusions The ADC value and DCE-MRI quantitative parameters (K and Ve values) had certain relevance with Tstaging of rectal cancer.The functional magnetic resonance imaging had a high accuracy in the preoperative T staging of rectal cancer,which proves certain clinical value in judging invasion depth of tumor in the rectal wall.
8.Immunohistochemical evaluation of midkine and nuclear factor-kB as markers for diagnosis and prediction of synchronous metastasis in papillary thyroid cancer
Zhaowei MENG ; Jian TAN ; Yujie ZHANG ; Guizhi ZHANG ; Mingfang ZHANG ; Yajing HE ; Weijun TIAN ; Qiang JIA ; Qing HE ; Mei ZHU ; Xue LI ; Jianping ZHANG
Chinese Journal of Endocrinology and Metabolism 2015;(7):581-586
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.
9.Predictive value of the stimulated thyroglobulin before and after 131I therapy for curative effect in patients with papillary thyroid carcinoma
Lingyun XU ; Jian TAN ; Guizhi ZHANG ; Fuhai ZHANG ; Yajing HE ; Renfei WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(3):156-159
Objective To analyze the stimulated thyroglobulin (sTg) level and variation tendency before and after 131I therapy in papillary thyroid carcinoma (PTC),and evaluate the predictive value of sTg for the efficacy of 131I therapy.Methods From January 2013 to September 2016,a total of 178 PTC patients (53 males,125 females;average age (44.1±11.4) years) without distant metastases who received 131I treatment in Tianjin Medical University General Hospital were reviewed.The patients were divided into two groups:group 1 (n=23) with residual thyroid detected by 131I whole body scan (WBS) and group 2 (n=155) without residual thyroid.Both thyroid stimulating hormone (TSH) and sTg were measured and defined as TSH1,sTg1 before 131I therapy,and TSH2,sTg2 after 131I therapy.Data of the two groups were compared with two-sample t test,x2 test and Mann-Whitney u test.The receiver operating characteristic (ROC) curve and diagnostic critical point (DCP) were used to evaluate the predictive value of sTg in radioiodine ablation efficacy.Results There were no significant differences in age (t=1.007),gender (x2 =1.419),tumor diameter (u=1 385),multifocal cancer (x2 =0.371),extrathyroidal extension (x2 =0.020) or lymph node metastasis (x2=0.391,all P>0.05) between group 1 and group 2.The levels of sTg1 and sTg2 of group 1 were 6.3(2.0,16.9) and 1.7(0.8,4.2) μg/L,which were higher than those of group 2 (2.7(0.6,6.4) and 0.3(0.2,1.3) μg/L;u=1 118.5,817.0,both P<0.01).△sTg and △sTg/△TSH showed no statistical differences between the two groups (u =1 359.5,1 195.0,both P>0.05).The area under ROC curve,DCP,sensitivity,specificity,positive predictive value,and negative predictive value of sTg1 were 0.686,4.435 μg/L,60.9%(14/23),67.7%(105/155),21.9% (14/64) and 92.1%(105/144),respectively.Meanwhile,the parameters of sTg2 were 0.771,0.460 μg/L,91.3% (21/23),58.1% (90/ 155),24.4%(21/86) and 97.8%(90/92),respectively.Conclusions The level of sTg could be used to predict the efficacy of 131I therapy in PTC patients.Preablative sTg1 (<4.435 μg/L) or postablative sTg2 (< 0.460 μg/L) holds high negative predictive value in identifying the efficacy of single 131I therapy.
10.Establishment of a mesenchymal stem cells model stably expressing hCD4 and hCCR5
Yajing LI ; Fuyan ZHUGE ; Juan LIANG ; Jinyang HE ; Ning TAN ; Changchun ZENG
Chongqing Medicine 2017;46(32):4465-4468,4472
Objective To establish a kind of mesenchymal stem cells(MSCs) model that could express hCD4 and hCCR5 to study the field of human immunodeficiency virus type 1 (HIV-1).Methods Lentiviral vectors containing the genes of hCD4 and hCCR5 under the transcriptional control of cytomegalovirus promoter were designed.MSCs were transfected by the lentiviral vectors at optimum multiplicity of infection.Transduction efficiencies of hCD4 and hCCR5 in MSCs were analyzed by quantitative real-time polymerase chain reaction(RT-PCR),Western blot,and immunofluorescence staining.Subsequently,the transfected human MSCs were infected with HIV-1,and the expression of HIVRNA in the MSCs was detected by RT-PCR.Results The MSCs model con-taining hCD4 and hCCR5 and supporting normal HIV-1 infection was constructed.qRT-PCR showed that MSCs upon infection with lentiviral vectors were highly expressed in hCD4 and CCR5 mRNA sequences(P<0.01).Western blot detection showed the positive bands of 55.0 × 103 (hCD4) and 40.6 × 103 (hCCR5).The results of immunofluorescence staining revealed that hCD4 and CCR5 were expressed on the surface of MSCs.Such results were not found in cells infected with empty lentiviral vectors.And the susceptibility of the hCD4/CCR5 transgenic MSCs to the HIV-1 was further indicated by the detection of HIV-1 RNA in the culture supernatants and cell lysates(P<0.05).Conclusion The MSCs model that could highly express hCD4 and hCCR5 was established to support normal HIV-1 infection,which can be used to investigate the development of new therapies and vaccines against HIV.