Objective:To investigate the clinical and pathological significance of the DICER1 mutation in follicular thyroid carcinoma (FTC).Methods:Sixty-eight cases of primary FTC resected between 2009 and 2023 were retrieved from The Affiliated Hospital of Qingdao University, Qingdao, China. Sanger sequencing was performed to identify DICER1 and TERT promoter mutations in all cases. Cases with DICER1 or TERT promoter mutations were subject to additional examination of potential mutations in KRAS, HRAS, and NRAS. The clinical and pathological features of DICER1-mutant FTCs were then analyzed. The relationship between DICER1 mutations and TERT-promoter/RAS mutations was also assessed.Results:DICER1 mutations were detected in 16 of the 68 FTC cases (23.5%), with 11 near E1813 at exon 25, 6 near D1709 at exon 24, and 1 in the splice region of exon 25. Two cases harbored two (distinct) mutations. All patients with DICER1-mutant FTC were female. Compared with patients with DICER1-wild-type FTC, those with DICER1-mutant were much younger, and had a higher proportion of minimally invasive subtype. Nine FTCs with DICER1 mutations were subject to further sequencing on adjacent non-cancerous tissues or lymph node tissues, but no mutations were detected. TERT-promoter or RAS hotspot mutations were not identified in any of the DICER1-mutant cases. However, TERT-promoter mutation was found in 6 DICER1-wild-type cases (8.8%, 6/68), with 3 cases also having RAS hotspot mutations and exhibiting highly aggressive biological behaviors.Conclusion:DICER1 mutations may occur in FTCs and appear mutually exclusive with RAS and TERT-promoter mutations, warranting further study as RAS-like mutations.

Pediatric nuclear medicine achieve precise functional and metabolic assessments with renal dynamic imaging,bone scintigraphy and 18F-FDG PET/CT,playing irreplaceable role for diagnosis and treatment of pediatric diseases.The emergence of novel molecular imaging probes,such as 68 Ga-DOT AT ATE,18F-DOPA and 18F-MFBG,expand clinical application field of pediatric nuclear medicine,while radionuclide therapy using 131I,131I-MIBG and 177 Lu-DOT AT ATE offer targeted options for pediatric thyroid cancer and neuroendocrine tumors.The current status,challenges and future prospect of pediatric nuclear medicine were reviewed in this article.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Background and aims:Environmental pollutants,particularly organochlorine insecticides like endosulfan(ENDO),are increasingly linked to liver toxicity and related diseases.Despite its widespread historical use,the mechanisms underlying ENDO-induced liver damage remain poorly understood.This study aims to elucidate the cellular and molecular mechanisms of ENDO-induced hepatotoxicity.Methods:C57BL/6 mice were exposed to ENDO for two weeks.Single-cell RNA sequencing(scRNA-seq)was subsequently performed on mouse livers to explore ENDO-induced hepatotoxicity at the single-cell level.Differentially expressed genes(DEGs)across cell types and treatments were identified and then subjected to pathway enrichment to uncover key biological processes affected by ENDO.Transcription factor(TF)regulatory network,pseudotime trajectory,and cellular communication analysis were used to explore the molecular and cellular changes after ENDO exposure.Results:ENDO not only caused direct hepatocyte injury but also activated hepatic stellate cells and lymphocytes,triggering inflammatory responses with upregulation of multiple key chemokines and cytotoxic genes.Additionally,ENDO exposure led to the recruitment and activation of myeloid cells,contributing to the inflammatory milieu.An increase in intercellular communication and changes to the hepatic microenvironment,especially the interaction between activated hepatic stellate cells and CD8+T cells were observed,further implicating these processes in ENDO-induced liver damage.Conclusions:This study provides new insights into the cellular and molecular mechanisms underlying liver injury induced by organochlorine insecticides like ENDO.Key genes and pathways involved in ENDO-associated liver toxicity have been identified at a single-cell resolution.These findings suggest that altered cellular communications and inflammatory responses may play pivotal roles in the pathogenesis of ENDO-induced liver injury.

F-FDG PET/CT is an ideal auxiliary tool for early and accurate diagnosis of malignant tumors in children.This guideline aimed to standardize 18F-FDG PET/CT examination process for malignant tumors in children,hence providing references for nuclear medicine professionals.

Purpose To investigate the diagnostic value of quantitative 123I-Metaiodobenzylguanidine(MIBG)xSPECT/CT imaging in bone metastases of neuroblastoma in children.Materials and Methods We retrospectively assessed 123I-MIBG xSPECT/CT images of 61 children with neuroblastoma confirmed by pathology analyzed the influencing factors of bone metastatic lesions and normal bone quantitative parameters from March 2022 to March 2023 in Beijing Friendship Hospital,Capital Medical University,and compared the differences in standard uptake value(SUV).We used receiver operating characteristics curves to determine the optimum maximum standard uptake value(SUVmax),average standard uptake value(SUVavg),minimum standard uptake value(SUVmin)and peak standard uptake value(SUVpeak)cut-off value to diagnose bone metastatic lesions.Results There was no statistically significant difference in normal bone SUV values among different physical parameters(r=-0.204-0.071,all P>0.05).SUVmax,SUVavg,SUVmin and SUVpeak of bone metastatic lesions were significantly higher than those of normal bone(Z=-10.118--9.703,all P<0.000 1),and there was no significant statistical difference in SUV measurements of bone metastatic lesions among different Curie score intervals(H=0.226,0.107,0.149,0.342,all P>0.05).The area under the curve of SUVmax,SUVavg,SUVmin and SUVpeak were 0.929(95%CI 0.884-0.974),0.948(95%CI 0.906-0.989),0.935(95%CI 0.890-0.981),0.942(95%CI 0.899-0.985);sensitivity was 90.9%,90.2%,93.7%,92.3%,and specificity was 86.9%,93.4%,85.2%,88.5%,respectively,with statistically significant differences(P<0.000 1).The optimal diagnostic thresholds for SUVmax,SUVavg,SUVmin and SUVpeak were 0.39 g/ml,0.33 g/ml,0.20 g/ml and 0.33 g/ml,respectively.Conclusion We demonstrate that SUVavg above 0.33 g/ml in neuroblastoma patients have best diagnostic efficacy in the diagnosis of bone metastasis of neuroblastoma.Quantitative indexes of xSPECT/CT increase the specificity of diagnosing bone metastases of neuroblastoma,demonstrating the high diagnostic efficiency of 123I-MIBG xSPECT/CT imaging quantitative analysis and its potential usefulness as a diagnostic aid for visual evaluation.

Purpose To investigate the diagnostic value of quantitative 123I-Metaiodobenzylguanidine(MIBG)xSPECT/CT imaging in bone metastases of neuroblastoma in children.Materials and Methods We retrospectively assessed 123I-MIBG xSPECT/CT images of 61 children with neuroblastoma confirmed by pathology analyzed the influencing factors of bone metastatic lesions and normal bone quantitative parameters from March 2022 to March 2023 in Beijing Friendship Hospital,Capital Medical University,and compared the differences in standard uptake value(SUV).We used receiver operating characteristics curves to determine the optimum maximum standard uptake value(SUVmax),average standard uptake value(SUVavg),minimum standard uptake value(SUVmin)and peak standard uptake value(SUVpeak)cut-off value to diagnose bone metastatic lesions.Results There was no statistically significant difference in normal bone SUV values among different physical parameters(r=-0.204-0.071,all P>0.05).SUVmax,SUVavg,SUVmin and SUVpeak of bone metastatic lesions were significantly higher than those of normal bone(Z=-10.118--9.703,all P<0.000 1),and there was no significant statistical difference in SUV measurements of bone metastatic lesions among different Curie score intervals(H=0.226,0.107,0.149,0.342,all P>0.05).The area under the curve of SUVmax,SUVavg,SUVmin and SUVpeak were 0.929(95%CI 0.884-0.974),0.948(95%CI 0.906-0.989),0.935(95%CI 0.890-0.981),0.942(95%CI 0.899-0.985);sensitivity was 90.9%,90.2%,93.7%,92.3%,and specificity was 86.9%,93.4%,85.2%,88.5%,respectively,with statistically significant differences(P<0.000 1).The optimal diagnostic thresholds for SUVmax,SUVavg,SUVmin and SUVpeak were 0.39 g/ml,0.33 g/ml,0.20 g/ml and 0.33 g/ml,respectively.Conclusion We demonstrate that SUVavg above 0.33 g/ml in neuroblastoma patients have best diagnostic efficacy in the diagnosis of bone metastasis of neuroblastoma.Quantitative indexes of xSPECT/CT increase the specificity of diagnosing bone metastases of neuroblastoma,demonstrating the high diagnostic efficiency of 123I-MIBG xSPECT/CT imaging quantitative analysis and its potential usefulness as a diagnostic aid for visual evaluation.

F-FDG PET/CT is an ideal auxiliary tool for early and accurate diagnosis of malignant tumors in children.This guideline aimed to standardize 18F-FDG PET/CT examination process for malignant tumors in children,hence providing references for nuclear medicine professionals.

Objective:To investigate the clinical and pathological significance of the DICER1 mutation in follicular thyroid carcinoma (FTC).Methods:Sixty-eight cases of primary FTC resected between 2009 and 2023 were retrieved from The Affiliated Hospital of Qingdao University, Qingdao, China. Sanger sequencing was performed to identify DICER1 and TERT promoter mutations in all cases. Cases with DICER1 or TERT promoter mutations were subject to additional examination of potential mutations in KRAS, HRAS, and NRAS. The clinical and pathological features of DICER1-mutant FTCs were then analyzed. The relationship between DICER1 mutations and TERT-promoter/RAS mutations was also assessed.Results:DICER1 mutations were detected in 16 of the 68 FTC cases (23.5%), with 11 near E1813 at exon 25, 6 near D1709 at exon 24, and 1 in the splice region of exon 25. Two cases harbored two (distinct) mutations. All patients with DICER1-mutant FTC were female. Compared with patients with DICER1-wild-type FTC, those with DICER1-mutant were much younger, and had a higher proportion of minimally invasive subtype. Nine FTCs with DICER1 mutations were subject to further sequencing on adjacent non-cancerous tissues or lymph node tissues, but no mutations were detected. TERT-promoter or RAS hotspot mutations were not identified in any of the DICER1-mutant cases. However, TERT-promoter mutation was found in 6 DICER1-wild-type cases (8.8%, 6/68), with 3 cases also having RAS hotspot mutations and exhibiting highly aggressive biological behaviors.Conclusion:DICER1 mutations may occur in FTCs and appear mutually exclusive with RAS and TERT-promoter mutations, warranting further study as RAS-like mutations.

Pediatric nuclear medicine achieve precise functional and metabolic assessments with renal dynamic imaging,bone scintigraphy and 18F-FDG PET/CT,playing irreplaceable role for diagnosis and treatment of pediatric diseases.The emergence of novel molecular imaging probes,such as 68 Ga-DOT AT ATE,18F-DOPA and 18F-MFBG,expand clinical application field of pediatric nuclear medicine,while radionuclide therapy using 131I,131I-MIBG and 177 Lu-DOT AT ATE offer targeted options for pediatric thyroid cancer and neuroendocrine tumors.The current status,challenges and future prospect of pediatric nuclear medicine were reviewed in this article.