BackgroundWe aimed to evaluate the diagnostic performance of 99mTc-MIBI SPECT/CT and ultrasonography in patients with secondary hyperparathyroidism (SHPT), and explored the factors that affect the diagnostic performance.Methods 99mTc-MIBI SPECT/CT and ultrasonography were performed in 50 patients with SHPT within 1 month before they underwent surgery. Imaging results were confirmed by the pathology. Pearson correlation analysis was used to determine the correlation of PTH level with clinical data. The optimal cutoff value for predicting positive 99mTc-MIBI results was evaluated by ROC analysis in lesions diameter.ResultsForty-nine patients had a positive 99mTc-MIBI imaging results and 39 patients had positive ultrasonography results. The sensitivities of 99mTc-MIBI and ultrasonography were 98.00% and 78.00%, respectively. A total of 199 lesions were resected in 50 patients. Among them, 183 lesions were proved to be parathyroid hyperplasia. On per-lesion basis analysis, the sensitivity and specificity of 99mTc-MIBI and ultrasonography were 59.34% and 75.00% vs 46.24% and 80.00%, respectively. The Pearson correlation analysis showed that the serum AKP and PTH level had a significant linear association (r = 0.699, P < 0.001). The lesion diameter was a statistically significant predictive factor in predicting positive 99mTc-MIBI SPECT/CT. The optimal cutoff value for predicting positive 99mTc-MIBI results evaluated by ROC analysis in lesions diameter was 8.05 mm.ConclusionDual phase 99mTc-MIBI SPECT/CT imaging had a higher sensitivity in patients with SHPT than ultrasonography. Therefore, using 99mTc-MIBI positioning the lesion could be an effective method pre-surgical in patients with SHPT.

Oncogenic activation of KRAS and its surrogates is essential for tumour cell proliferation and survival, as well as for the development of protumourigenic microenvironments. Here, we show that the deubiquitinase USP12 is commonly downregulated in the KrasG12D-driven mouse lung tumour and human non-small cell lung cancer owing to the activation of AKT-mTOR signalling. Downregulation of USP12 promotes lung tumour growth and fosters an immunosuppressive microenvironment with increased macrophage recruitment, hypervascularization, and reduced T cell activation. Mechanistically, USP12 downregulation creates a tumour-promoting secretome resulting from insufficient PPM1B deubiquitination that causes NF-κB hyperactivation in tumour cells. Furthermore, USP12 inhibition desensitizes mouse lung tumour cells to anti-PD-1 immunotherapy. Thus, our findings propose a critical component downstream of the oncogenic signalling pathways in the modulation of tumour-immune cell interactions and tumour response to immune checkpoint blockade therapy.

Dual-energy spectral computed tomography (DeSct) is based on fast switching between high and lowvoltages from view to view to obtain dual-energy imaging data, and it can generate monochromatic image sets, iodine-based material decomposition images and spectral ct curves. Quantitative spectral CT parameters may be valuable for reflecting Ki-67 expression and EGFR mutation status in nonsmall-cell lung cancer (nScLc). We investigated the associations among the quantitative parameters generated in DESCT and Ki-67 expression and EGFR mutation in NSCLC. We studied sixty-five NSCLC patients with preoperative DESCT scans, and their specimens underwent Ki-67 and EGFR evaluations. Statistical analyses were performed to identify the spectral CT parameters for the diagnosis of Ki-67 expression and EGFR mutation status. We found that tumour grade and the slope of the spectral CT curve in the venous phase were the independent factors influencing the Ki-67 expression level, and the area under the curve (AUc) of the slope of the spectral ct curve in the venous phase in the receiver operating characteristic analysis for distinguishing different Ki-67 expression levels was 0.901. Smoking status and the normalized iodine concentration in the venous phase were independent factors influencing EGFR mutation, and the AUC of the two-factor combination for predicting the presence of EGFR mutation was 0.807. These results show that spectral CT parameters may be useful for predicting Ki-67 expression and the presence of EGFR mutation in NSCLC.Lung cancer is one of the most common causes of cancer death worldwide 1 , and non-small-cell lung cancer (NSCLC) is the most common pathological type. Many NSCLC patients suffer from recurrence after treatment, and treatment outcomes varied among patients with advanced disease. Currently, several predictive factors, such as histological subtypes or biomarkers, including Ki-67 and epidermal growth factor receptor (EGFR), have shown important clinical value in the treatment and prognosis of NSCLC patients.Ki-67 is a nuclear protein that is expressed during all active phases of the cell cycle but is absent in G0. Thus, it is regarded as a cellular proliferation marker 2,3 . It has predictive value for the clinical course of various cancers, e.g., invasiveness, treatment response, recurrence and survival 4-7 . Regarding NSCLC, Ki-67 has also been recognized as a common biological marker in the evaluation of lung cancer and has been shown to have great potential as an important prognostic factor 8-10 . Analysis of Ki-67 in resected NSCLC tissues suggests that patients with high Ki-67 values may have a more negative prognosis and a high risk of recurrence, and Ki-67 can also predict survival after treatment 8,11,12 . In clinical practice, patients with EGFR mutations can be selected for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) for their sensitivity to EGFR-TKIs, and this treatment results in long survival, enhanced quality of life and decreased treatment-related side effects [13][14][15] ...