Due to the specificity of radiopharmaceuticals for targeted α radionuclide therapy, such as radioactivity and radiation damage risk, it is necessary to estimate the internal radiation dose in preclinical evaluation to correctly evaluate the efficacy and safety of the drug, as well as in subsequent clinical studies. This review illustrates current research status of estimating internal radiation dose of targeted α radionuclide therapeutic radiopharmaceuticals based on preclinical studies, in order to add insights for understanding estimation of radiopharmaceuticals internal radiation dose and provide reference for the preclinical evaluation of radiopharmaceuticals.

Objective:To explore the clinicopathologic features differences between tall cell variant of papillary thyroid cancer (TCV-PTC) and PTC with tall cell features (PTC-TCF) and the factors influencing efficacy of 131I therapy in patients with TCV-PTC and PTC-TCF. Methods:A retrospective analysis was conducted on 84 patients (28 males, 56 females, age 43.5(35.0, 55.0) years) with pathologically confirmed TCV-PTC or PTC-TCF and who were treated with 131I therapy from January 2018 to June 2023 in the Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University. The patients were divided into structural incomplete response (SIR) group and non-SIR group according to 131I treatment response. Data differences were analyzed by Wilcoxon rank sum test, Fisher exact test, or Mann-Whitney U test. Variables with P<0.1 were enrolled in logistic multivariate regression analysis. The ROC curve was used to obtain the cut-off value of stimulated thyroglobulin (sTg). Results:A total of 37 patients with non-SIR and 6 patients with SIR were found in TCV-PTC group ( n=43), and 33 non-SIR and 8 SIR cases were found in PTC-TCF group ( n=41). Univariate analysis revealed that sTg differed significantly between non-SIR patients and SIR patients in TCV-PTC group ( Z=-2.81, P=0.003), while no significant differences observed for sex, age, multifocality, capsular invasion, T stage, N stage, B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF) V600E mutation, initial recurrence risk, number of metastatic lymph nodes, maximum tumor diameter ( Z values: from -0.74 to -0.11, all P>0.05). In TCV-PTC group, sTg also differed significantly between non-SIR patients and SIR patients ( Z=-4.40, P<0.001), while the other clinical factors above and the proportion of tall cells showed no significant difference ( Z values: from -1.90 to -0.22, all P>0.05). The logistic regression analysis confirmed sTg as an independent risk factor of SIR in both TCV-PTC group (odds ratio ( OR) = 25.156, 95% CI: 2.245-281.812, P=0.009) and PTC-TCF group ( OR=19.214, 95% CI: 2.537-145.502, P=0.004). The ROC curve indicated that the cut-off value of sTg for predicting SIR was 20.75μg/L in TCV-PTC group and 18.55μg/L in PTC-TCF group. Conclusions:sTg is the independent risk factor for predicting the poor prognosis of patients with TCV-PTC (sTg≥20.75μg/L) and PTC-TCF (sTg≥18.55μg/L). However, other clinical characteristics show no statistical difference between TCV-PTC group and PTC-TCF group, suggesting that the invasiveness of PTC-TCF may not be lower than that of TCV-PTC, which close attention should be paid to in clinical practice.

Due to the specificity of radiopharmaceuticals for targeted α radionuclide therapy, such as radioactivity and radiation damage risk, it is necessary to estimate the internal radiation dose in preclinical evaluation to correctly evaluate the efficacy and safety of the drug, as well as in subsequent clinical studies. This review illustrates current research status of estimating internal radiation dose of targeted α radionuclide therapeutic radiopharmaceuticals based on preclinical studies, in order to add insights for understanding estimation of radiopharmaceuticals internal radiation dose and provide reference for the preclinical evaluation of radiopharmaceuticals.

Objective:To explore the clinicopathologic features differences between tall cell variant of papillary thyroid cancer (TCV-PTC) and PTC with tall cell features (PTC-TCF) and the factors influencing efficacy of 131I therapy in patients with TCV-PTC and PTC-TCF. Methods:A retrospective analysis was conducted on 84 patients (28 males, 56 females, age 43.5(35.0, 55.0) years) with pathologically confirmed TCV-PTC or PTC-TCF and who were treated with 131I therapy from January 2018 to June 2023 in the Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University. The patients were divided into structural incomplete response (SIR) group and non-SIR group according to 131I treatment response. Data differences were analyzed by Wilcoxon rank sum test, Fisher exact test, or Mann-Whitney U test. Variables with P<0.1 were enrolled in logistic multivariate regression analysis. The ROC curve was used to obtain the cut-off value of stimulated thyroglobulin (sTg). Results:A total of 37 patients with non-SIR and 6 patients with SIR were found in TCV-PTC group ( n=43), and 33 non-SIR and 8 SIR cases were found in PTC-TCF group ( n=41). Univariate analysis revealed that sTg differed significantly between non-SIR patients and SIR patients in TCV-PTC group ( Z=-2.81, P=0.003), while no significant differences observed for sex, age, multifocality, capsular invasion, T stage, N stage, B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF) V600E mutation, initial recurrence risk, number of metastatic lymph nodes, maximum tumor diameter ( Z values: from -0.74 to -0.11, all P>0.05). In TCV-PTC group, sTg also differed significantly between non-SIR patients and SIR patients ( Z=-4.40, P<0.001), while the other clinical factors above and the proportion of tall cells showed no significant difference ( Z values: from -1.90 to -0.22, all P>0.05). The logistic regression analysis confirmed sTg as an independent risk factor of SIR in both TCV-PTC group (odds ratio ( OR) = 25.156, 95% CI: 2.245-281.812, P=0.009) and PTC-TCF group ( OR=19.214, 95% CI: 2.537-145.502, P=0.004). The ROC curve indicated that the cut-off value of sTg for predicting SIR was 20.75μg/L in TCV-PTC group and 18.55μg/L in PTC-TCF group. Conclusions:sTg is the independent risk factor for predicting the poor prognosis of patients with TCV-PTC (sTg≥20.75μg/L) and PTC-TCF (sTg≥18.55μg/L). However, other clinical characteristics show no statistical difference between TCV-PTC group and PTC-TCF group, suggesting that the invasiveness of PTC-TCF may not be lower than that of TCV-PTC, which close attention should be paid to in clinical practice.

Objective:To investigate the value of cellular immune status before initial 131I treatment for predicting treatment response in young and middle-aged patients with papillary thyroid cancer (PTC). Methods:From March 2018 to April 2019, 150 young and middle-aged patients with PTC (46 males, 104 females, age (40.0±9.8) years) who underwent total thyroidectomy and neck lymph node dissection in the Affiliated Hospital of Qingdao University were enrolled retrospectively. All patients underwent radioablation 1-2 months after operation, and the serum lymphocyte subsets (CD3 + , CD4 + , CD8 + , CD4/CD8) as well as natural killer (NK) cells were detected 1 d before the initial 131I treatment. Patients were divided into excellent response (ER) group and non-ER group according to the response of 6-12 months after 131I treatment. Clinicopathological characteristics, preablative stimulated thyroglobulin (psTg), initial 131I dose and lymphocyte subsets that might affect the response to 131I treatment were analyzed (independent-sample t test, Mann-Whitney U test, χ2 test, multiple logistic regression analysis). ROC curve analysis was used to evaluate the predictive value of significant factors for non-ER. Results:Of 150 patients, 84 cases were in ER group (56.00%), and 66 cases (44.00%) were in non-ER group. Age ( z=-2.86, P=0.004), M stage ( χ2=13.64, P<0.001), psTg ( z=-8.94, P<0.001), initial 131I dose ( z=-7.60, P<0.001), CD4 + ( t=2.50, P=0.014), CD4/CD8 ( z=-2.22, P=0.027) of the two groups were significantly different. Multivariate analysis showed that psTg (odds ratio ( OR)=1.27, 95% CI: 1.16-1.40, P<0.001) and CD4/CD8 ( OR=0.39, 95% CI: 0.15-0.99, P=0.048) were independent factors for predicting 131I treatment response. The cut-off values of psTg and CD4/CD8 for predicting non-ER were 6.78 μg/L and 1.67, respectively. Conclusions:Cellular immune status before initial 131I treatment may predict treatment response in young and middle-aged patients with PTC. It indicates non-ER response when Tg is higher than 6.78 μg/L and CD4/CD8 is lower than 1.67.

Objective:To investigate the preoperative diagnostic value of 99Tc m-methoxyisobutylisonitrile (MIBI) planar imaging and SPECT/CT imaging for primary hyperparathyroidism (PHPT), and analyze the relevant factors affecting the imaging results. Methods:From June 2016 to September 2019, a total of 62 patients (15 males, 47 females, age range: 27-80 years) confirmed as PHPT by postsurgical pathology in Affiliated Hospital of Qingdao University were retrospectively enrolled. The diagnostic efficacies of 99Tc m-MIBI planar imaging and SPECT/CT imaging were compared using χ2 test. The differences of preoperative serum parathyroid hormone (PTH), Ca and the maximum diameter of lesion between the positive and negative groups of planar imaging were analyzed using independent-sample t test and Mann-Whitney U test. The region of interest (ROI) method was applied to calculate the uptake ratio of lesions to normal tissues at the early phase (T/Ne) and delayed phase (T/Nd) in positive cases of planar imaging. Pearson or Spearman correlation analysis was used to evaluate the correlation of T/Ne, T/Nd with preoperative serum PTH, Ca and the maximum diameter of lesion. The receiver operating characteristic (ROC) curves of preoperative serum PTH, Ca and positive planar imaging were drawn and the cut-off values were obtained. Results:The sensitivity of planar imaging and SPECT/CT imaging was 69.35%(43/62) and 87.10%(54/62) respectively ( χ2=5.729, P=0.017). The preoperative serum PTH, Ca levels and the maximum diameter of lesion in patients with positive planar imaging (253.32(107.00, 331.70) ng/L, 2.78(2.51, 2.87) mmol/L, (2.01±0.88) mm) were higher than those with negative planar imaging ((111.86±44.29) ng/L, (2.59±0.21) mmol/L, (1.42±0.55) mm; z values: -2.802, -1.978, t=3.300, all P<0.05). T/Ne was positively correlated with preoperative serum PTH ( rs=0.511, P<0.001) and the maximum diameter of lesion ( r=0.381, P=0.012), and T/Nd was positively correlated with preoperative serum PTH ( rs=0.538, P<0.001), Ca ( rs=0.348, P=0.022) and the maximum diameter of lesion ( r=0.463, P=0.002). The area under the ROC curve between preoperative serum PTH, Ca and planar imaging was 0.725 and 0.646, respectively. Preoperative serum PTH had a better predictive value with the optimal cut-off value of 150.4 ng/L. Conclusions:Preoperative serum PTH, Ca and the maximum diameter of lesion are positively correlated with 99Tc m-MIBI uptake in PHPT patients with positive planar imaging results. When preoperative serum PTH is lower than 150.4 ng/L, planar imaging is prone to false negative. SPECT/CT imaging has a significant value in preoperative diagnosis and the combination of PTH and CT can improve the positive rate.

Objective:To investigate the association of muscle mass loss with atherosclerosis in elderly patients with type 2 diabetes mellitus(T2DM).Methods:A total of 322 patients with T2DM aged≥60 years old were divided into muscle mass loss group( n=152) and non-muscle mass loss group( n=170) according to their appendicular skeletal muscle mass index(ASMI). All participants underwent physical examination, dual-energy X-ray absorptiometry check, carotid and lower extremity ultrasound, as well as laboratory tests. Results:Among 322 patients, 49(15.22%) patients were suffered from sarcopenia and 152(47.2%) patients with reduced muscle mass. The carotid and lower extremity atherosclerosis grades in the muscle mass loss group were significantly higher than those in the non-muscle mass loss group( P<0.05), with lower body mass index(BMI), T-score, ASMI, uric acid, and homeostasis model assessment of insulin resistance index( P<0.05). Multivariate logistic regression analysis showed that carotid atherosclerosis and lower extremity atherosclerosis were risk factors for muscle mass loss while BMI and 25-(OH)D 3 were protective factors for muscle mass loss. There existed a consistency in carotid atherosclerosis grade and lower extremity atherosclerosis grade of elderly patients with T2DM( P<0.01). Conclusion:Atherosclerosis has a predictive value for early sarcopenia in elderly patients with T2DM.

Objective To construct a prokaryotic expression system of norovirus (NoⅤ) G Ⅱ-4 strain P protein (P particle and P dimer) and to explore its binding activity and patterns with HBGAs receptor.Methods P domain sequence of GZ121 NoⅤ ORF2 gene was cloned and its phylogenic tree was constructed to identify the gene cluster.The pGEX-4T-1-based expression plasmids were constructed respectively by inserting P domain gene fragments with hinge and P-CDCRGDCFC without hinge,and then transformed into BL21 to express fusion proteins,which was induced with 0.6 mmol/L IPTG at 22℃ overnight.P proteins were purified by thrombin cutting and characterized by FPLC.The binding patterns of NoⅤ P protein to HBGAs antigens were analyzed by EIA.Results P region gene of GZ121 belonged to genotype G Ⅱ.4/2004 cluster.SDS-PAGE analysis showed the relative molecular weight of P particle and P dimer was about 36×103,which was consistent with other reports.The peak appeared at 830×103 confirmed the formation of P particle by FPLC.The expression of P protein was further confirmed by Western blot.The EIA results showed that GZ121 P protein could bind to saliva of A-group,B-group and O-group secretors,but not to nonsecretor.The binding affinity of P particle was 80-100 times higher than that of P dimer.Compared with VA387 P particle,it showed stronger binding affinity to O-group,but weaker to A-group.Conclusion The NoⅤ GⅡ-4 GZ121 P proteins including P particle and P dimer were successfully expressed and HBGAs receptor binding assays were established.This pave the way for further studies on the evolution dynamics of NoⅤ G Ⅱ.4 strains and the development of NoⅤ vaccines.

OBJECTIVETo investigate the effect of Baoganning (BGN) on activity of nuclear transcription factor-kappaB (NF-kappaB) in hepatic stellate cells (HSCs) and its relevant mechanisms.

METHODSNormal Wistar rats were medicated with BGN decoction by gavage for 7 days to prepare BGN drug-serum. The effect of BGN drug-serum on HSC-T6 growth was measured by MTT assay; phosphorylation level of NF-kappaB inhibiting factor IkappaB at different time after BGN stimulation was detected by Western blotting analysis; and the binding level of NF-kappaB with DNA was measured 30 min after drug-serum stimulation with gel shift assay.

RESULTSBGN could significantly inhibit the HSC-T6 growth and quickly supress the phosphorylation of IkappaB, with the effect reached its peak at 30 min and restored to baseline level 6 h after stimulation, and reduce the binding capacity of NF-kappaB with DNA.

CONCLUSIONBGN can inhibit phosphorylation of IkappaB, restrain the activity of NF-kappaB and change the binding level of NF-kappaB with DNA.

Animals ; Cells, Cultured ; DNA ; drug effects ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hepatocytes ; cytology ; metabolism ; Male ; NF-kappa B ; drug effects ; genetics ; metabolism ; Phosphorylation ; drug effects ; Random Allocation ; Rats ; Rats, Wistar

Animals ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Hepatocytes ; drug effects ; metabolism ; Humans ; Kruppel-Like Factor 6 ; Kruppel-Like Transcription Factors ; NF-kappa B ; metabolism ; Proto-Oncogene Proteins ; RNA, Messenger ; metabolism ; Trans-Activators ; genetics ; metabolism ; Transcription Factor AP-1 ; metabolism ; Transcription Factors ; pharmacology