1.Preparation and evaluation of in-house Factor Ⅷ inhibitor-positive quality-control samples
Tiantian WANG ; Jie WANG ; Jia DU ; Xunbei HUANG ; Hehe WANG ; Cuicui QIAO ; Wei LIU ; Jing ZHOU ; Jun YANG ; Yunhai FAN
Chinese Journal of Clinical Laboratory Science 2025;43(11):842-844
Objective To prepare in-house coagulation factor Ⅷ(F Ⅷ)inhibitor-positive control material and evaluate its perform-ance.Methods Frozen plasma samples from hemophilia A patients with positive factor Ⅷ inhibitors were pooled,and diluted with Owren's Veronal Buffer(OVB)to 1 BU/mL of the inhibitor concentration in the mixture,then aliquoted and freeze-stored.The homo-geneity and stability of the in-house quality control material were verified,and its suitability was further assessed through intra-laborato-ry reproducibility among different technologists and inter-laboratory comparisons.Results Twenty-one aliquots were randomly tested for homogeneity assessment,yielding an average of 1.05 BU/mL(range 0.9-1.15 BU/mL),with a standard deviation(SD)of 0.083 and coefficient of variation(CV)of 7.90%.The freshly prepared inhibitor-positive control samples contained a concentration of 1.03 BU/mL.After storage at-80℃ for 24 hours,1 week,1 month,2 months,3 months,4 months,5 months,6 months,7 months,8 months,and 9 months,thawed the samples showed relative deviations of 9%,0%,10%,9%,14%,15%,6%,0%,-10%,-5%,and 2%,respectively.The intra-laboratory CV value from different technologists at this center was 7.28%,and the inter-labora-tory CV across different centers was 18.75%.Conclusion The prepared in-house positive control material of Factor Ⅷ inhibitor ex-hibited adequate uniformity and stability.
2.Effect of tyrosine kinase receptor binding protein B3 on the synapse-associated protein and synaptic structure in the hippocampus of epileptic rats model
Tiantian LIU ; Hengfang LIU ; Yanjie JIA
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(9):774-782
Objective:To investigate the effect of tyrosine kinase receptor binding protein B3 (Ephrin-B3) on the expressions of postsynaptic density protein 95 (PSD95), N-methyl-D-aspartic acid (NMDA) receptor subunit 2A and 2B(NR2A/NR2B) and synaptic ultrastructure of hippocampal neurons in the dentate gyrus (DG)area of epileptic rats.Methods:A total of 96 SPF-grade adult male Sprague Dawley(SD) rats were divided into blank group, epilepsy group, lentiviral vectors control group and Ephrin-B3 overexpression group( n=24 in each group) according to the random number table.Another 36 adult male SD rats were randomly divided into recombinant adeno-associated virus control group and Ephrin-B3 suppression group( n=18 in each group). The viruses were stereotaxically injected into bilateral hippocampus DG area of rats and epileptic model was established by intraperitoneal injection of lithium chloride and pilocarpine.Racine standard grading method was used to evaluate seizure rate and the duration and latency of epileptic rats were observed. Immunofluorescence staining was used to observe expression levels of PSD95, NR2A and NR2B protein in hippocampus DG area of rats.PCR and Western blot were used to detect the expression levels of PSD95, NR2A and NR2B mRNA and protein in hippocampus of rats. Transmission electron microscopy was used to observe the ultrastructure of hippocampal neurons in rats. GraphPad Prsim 8 software was used for statistical analysis. Results:(1) The results of Ephrin-B3 overexpression experiment: there were statistically significant differences in the seizure latency and duration among the four groups( F=368.30, 120.00, both P<0.01). The seizure latency in Ephrin-B3 overexpression group was longer than that of the epilepsy group and lentiviral vectors control group((31.32±1.10)d, (24.09±2.02)d, (21.42±0.79)d)(all P<0.01), while the seizure duration in Ephrin-B3 overexpression group was shorter than that of the epilepsy group and lentiviral vectors control group((26.85±1.14)s, (40.40±1.26)s, (36.50±5.50)s)(all P<0.05). Immunofluorescence staining showed the average fluorescence intensity of PSD95, NR2A and NR2B in Ephrin-B3 overexpression group were higher than that in the lentiviral vectors control group(all P<0.01). PCR and Western blot both showed that the Ephrin-B3 overexpression group had higher mRNA expression levels of PSD95, NR2A and NR2B than that in lentiviral vectors control group(all P<0.05). The results of transmission electron microscopy showed the number of synapses in the Ephrin-B3 overexpression group was greater than that in lentiviral vectors control group((9.00±1.00), (6.00±1.00))( P<0.05), synaptic gap was narrower than that in lentiviral vectors control group ((31.60±1.45)nm, (36.43±2.22)nm)(all P<0.05). (2)The results of the Ephrin-B3 suppression experiment: the evaluation of seizures in rats showed that there were statistically significant differences in the seizure latency and duration between recombinant adeno-associated virus control group and Ephrin-B3 suppression groups( t=3.88, 3.93, both P<0.05). The seizure latency in Ephrin-B3 suppression group was shorter than that of recombinant adeno-associated virus control group ((17.10±1.88)d, (23.50±2.15)d)( P<0.05). The seizure duration in Ephrin-B3 suppression group was longer than that of recombinant adeno-associated virus control group((55.16±5.48)s, (42.06±1.83)s)( P<0.05). Western blot results showed that the Ephrin-B3 suppression group had lower protein expression levels of PSD95, NR2A and NR2B than those in recombinant adeno-associated virus control group(all P<0.01). The results of transmission electron microscopy showed the numbers of synapses in the Ephrin-B3 suppression group were less than recombinant adeno-associated virus control group((3.33±0.58), (4.66±0.58))( P<0.05), synaptic gap were narrower than recombinant adeno-associated virus control group((37.27±0.97)nm, (33.33±1.46)nm)( P<0.05). Conclusion:Ephrin-B3 can attenuate seizures and upregulate the synaptic related proteins and glutamate receptor expression, improving synaptic structure.
3.Preparation and evaluation of in-house Factor Ⅷ inhibitor-positive quality-control samples
Tiantian WANG ; Jie WANG ; Jia DU ; Xunbei HUANG ; Hehe WANG ; Cuicui QIAO ; Wei LIU ; Jing ZHOU ; Jun YANG ; Yunhai FAN
Chinese Journal of Clinical Laboratory Science 2025;43(11):842-844
Objective To prepare in-house coagulation factor Ⅷ(F Ⅷ)inhibitor-positive control material and evaluate its perform-ance.Methods Frozen plasma samples from hemophilia A patients with positive factor Ⅷ inhibitors were pooled,and diluted with Owren's Veronal Buffer(OVB)to 1 BU/mL of the inhibitor concentration in the mixture,then aliquoted and freeze-stored.The homo-geneity and stability of the in-house quality control material were verified,and its suitability was further assessed through intra-laborato-ry reproducibility among different technologists and inter-laboratory comparisons.Results Twenty-one aliquots were randomly tested for homogeneity assessment,yielding an average of 1.05 BU/mL(range 0.9-1.15 BU/mL),with a standard deviation(SD)of 0.083 and coefficient of variation(CV)of 7.90%.The freshly prepared inhibitor-positive control samples contained a concentration of 1.03 BU/mL.After storage at-80℃ for 24 hours,1 week,1 month,2 months,3 months,4 months,5 months,6 months,7 months,8 months,and 9 months,thawed the samples showed relative deviations of 9%,0%,10%,9%,14%,15%,6%,0%,-10%,-5%,and 2%,respectively.The intra-laboratory CV value from different technologists at this center was 7.28%,and the inter-labora-tory CV across different centers was 18.75%.Conclusion The prepared in-house positive control material of Factor Ⅷ inhibitor ex-hibited adequate uniformity and stability.
4.Diagnostic value of gradient characteristics of quantitative parameters of contrast-enhanced ultrasound for papillary thyroid carcinoma
Ying XUE ; Tiantian JIA ; Le REN ; Gaiqin XUE
Cancer Research and Clinic 2025;37(9):672-678
Objective:To explore the diagnostic value of gradient characteristics of quantitative parameters of contrast-enhanced ultrasound (CEUS) in papillary thyroid carcinoma.Methods:A retrospective case series study was conducted. The clinical data of 120 patients with thyroid diseases who underwent pathological examination for samples collected through fine needle aspiration or surgical resection and underwent CEUS examination before surgery at Shanxi Province Cancer Hospital from January 2018 to May 2023 were collected. A total of 120 thyroid nodules were selected and divided into the benign group (37 nodules) and the malignant group (83 nodules) according to pathological results. The VueBox software was used to depict the four regions of interest in nodules of the two groups, which were the overall, central and marginal areas and surrounding normal thyroid tissues. The time-intensity curve (TIC) was drawn and the relevant parameters including peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-out rate (WoR), and time to increase (TI) were analyzed, and the gradient values (ΔPE within the nodules, ΔWiAUC within the nodules, ΔWiR within the nodules, ΔWoR within the nodules, ΔTI within the nodules) between two groups of nodules and surrounding normal tissues, as well as between the central and marginal areas of the nodules were calculated.Results:The conventional ultrasound characteristics of benign and malignant nodules showed only a statistically significant difference in aspect ratio ( χ2 = 14.76, P < 0.001). There were statistically significant differences in PE, WiAUC, WiR, and WoR between the overall malignant nodules and the surrounding normal tissues, as well as between the central and marginal areas within the nodules (all P < 0.05); there was a statistically significant difference in WiAUC between the overall benign nodules and the surrounding normal tissues (7 362.06 vs. 7 281.16, Z = -2.07, P = 0.038); there was no statistically significant difference in TI between the two groups of overall nodules and the surrounding normal tissues, as well as the central and marginal areas within the nodules (both P > 0.05); there were statistically significant differences in ΔPE, ΔWiAUC, ΔWiR, and ΔWoR in different regions of the nodules between the two groups (all P < 0.05); binary logistic analysis showed that overall ΔPE and intra nodule ΔWoR were independent predictive factors for the malignancy of thyroid nodules (both P < 0.05); receiver operating characteristic (ROC) curve analysis showed that the overall ΔPE had better diagnostic efficacy for benign and malignant thyroid nodules than the intra nodule ΔWoR, with a cut-off value of -536.23 a.u. Its combination with CEUS had the highest diagnostic efficacy for malignant thyroid nodules, with sensitivity, specificity, positive predictive value, and negative predictive value of 86.7%, 81.1%, 91.1%, and 73.2%, respectively. Conclusions:The peak intensity gradient value (overall ΔPE) between thyroid nodules and surrounding normal tissues can serve as an effective indicator for distinguishing between benign and malignant thyroid nodules. The combination of overall ΔPE and CEUS has good diagnostic efficacy.
5.Effect of tyrosine kinase receptor binding protein B3 on the synapse-associated protein and synaptic structure in the hippocampus of epileptic rats model
Tiantian LIU ; Hengfang LIU ; Yanjie JIA
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(9):774-782
Objective:To investigate the effect of tyrosine kinase receptor binding protein B3 (Ephrin-B3) on the expressions of postsynaptic density protein 95 (PSD95), N-methyl-D-aspartic acid (NMDA) receptor subunit 2A and 2B(NR2A/NR2B) and synaptic ultrastructure of hippocampal neurons in the dentate gyrus (DG)area of epileptic rats.Methods:A total of 96 SPF-grade adult male Sprague Dawley(SD) rats were divided into blank group, epilepsy group, lentiviral vectors control group and Ephrin-B3 overexpression group( n=24 in each group) according to the random number table.Another 36 adult male SD rats were randomly divided into recombinant adeno-associated virus control group and Ephrin-B3 suppression group( n=18 in each group). The viruses were stereotaxically injected into bilateral hippocampus DG area of rats and epileptic model was established by intraperitoneal injection of lithium chloride and pilocarpine.Racine standard grading method was used to evaluate seizure rate and the duration and latency of epileptic rats were observed. Immunofluorescence staining was used to observe expression levels of PSD95, NR2A and NR2B protein in hippocampus DG area of rats.PCR and Western blot were used to detect the expression levels of PSD95, NR2A and NR2B mRNA and protein in hippocampus of rats. Transmission electron microscopy was used to observe the ultrastructure of hippocampal neurons in rats. GraphPad Prsim 8 software was used for statistical analysis. Results:(1) The results of Ephrin-B3 overexpression experiment: there were statistically significant differences in the seizure latency and duration among the four groups( F=368.30, 120.00, both P<0.01). The seizure latency in Ephrin-B3 overexpression group was longer than that of the epilepsy group and lentiviral vectors control group((31.32±1.10)d, (24.09±2.02)d, (21.42±0.79)d)(all P<0.01), while the seizure duration in Ephrin-B3 overexpression group was shorter than that of the epilepsy group and lentiviral vectors control group((26.85±1.14)s, (40.40±1.26)s, (36.50±5.50)s)(all P<0.05). Immunofluorescence staining showed the average fluorescence intensity of PSD95, NR2A and NR2B in Ephrin-B3 overexpression group were higher than that in the lentiviral vectors control group(all P<0.01). PCR and Western blot both showed that the Ephrin-B3 overexpression group had higher mRNA expression levels of PSD95, NR2A and NR2B than that in lentiviral vectors control group(all P<0.05). The results of transmission electron microscopy showed the number of synapses in the Ephrin-B3 overexpression group was greater than that in lentiviral vectors control group((9.00±1.00), (6.00±1.00))( P<0.05), synaptic gap was narrower than that in lentiviral vectors control group ((31.60±1.45)nm, (36.43±2.22)nm)(all P<0.05). (2)The results of the Ephrin-B3 suppression experiment: the evaluation of seizures in rats showed that there were statistically significant differences in the seizure latency and duration between recombinant adeno-associated virus control group and Ephrin-B3 suppression groups( t=3.88, 3.93, both P<0.05). The seizure latency in Ephrin-B3 suppression group was shorter than that of recombinant adeno-associated virus control group ((17.10±1.88)d, (23.50±2.15)d)( P<0.05). The seizure duration in Ephrin-B3 suppression group was longer than that of recombinant adeno-associated virus control group((55.16±5.48)s, (42.06±1.83)s)( P<0.05). Western blot results showed that the Ephrin-B3 suppression group had lower protein expression levels of PSD95, NR2A and NR2B than those in recombinant adeno-associated virus control group(all P<0.01). The results of transmission electron microscopy showed the numbers of synapses in the Ephrin-B3 suppression group were less than recombinant adeno-associated virus control group((3.33±0.58), (4.66±0.58))( P<0.05), synaptic gap were narrower than recombinant adeno-associated virus control group((37.27±0.97)nm, (33.33±1.46)nm)( P<0.05). Conclusion:Ephrin-B3 can attenuate seizures and upregulate the synaptic related proteins and glutamate receptor expression, improving synaptic structure.
6.Investigation of attention deficit hyperactivity disorder and subthreshold states among children in Chongqing
Xiuying YANG ; Zhanming SHI ; Yi LI ; Jiasheng LIU ; Dengguo CHENG ; Tingting HE ; Wei ZHAO ; Gang YUAN ; Ludan ZHANG ; Chunni HUANG ; Junhao LUAN ; Xiaoyue JIA ; Tiantian CHEN ; Mei WANG ; Shiping ZHENG ; Chunying WU ; Yuanming REN ; Mengfei LI
Sichuan Mental Health 2025;38(6):561-567
BackgroundAttention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by age-inappropriate inattention, excessive activities incongruous with setting, and emotional impulsivity. Subthreshold ADHD (sADHD) is clinically defined as the presence of ADHD symptoms that do not meet the full diagnostic criteria for ADHD. Children with sADHD exhibit deficits in executive function, demonstrate more conduct, learning, and anxiety-related problems compared to typically developing children, and show even poorer working memory performance than children diagnosed with ADHD. Currently, there is limited epidemiological research on sADHD in China, with few studies simultaneously investigating the prevalence of both ADHD and sADHD in children. ObjectiveTo investigate the prevalence of ADHD and sADHD among children aged 6–13 years in Chongqing, analyzing their distribution characteristics within this population, with the aim of providing references for developing preventive measures against both ADHD and sADHD. MethodsFrom October to November 2023, a total of 3 398 students in grades 1–6 from six primary schools in Jiangbei District, Chongqing were selected using a stratified cluster random sampling method. The occurrence of ADHD and sADHD was evaluated by using the short version (18-item version) of the Swanson, Nolan, and Pelham IV rating scales (SNAP-IV) and the Chinese vision of Schedule for Affective Disorder and Schizophrenia for School-aged Children-Present and Lifetime Version (K-SADS-PL). ResultsThe ADHD detection rate among children in Chongqing was 1.90% (95% CI: 0.014–0.024). Boys showed a significantly higher ADHD detection rate than girls (χ2=7.733, P=0.005). No statistically significant differences were found in ADHD detection rates across different grades or age groups (χ2=7.347, 12.362, P>0.05). The sADHD detection rate was 6.32% (95% CI: 0.054–0.072). Similarly, boys exhibited significantly higher sADHD detection rates than girls (χ2=21.005, P<0.01). Significant differences emerged across different grades (χ2=20.559, P=0.001), while no statistically significant difference was observed in age groups (χ2=12.070, P=0.060). ConclusionThe ADHD detection rates were comparable across all grade levels and age groups from 6–13 years old. Second-grade children demonstrated notably higher sADHD rates compared to other grades, while boys demonstrated higher prevalence rates than girls for both ADHD and sADHD. [Funded by Science and Health Joint Medical Research Project in Jiangbei District, Chongqing City in the Second Half of 2023 (number, 2023JBKWLH022)]
7.Diagnostic value of contrast-enhanced ultrasound quantitative analysis for C-TIRADS 4 thyroid nodules
Tiantian JIA ; Gaiqin XUE ; Ying XUE ; Le REN
Cancer Research and Clinic 2025;37(4):273-279
Objective:To explore the diagnostic value of quantitative analysis of contrast-enhanced ultrasound for the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) thyroid nodules 4.Methods:A retrospective case series study was conducted. A total of 87 patients with thyroid nodules from Shanxi Province Cancer Hospital between October 2018 and July 2022 were selected. All patients were diagnosed as C-TIRADS 4 thyroid nodules by routine ultrasound and had DICOM storage format ultrasound contrast dynamic data. All 96 thyroid nodules in 87 patients had clear surgical and pathological results. Based on the contrast-enhanced ultrasound features of the nodules, the nodules were reclassified by using C-TIRADS according to 3 different criteria. VueBox analysis software was used to obtain dynamic contrast-enhanced ultrasound (DCE-US) quantitative parameters, the most effective quantitative parameters for diagnosing thyroid malignant nodules were obtained by using receiver operating characteristic (ROC) curves, and their optimal cut-off values were obtained. Based on ultrasound contrast and DCE-US quantitative parameters, the nodules were reclassified by using C-TIRADS. Based on pathological results, the malignancy rates of nodules classified by C-TIRADS based on the conventional ultrasound, contrast-enhanced ultrasound, and contrast-enhanced ultrasound combined with DCE-US quantitative parameters were calculated. ROC curves were drawn to compare the diagnostic efficacy of conventional ultrasound, contrast-enhanced ultrasound, and contrast-enhanced ultrasound combined with DCE-US quantitative parameters for thyroid malignant nodules.Results:Among the 96 thyroid nodules, the malignancy rates of C-TIRADS 4a, 4b, and 4c nodules evaluated by conventional ultrasound were 50.0% (17/34), 72.1% (31/43) and 100.0% (19/19), respectively, which were not within the reference range provided by the C-TIRADS guideline. After reclassifying the nodules according to the contrast-enhanced ultrasound standards, the malignancy rates of C-TIRADS 3, 4a, 4b, 4c, 5 of nodules were 0 (0/2), 25.0% (2/8), 31.3% (5/16), 71.9% (23/32), and 97.4% (37/38), respectively. Among them, the malignancy rate of the 4a type nodule was still relatively high, which was not within the reference range given by the C-TIRADS guideline. The area under the curve of DCE-US quantitative parameter peak intensity (PE) for diagnosing thyroid malignant nodules according to ROC curves was the largest with the optimal cut-off value of 2080.7a.u. Based on contrast-enhanced ultrasound and combined with PE, the nodules were classified again, and the malignancy rates of C-TIRADS 3, 4a, 4b, 4c, 5 of nodules were 0 (0/7), 9.1% (1/11), 27.3% (3/11), 83.3% (11/13), and 98.1% (53/54), respectively, all were within the reference range provided by the C-TIRADS guideline. ROC curve analysis showed that the AUC of contrast-enhanced ultrasound combined with DCE-US quantitative parameter PE for diagnosing thyroid malignant nodules was greater than that of conventional ultrasound and contrast-enhanced ultrasound (both P < 0.05); the optimal cut-off value was type 4b, with the sensitivity of 94.0%, the specificity of 89.7%, and the accuracy of 92.7%. Conclusions:The combination of contrast-enhanced ultrasound and DCE-US quantitative parameter PE is helpful for more accurate classification of C-TIRADS 4 thyroid nodules and improves the diagnostic efficiency of thyroid malignant nodules.
8.Diagnostic value of gradient characteristics of quantitative parameters of contrast-enhanced ultrasound for papillary thyroid carcinoma
Ying XUE ; Tiantian JIA ; Le REN ; Gaiqin XUE
Cancer Research and Clinic 2025;37(9):672-678
Objective:To explore the diagnostic value of gradient characteristics of quantitative parameters of contrast-enhanced ultrasound (CEUS) in papillary thyroid carcinoma.Methods:A retrospective case series study was conducted. The clinical data of 120 patients with thyroid diseases who underwent pathological examination for samples collected through fine needle aspiration or surgical resection and underwent CEUS examination before surgery at Shanxi Province Cancer Hospital from January 2018 to May 2023 were collected. A total of 120 thyroid nodules were selected and divided into the benign group (37 nodules) and the malignant group (83 nodules) according to pathological results. The VueBox software was used to depict the four regions of interest in nodules of the two groups, which were the overall, central and marginal areas and surrounding normal thyroid tissues. The time-intensity curve (TIC) was drawn and the relevant parameters including peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-out rate (WoR), and time to increase (TI) were analyzed, and the gradient values (ΔPE within the nodules, ΔWiAUC within the nodules, ΔWiR within the nodules, ΔWoR within the nodules, ΔTI within the nodules) between two groups of nodules and surrounding normal tissues, as well as between the central and marginal areas of the nodules were calculated.Results:The conventional ultrasound characteristics of benign and malignant nodules showed only a statistically significant difference in aspect ratio ( χ2 = 14.76, P < 0.001). There were statistically significant differences in PE, WiAUC, WiR, and WoR between the overall malignant nodules and the surrounding normal tissues, as well as between the central and marginal areas within the nodules (all P < 0.05); there was a statistically significant difference in WiAUC between the overall benign nodules and the surrounding normal tissues (7 362.06 vs. 7 281.16, Z = -2.07, P = 0.038); there was no statistically significant difference in TI between the two groups of overall nodules and the surrounding normal tissues, as well as the central and marginal areas within the nodules (both P > 0.05); there were statistically significant differences in ΔPE, ΔWiAUC, ΔWiR, and ΔWoR in different regions of the nodules between the two groups (all P < 0.05); binary logistic analysis showed that overall ΔPE and intra nodule ΔWoR were independent predictive factors for the malignancy of thyroid nodules (both P < 0.05); receiver operating characteristic (ROC) curve analysis showed that the overall ΔPE had better diagnostic efficacy for benign and malignant thyroid nodules than the intra nodule ΔWoR, with a cut-off value of -536.23 a.u. Its combination with CEUS had the highest diagnostic efficacy for malignant thyroid nodules, with sensitivity, specificity, positive predictive value, and negative predictive value of 86.7%, 81.1%, 91.1%, and 73.2%, respectively. Conclusions:The peak intensity gradient value (overall ΔPE) between thyroid nodules and surrounding normal tissues can serve as an effective indicator for distinguishing between benign and malignant thyroid nodules. The combination of overall ΔPE and CEUS has good diagnostic efficacy.
9.Diagnostic value of contrast-enhanced ultrasound quantitative analysis for C-TIRADS 4 thyroid nodules
Tiantian JIA ; Gaiqin XUE ; Ying XUE ; Le REN
Cancer Research and Clinic 2025;37(4):273-279
Objective:To explore the diagnostic value of quantitative analysis of contrast-enhanced ultrasound for the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) thyroid nodules 4.Methods:A retrospective case series study was conducted. A total of 87 patients with thyroid nodules from Shanxi Province Cancer Hospital between October 2018 and July 2022 were selected. All patients were diagnosed as C-TIRADS 4 thyroid nodules by routine ultrasound and had DICOM storage format ultrasound contrast dynamic data. All 96 thyroid nodules in 87 patients had clear surgical and pathological results. Based on the contrast-enhanced ultrasound features of the nodules, the nodules were reclassified by using C-TIRADS according to 3 different criteria. VueBox analysis software was used to obtain dynamic contrast-enhanced ultrasound (DCE-US) quantitative parameters, the most effective quantitative parameters for diagnosing thyroid malignant nodules were obtained by using receiver operating characteristic (ROC) curves, and their optimal cut-off values were obtained. Based on ultrasound contrast and DCE-US quantitative parameters, the nodules were reclassified by using C-TIRADS. Based on pathological results, the malignancy rates of nodules classified by C-TIRADS based on the conventional ultrasound, contrast-enhanced ultrasound, and contrast-enhanced ultrasound combined with DCE-US quantitative parameters were calculated. ROC curves were drawn to compare the diagnostic efficacy of conventional ultrasound, contrast-enhanced ultrasound, and contrast-enhanced ultrasound combined with DCE-US quantitative parameters for thyroid malignant nodules.Results:Among the 96 thyroid nodules, the malignancy rates of C-TIRADS 4a, 4b, and 4c nodules evaluated by conventional ultrasound were 50.0% (17/34), 72.1% (31/43) and 100.0% (19/19), respectively, which were not within the reference range provided by the C-TIRADS guideline. After reclassifying the nodules according to the contrast-enhanced ultrasound standards, the malignancy rates of C-TIRADS 3, 4a, 4b, 4c, 5 of nodules were 0 (0/2), 25.0% (2/8), 31.3% (5/16), 71.9% (23/32), and 97.4% (37/38), respectively. Among them, the malignancy rate of the 4a type nodule was still relatively high, which was not within the reference range given by the C-TIRADS guideline. The area under the curve of DCE-US quantitative parameter peak intensity (PE) for diagnosing thyroid malignant nodules according to ROC curves was the largest with the optimal cut-off value of 2080.7a.u. Based on contrast-enhanced ultrasound and combined with PE, the nodules were classified again, and the malignancy rates of C-TIRADS 3, 4a, 4b, 4c, 5 of nodules were 0 (0/7), 9.1% (1/11), 27.3% (3/11), 83.3% (11/13), and 98.1% (53/54), respectively, all were within the reference range provided by the C-TIRADS guideline. ROC curve analysis showed that the AUC of contrast-enhanced ultrasound combined with DCE-US quantitative parameter PE for diagnosing thyroid malignant nodules was greater than that of conventional ultrasound and contrast-enhanced ultrasound (both P < 0.05); the optimal cut-off value was type 4b, with the sensitivity of 94.0%, the specificity of 89.7%, and the accuracy of 92.7%. Conclusions:The combination of contrast-enhanced ultrasound and DCE-US quantitative parameter PE is helpful for more accurate classification of C-TIRADS 4 thyroid nodules and improves the diagnostic efficiency of thyroid malignant nodules.
10.Serum metabolomic characteristics of early papillary thyroid carcinoma and association with lymph node metastasis
Shaojun BO ; Chenhui JIA ; Tiantian WANG ; Qingyan LI ; Weizhe XU ; Xianfa XU
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(2):85-91
OBJECTIVE To compare the metabolomic characteristics of stage T1 papillary thyroid carcinoma(PTC)and nodular goiter(NG),and the relationship between metabolites and lymph node metastasis of PTC.METHODS Serum samples were collected from 60 patients with stage T1 PTC and 30 patients with NG who underwent thyroidectomy at the Department of Otolaryngology Head and Neck Surgery,Civil Aviation General Hospital between September 2021 and April 2022.The PTC group was divided into the N+ group with lymph node metastasis and the N-group without lymph node metastasis according to the presence or absence of lymph node metastasis.The serum metabolites of the N+ and N-groups and the PTC and NG groups were compared and analyzed using an ultra-performance liquid chromatography-mass spectrometry(UPLC-Q-Exactive-MS)coupled platform,and principal component analysis(PCA),partial least squares discriminant analysis(PLS-DA),and orthogonal partial least squares discriminant analysis(OPLS-DA)was performed using SIMCA-P 14.1 software.OPLS-DA modeling,combined with FDR-corrected Mann-Whitney-Wilcoxon test results and metabolite difference multiples in the two groups undergoing comparison,etc.to screen for potential small molecule metabolic markers,and to establish a joint diagnostic model by binary logistic regression analysis.RESULTS There were no significant differential metabolites between the N+ group with lymph node metastasis and the N-group without lymph node metastasis.Seven differential metabolites were found between PCA patients and NG patients,and the five relevant metabolic pathways were the pentose phosphate pathway,pentose and glucuronide interconversion,glycolysis/gluconeogenesis,fructose,and mannose metabolism,and fatty acid biosynthesis.The differential metabolite with an area under the ROC curve>0.9 was D-glyceraldehyde 3-phosphate,and another N-undecanoylglycine,uronic acid,and the area under the ROC curve for three metabolites,N-undecanoylglycine,uric acid,and triiodothyronine glucuronide,was>0.8.CONCLUSION PTC patients differed from NG patients mainly in glucose metabolism and lipid metabolism,and D-glyceraldehyde 3-phosphate could be distinguished from NG patients with the aid of N-undecanoylglycine,uric acid,and triiodothyronine glucuronide,combined with imaging findings.Also,no significant differences in serum metabolites were found in the N+ group compared with the N-group,and the presence or absence of lymph node metastases did not affect serum metabolites in patients with stage T1 PTC.

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