18F-fluorodeoxyglucose positron emission tomography-computed tomography in the localization of the lesions in the osteogenic region of breast cancer bone metastases after therapy.

Background: Accurate efficacy evaluation of bone metastases (BMs) from breast cancer (BC) is an intractable issue in clinical practice, for which solutions are urgently needed. This study aimed to investigate the utility of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in the response evaluation of bone metastasis of BC. Methods: In total, 22 patients diagnosed with BC and BM were enrolled. These patients underwent repeated 18F-FDG PET/CT evaluations. The patients and each BM site were divided into two groups based on their response to treatment: progressive disease (PD) and nonprogressive disease (non-PD). We analyzed and compared the changes in PET and CT images, as well as the serum concentration of carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153), alkaline phosphatase (ALP), and calcium (Ca) over the same time frame. The immunohistochemistry (IHC) of primary lesions between groups and between the primary focus and BM with high 18F-FDG uptake were compared and analyzed. Results: Maximum standard uptake value (SUVmax) after therapy [area under the curve (AUC): 0.932] and Δ-value of SUVmax (AUC: 0.811) on 18F-FDG PET imaging proved significantly valuable for the efficacy of therapy outcomes related to BM lesions (P<0.05). In terms of overall evaluation of BM, age and human epidermal growth factor receptor 2 (HER2) expression were significantly lower in the PD group than in the non-PD group (P<0.05). There were marked differences in CEA after therapy, the changes of CEA, and CA153 (∆-value) between the groups (P<0.05). The SUVmax and Ca concentration after therapy and ∆-value of SUVmax, along with the levels of CA153, CEA, and ALP, were valuable indicators for evaluating the efficacy of individual BMs (P<0.05). IHC of BM in the PD group showed differences compared to primary lesions, with antigen Ki-67 being downregulated in metastatic lesions and HER2 being downregulated in a portion of BMs (2 of 6). Meanwhile, the expression of estrogen receptor (ER) and progesterone receptor (PR) remained relatively unchanged. Conclusions: 18F-FDG PET/CT confers precise assessment of the posttreatment efficacy pertaining to BM in BC. This modality facilitates the identification of poor effect lesions following extant therapies and localization for pathological assessment and may substantially contribute to evaluating therapeutic efficacy, refining treatment strategies, and predicting the disease trajectory of patients with BC and BM.

Next-generation sequencing-based detection in a breast MMPMN patient with EGFR T790M mutation: a rare case report and literature review.

Multiple primary malignant neoplasms (MPMNs) are difficult to identify from the metastasis or recurrence of malignant tumors. Additionally, the genetic mutations in each primary tumor vary from each other; therefore, it is critical to explore potential abnormal genes. Next-generation sequencing (NGS) technology has emerged as a reliable approach for detecting mutated genes in primary tumors and can provide several targeted therapeutic options for patients with MPMNs. Here, we report a case of metachronous multiple primary malignant neoplasm (MMPMN) patient with primary ovarian and breast cancer. Targeted NGS genetic profiling revealed a rare EGFR T790M mutation in this patient's primary breast tumor tissue, which has only been reported previously in breast cancer (BC). Based on the NGS results, osimertinib was recommended for this patient. Although this patient did not receive osimertinib because of gastrointestinal hemorrhage, this case highlights the significance of NGS technology in the diagnosis and treatment of MPMNs.

Time-Related Vascular Inflammatory Response to COVID-19 Assessed by 18F-FDG PET/CT in Follow-Up Tumor Patients.

Purpose: This study aimed to assess COVID-19's effects on vascular inflammatory response, by evaluating 18-Fluorodeoxyglucose (18F-FDG) uptake via positron emission tomography/computed tomography (PET/CT) in the artery of diffuse large B cell lymphoma (DLBCL) patients before and after infection with COVID-19. Patients and Methods: Thirty-five DLBCL patients administered the chemotherapy regimen R-CHOP and examined by oncological 18F-FDG PET/CT imaging twice from August 2022 to February 2023 for pre-treatment evaluation or assessment of treatment efficacy were enrolled. Seventeen patients were confirmed with COVID-19 within the study period. Arterial wall FDG uptake was semi-quantitatively analyzed as TBR (target-to-blood pool ratio) in 14 different vascular regions using oncological 18F-FDG PET/CT. Based on COVID-19 course and the two PET/CT scans, we further analyzed time-related FDG uptake for vascular walls in DLBCL patients with COVID-19. Results: Arterial TBRs were higher in the last PET/CT examination than previous ones in all patients with or without COVID-19. Besides the ascending aorta, ΔTBR (last PET/CT scanning's TBR minus previous PET/CT scanning's TBR) were not significantly different between the COVID-19 and Control groups. However, cases scanned ≤30 days from infection had remarkably higher ΔTBRs in comparison with those assessed >30 days post-infection in the COVID-19 group (p<0.05). A moderate inverse correlation was observed between ∆Global TBR (last PET/CT scanning's average TBR value minus previous PET/CT scanning's average TBR value) and time distance from COVID-19 onset to 18F-FDG PET/CT scan (Spearman's rho=-0.591, P=0.012). Interestingly, there were no differences of changes of TBR between different purpose of PET/CT examination group. Conclusion: This work firstly suggested vascular inflammation is elevated in the early post-COVID-19 phase in DLBCL cases compared with prolonged post-COVID-19 phase or controls. Increasing attention should be paid to these patients and the protection of their vascular function and complications in early COVID-19.

Inflammatory Immune Process and Depression-like Behavior in Hypothyroid Rats: A [18F] DPA-714 Micro Positron Emission Tomography Study.

Hypothyroidism is closely related to mental disorders, mainly depression, through an as-yet-unknown mechanism. The cerebral inflammatory immune process has been implied to play a pivotal role in the onset of affective symptoms in several conditions. In order to gain insight into the mechanism underlying the depressive behaviors in hypothyroid rats, brain microglial activation was evaluated using micro positron emission tomography imaging with a translocator protein (TSPO) radioligand. Hypothyroidism was induced in adult male Wistar rats by administration of 0.05% propylthiouracil in drinking water for five weeks. Open field, forced swimming and tail suspension tests were employed to evaluate the depressive behavior in hypothyroid rats, and the relationship between the behavioral changes and brain microglial activation was evaluated using [18F] DPA-714 micro positron emission tomography imaging. The open field test revealed significantly reduced first-minute activity and rearing behavior in the hypothyroid group, as well as significantly increased immobility in the forced swimming test and the tail suspension test. Hypothyroidism induced significantly increased microglial activation in the hippocampus. The radioligand uptake in the hippocampus correlated negatively with first-minute activity in the open field test (p < 0.05), and the radioligand uptake in the hippocampus correlated positively with changes in the immobility time in the forced swimming test and the tail suspension test (p < 0.05). Immunohistochemistry also confirmed the activation of microglia and inflammatory bodies in hypothyroid rats. The results indicate that hypothyroidism can induce depressive behavior in adult Wistar rats, microglial activation in the hippocampus plays an important role in the depressive behavior in hypothyroid rats and the inflammatory immune mechanism may underlie the behavioral abnormalities in thyroid dysfunction. Furthermore, the findings in the present study suggest there might be a common mechanism underlying depressive behavior in adult-onset hypothyroidism and depression.

The differential diagnostic value of dual-phase 18F-DCFPyL PET/CT in prostate carcinoma.

OBJECTIVE: Binding of 18F-DCFPyL at prostate cancer (PC) cells increases over time. The dual-phase protocol may be helpful in separating benign lesions from malignant ones associated with prostate cancer. The purpose of this study was to retrospectively analyze the incremental diagnostic value of 18F-DCFPyL dual-time imaging in patients with prostate cancer. METHOD: 114 prostate-related malignant lesions and 43 benign lesions in 38 patients with prostate cancer were retrospectively analyzed. Maximum standardized uptake value (SUVmax) for benign and prostate-related malignant lesions were calculated at min 60 and min 120 of PET/CT imaging. In order to calculate SUV ratio, the SUVmax of left gluteus maximus was measured at the same time. The difference of SUVmax metrics and SUV ratio between malignant and benign lesions was statistically analyzed, the cut-off value of ROC curve was calculated, and the diagnostic efficacy of SUVmax index and SUV ratio at two time points was compared. RESULTS: SUVmax metrics and SUV ratio of early and delayed imaging of PC-related malignant lesions were significantly higher than those of benign lesions (p < 0.05). In terms of individual indicators, the highest accuracy and sensitivity was in the delayed SUV ratio (89.2% and 94.7%), the best specificity was in the early SUVmax (93.0%). When the individual and combined indicators were compared together, the SUV ratio in the delay period still showed the best diagnostic sensitivity and accuracy, and the best specificity were SUVmax early and ▵SUVmax, SUVmax early and RI. CONCLUSIONS: Uptake of 18F-DCFPyL increased over time in prostate-associated malignant lesions compared with benign tissue. For single-phase imaging, 2-hour (delayed) imaging has better diagnostic performance. However, the dual-phase imaging (1 and 2 h) are helpful in the differential diagnosis of prostate-associated malignant lesions and benign lesions.

Pseudoprogression after advanced first-line endocrine therapy in metastatic breast cancer with bone metastasis: A case report.

Approximately 75% of patients with advanced breast cancer develop bone metastasis, which significantly affects both the quality of life and the survival rate of patients. Accurate determination of the status of bone metastases is important for developing treatment strategies and the prognosis of the disease. Here, we report the case of a 33-year-old patient with advanced metastatic breast cancer (MBC) and multiple bone metastases, in which advanced first-line endocrine therapy and second-line chemotherapy were both considered unsuccessful according to the efficacy evaluation by conventional imaging. Considering the possibility of bone pseudoprogression, the original endocrine scheme was reapplied, and bone metastases achieved a great response of non-complete response (CR)/non-progressive disease (PD). This case showed that, in the course of therapy for the disease, if bone scintigraphy (BS) shows increased lesion density or new lesions, this probably indicates a favorable response (osteoblastic repair of osteolytic lesions) to therapy, and not the worsening of metastatic lesions, called bone pseudoprogression. This paper will provide new insights into strategies for the treatment of bone metastasis and shows the significance of distinguishing osteoblastic bone repair from real bone lesion progression in clinical settings.

Over-expression of Fgf8 in cardiac neural crest cells leads to persistent truncus arteriosus.

During cardiogenesis, the outflow tract undergoes a complicated morphogenesis, including the re-alignment of the great blood vessels, and the separation of aorta and pulmonary trunk. The deficiency of FGF8 in the morphogenesis of outflow tract has been well studied, however, the effect of over-dosed FGF8 on the development of outflow tract remains unknown. In this study, Rosa26R-Fgf8 knock-in allele was constitutively activated by Wnt1-cre transgene in the mouse neural crest cells presumptive for the endocardial cushion of outflow tract. Surprisingly, Wnt1-cre; Rosa26R-Fgf8 mouse embryos exhibited persistent truncus arteriosus and died prior to E15.5. The cardiac neural crest cells in Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus did not degenerate as in WT controls, but proliferated into a thickened endocardial cushion and then, blocked the blood outflow from cardiac chambers into the lungs, which resulted in the embryonic lethality. Although the spiral aorticopulmonary septum failed to form, the differentiaion of the endothelium and smooth muscle in the Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus were impacted little. However, lineage tracing assay showed that the neural crest derived cells aggregated in the cushion layer, but failed to differentiate into the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Further investigation displayed the reduced p-Akt and p-Erk immunostaining, and the decreased Bmp2 and Bmp4 transcription in the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Our findings suggested that Fgf8 over-expression in cardiac neural crest impaired the formation of aorticopulmonary septum by suppressing the endothelial differentiation and stimulating the proliferation of endocardial cushion cells, which implicated a novel etiology of persistent truncus arteriosus.

Genome-wide identification and expression analysis of the GSK gene family in Solanum tuberosum L. under abiotic stress and phytohormone treatments and functional characterization of StSK21 involvement in salt stress.

Plant Glycogen Synthase Kinase 3 (GSK3)/SHAGGY-like kinase (GSK) proteins play important roles in modulating growth, development, and stress responses in several plant species. However, little is known about the members of the potato GSK (StGSK) family. Here, nine StGSK genes were identified and phylogenetically grouped into four clades. Gene duplication analysis revealed that segmental duplication contributed to the expansion of the StGSK family. Gene structure and motif pattern analyses indicated that similar exon/intron and motif organizations were found in StGSKs from the same clade. Conserved motif and kinase activity analyses indicated that the StGSKs encode active protein kinases, and they were shown to be distributed throughout whole cells. Cis-acting regulatory element analysis revealed the presence of many growth-, hormone-, and stress-responsive elements within the promoter regions of the StGSKs, which is consistent with their expression in different organs, and their altered expression in response to hormone and stress treatments. Association network analysis indicated that various proteins, including two confirmed BES1 family transcription factors, potentially interact with StGSKs. Overexpression of StSK21 provides enhanced sensitivity to salt stress in Arabidopsis thaliana plants. Overall, these results reveal that StGSK proteins are active protein kinases with purported functions in regulating growth, development, and stress responses.

Single-Photon Emission Computed Tomography/Computed Tomography Image-Based Radiomics for Discriminating Vertebral Bone Metastases From Benign Bone Lesions in Patients With Tumors.

Purpose: The purpose of this study was to investigate the feasibility of Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) image-based radiomics in differentiating bone metastases from benign bone lesions in patients with tumors. Methods: A total of 192 lesions from 132 patients (134 in the training group, 58 in the validation group) diagnosed with vertebral bone metastases or benign bone lesions were enrolled. All images were evaluated and diagnosed independently by two physicians with more than 20 years of diagnostic experience for qualitative classification, the images were imported into MaZda software in Bitmap (BMP) format for feature extraction. All radiomics features were selected by least absolute shrinkage and selection operator (LASSO) regression and 10-fold cross-validation algorithms after the process of normalization and correlation analysis. Based on these selected features, two models were established: The CT model and SPECT model (radiomics features were derived from CT and SPECT images, respectively). In addition, a combination model (ComModel) combined CT and SPECT features was developed in order to better evaluate the predictive performance of radiomics models. Subsequently, the diagnostic performance between each model was separately evaluated by a confusion matrix. Results: There were 12, 13, and 18 features contained within the CT, SPECT, and ComModel, respectively. The constructed radiomics models based on SPECT/CT images to discriminate between bone metastases and benign bone lesions not only had high diagnostic efficacy in the training group (AUC of 0.894, 0.914, 0.951 for CT model, SPECT model, and ComModel, respectively), but also performed well in the validation group (AUC; 0.844, 0.871, 0.926). The AUC value of the human experts was 0.849 and 0.839 in the training and validation groups, respectively. Furthermore, both SPECT model and ComModel show higher classification performance than human experts in the training group (P = 0.021 and P = 0.001, respectively) and the validation group (P = 0.037 and P = 0.007, respectively). All models showed better diagnostic accuracy than human experts in the training group and the validation group. Conclusion: Radiomics derived from SPECT/CT images could effectively discriminate between bone metastases and benign bone lesions. This technique may be a new non-invasive way to help prevent unnecessary delays in diagnosis and a potential contribution in disease staging and treatment planning.

Modification of Serine 1040 of SIBRI1 Increases Fruit Yield by Enhancing Tolerance to Heat Stress in Tomato.

High temperature is a major environmental factor that adversely affects plant growth and production. SlBRI1 is a critical receptor in brassinosteroid signalling, and its phosphorylation sites have differential functions in plant growth and development. However, the roles of the phosphorylation sites of SIBRI1 in stress tolerance are unknown. In this study, we investigated the biological functions of the phosphorylation site serine 1040 (Ser-1040) of SlBRI1 in tomato. Phenotype analysis indicated that transgenic tomato harbouring SlBRI1 dephosphorylated at Ser-1040 showed increased tolerance to heat stress, exhibiting better plant growth and plant yield under high temperature than transgenic lines expressing SlBRI1 or SlBRI1 phosphorylated at Ser-1040. Biochemical and physiological analyses further showed that antioxidant activity, cell membrane integrity, osmo-protectant accumulation, photosynthesis and transcript levels of heat stress defence genes were all elevated in tomato plants harbouring SlBRI1 dephosphorylated at Ser-1040, and the autophosphorylation level of SlBRI1 was inhibited when SlBRI1 dephosphorylated at Ser-1040. Taken together, our results demonstrate that the phosphorylation site Ser-1040 of SlBRI1 affects heat tolerance, leading to improved plant growth and yield under high-temperature conditions. Our results also indicate the promise of phosphorylation site modification as an approach for protecting crop yields from high-temperature stress.

Subclinical Hypothyroidism after 131I-Treatment of Graves' Disease: A Risk Factor for Depression?

OBJECTIVES: Although it is well accepted that there is a close relationship between hypothyroidism and depression, previous studies provided inconsistent or even opposite results in whether subclinical hypothyroidism (SCH) increased the risk of depression. One possible reason is that the etiology of SCH in these studies was not clearly distinguished. We therefore investigated the relationship between SCH resulting from 131I treatment of Graves' disease and depression. DESIGN AND METHODS: The incidence of depression among 95 patients with SCH and 121 euthyroid patients following 131I treatment of Graves' disease was studied. The risk factors of depression were determined with multivariate logistic regression analysis. Thyroid hormone replacement therapy was performed in patients with thyroid-stimulating hormone (TSH) levels exceeding 10 mIU/L. RESULTS: Patients with SCH had significantly higher Hamilton Depression Scale scores, serum TSH and thyroid peroxidase antibody (TPOAb) levels compared with euthyroid patients. Multivariate logistic regression analysis revealed SCH, Graves' eye syndrome and high serum TPO antibody level as risk factors for depression. L-thyroxine treatment is beneficial for SCH patients with serum TSH levels exceeding 10 mIU/L. CONCLUSIONS: The results of the present study demonstrated that SCH is prevalent among 131I treated Graves' patients. SCH might increase the risk of developing depression. L-thyroxine replacement therapy helps to resolve depressive disorders in SCH patients with TSH > 10mIU/L. These data provide insight into the relationship between SCH and depression.