Clinical development of MRI-based multi-sequence multi-regional radiomics model to predict lymph node metastasis in rectal cancer.

OBJECTIVE: We aim to construct a magnetic resonance imaging (MRI)-based multi-sequence multi-regional radiomics model that will improve the preoperative prediction ability of lymph node metastasis (LNM) in T3 rectal cancer. METHODS: Multi-sequence MRI data from 190 patients with T3 rectal cancer were retrospectively analyzed, with 94 patients in the LNM group and 96 patients in the non-LNM group. The clinical factors, subjective imaging features, and the radiomic features of tumor and peritumoral mesorectum region of patients were extracted from T2WI and ADC images. Spearman's rank correlation coefficient, Mann-Whitney's U test, and the least absolute shrinkage and selection operator were used for feature selection and dimensionality reduction. Logistic regression was used to construct six models. The predictive performance of each model was evaluated by the receiver operating characteristic curve (ROC). The differences of each model were characterized by area under the curve (AUC) via the DeLong test. RESULTS: The AUCs of T2WI, ADC single-sequence radiomics model and multi-sequence radiomics model were 0.73, 0.75, and 0.78, respectively. The multi-sequence multi-regional radiomics model with improved performance was created by combining the radiomics characteristics of the peritumoral mesorectum region with the multi-sequence radiomics model (AUC, 0.87; p < 0.01). The AUC of the clinical model was 0.68, and the MRI-clinical composite evaluation model was obtained by incorporating the clinical data with the multi-sequence multi-regional radiomics features, with an AUC of 0.89. CONCLUSION: The MRI-based multi-sequence multi-regional radiomics model significantly improved the prediction ability of LNM for T3 rectal cancer and could be applied to guide surgical decision-making in patients with T3 rectal cancer.

Noradrenaline depresses facial stimulation-evoked cerebellar MLI-PC synaptic transmission via α2-AR/PKA signaling cascade in vivo in mice.

The noradrenergic fibers of the locus coeruleus, together with mossy fibers and climbing fibers, comprise the three types of cerebellar afferents that modulate the cerebellar neuronal circuit. We previously demonstrated that noradrenaline (NA) modulated synaptic transmission in the mouse cerebellar cortex via adrenergic receptors (ARs). In the present study, we investigated the effect of NA on facial stimulation-evoked cerebellar molecular layer interneuron (MLI)-Purkinje cell (PC) synaptic transmission in urethane-anesthetized mice using an in vivo cell-attached recording technique and a pharmacological method. MLI-PC synaptic transmission was induced by air-puff stimulation (duration: 60 ms) of the ipsilateral whisker pad, which exhibited positive components (P1 and P2) accompanied by a pause in simple spike activity. Cerebellar molecular layer application of NA (15 µM) decreased the amplitude and area under the curve of P1, and the pause in simple spike activity, but increased the P2/P1 ratio. The NA-induced decrease in P1 amplitude was concentration-dependent, and the half-inhibitory concentration was 10.94 µM. The NA-induced depression of facial stimulation-evoked MLI-PC GABAergic synaptic transmission was completely abolished by blockade of α-ARs or α2-ARs, but not by antagonism of α1-ARs or ß-ARs. Bath application of an α2-AR agonist inhibited MLI-PC synaptic transmission and attenuated the effect of NA on the synaptic response. NA-induced depression of MLI-PC synaptic transmission was completely blocked by a mixture of α2A- and 2B-AR antagonists, and was abolished by inhibition of protein kinase A. In addition, electrical stimulation of the molecular layer evoked MLI-PC GABAergic synaptic transmission in the presence of an AMPA receptor antagonist, which was inhibited by NA through α2-ARs. Our results indicate that NA inhibits MLI-PC GABAergic synaptic transmission by reducing GABA release via an α2-AR/PKA signaling pathway.

The diagnostic performance in clinically significant prostate cancer with PI-RADS version 2.1: simplified bpMRI versus standard mpMRI.

OBJECTIVES: To compare the diagnostic performance for the detection of clinically significant prostate cancer (csPCa) between bpMRI with only axial T2WI (simplified bpMRI) and standard-multiparametric MRI (mpMRI). METHODS: A total of 569 patients who underwent mpMRI followed by biopsy or prostatectomy were enrolled in this retrospective study. According to PI-RADS v2.1, three radiologists (A, B, C) from three centers blinded to clinical variables were assigned scores on lesions with simplified bpMRI and then with mpMRI 2 weeks later. Diagnostic performance of simplified bpMRI was compared with mpMRI using histopathology as reference standard. RESULTS: For all the three radiologists, the diagnostic sensitivity was significantly higher with mpMRI than with simplified bpMRI (P < 0.001 to P = 0.035); and although specificity was also higher with mpMRI than with simplified bpMRI for radiologist B and radiologist C, it was statistically significant only for radiologist B (P = 0.011, P = 0.359, respectively). On the contrary, for radiologist A, specificity was higher with simplified bpMRI than with mpMRI (P = 0.001). The area under the receiver operating characteristic curve (AUC) was significantly higher for mpMRI than for simplified bpMRI except for radiologist A (radiologist A: 0.903 vs 0.913, P = 0.1542; radiologist B: 0.861 vs 0.834 P = 0.0013; and radiologist C: 0.884 vs 0.848, P = 0.0003). Interobserver reliability of PI-RADS v2.1 showed good agreement for both simplified bpMRI (kappa = 0.665) and mpMRI (kappa = 0.739). CONCLUSION: Although the detection of csPCa with simplified bpMRI was comparatively lower than that with mpMRI, the diagnostic performance was still high in simplified bpMRI. Our data justify using mpMRI outperforms simplified bpMRI for prostate cancer screening and imply simplified bpMRI as a potential screening tool.

Analysis of the clinical efficacy and safety of computerized tomography-guided 125 I seed implantation in the treatment of non-small cell lung cancer that relapsed after chemoradiotherapy.

Purpose: The purpose is to evaluate the clinical efficacy and safety of computerized tomography (CT)-guided 125I seed implantation in the treatment of recurrent non-small cell lung cancer (NSCLC) after chemoradiotherapy. Materials and Methods: We retrospectively analyzed the data of 30 recurrent NSCLC patients in our institute from January 2016 to June 2020. According to the preoperative Treatment planning system plan, CT was used to guide 125I seed implantation into 30 evaluable lesions in the lungs. Clinical response rate, quality of life score, and adverse reactions were observed at postoperative follow-up. Results: The postoperative follow-up duration was 13 (1-24) months, of which the disease control rate at months one, three, and six were 96.67%, 93.1%, 85.18%, respectively and the objective response rate was 53.33%, 48.27%, and 48.14%, respectively. The postoperative 1-year and 2-year survival rates were 76.66% (23/30) and 53.33% (16/30), respectively. Median overall survival was 18 (1-24) months. The postoperative 1-year and 2-year progression-free survival (PFS) rates were 63.33% (19/30) and 40% (12/30), respectively. The median PFS was 14.5 (1-24) months. Adverse reactions include radiation-related pulmonary reactions in four patients (13.33%); skin reactions in four patients (13.33%); radiation-related esophageal reactions in two patients (6.67%), and leukopenia in three patients (10%). Other radiation-related adverse reactions did not occur. Conclusion: We conclude that 125I seed implantation is an effective and safe treatment for recurrent NSCLC.

The Antitumor Effect of Xihuang Pill on Treg Cells Decreased in Tumor Microenvironment of 4T1 Breast Tumor-Bearing Mice by PI3K/AKT~AP-1 Signaling Pathway.

To study the antitumor effect of Xihuang pill (XHP) on the number of Treg cells in the tumor microenvironment of 4T1 breast tumor-bearing mice by PI3K/AKT/AP-1 pathway, a mouse model was established. Flow cytometry (FCM) and immunohistochemistry (IHC) were used to detect the number of Treg cells in the tumor microenvironment; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect the apoptosis of Treg cells in tumor microenvironment. Quantitative real-time PCR (RT-qPCR) was used to detect the mRNA expression of PI3K, AKT, and AP-1 in Treg cells in tumor microenvironment; immunofluorescence (IF) and Western Blot (WB) were used to detect the protein expression of PI3K, AKT, and AP-1 in Treg cells in tumor microenvironment. Compared with the naive control group, the tumor weight in XHP groups decreased significantly (P < 0.05); FCM and IHC results showed that the number of Treg cells in the tumor microenvironment decreased with the dose of XHP groups (P < 0.05); TUNEL staining showed that the number of Treg cells in tumor microenvironment increased with the dose of XHP groups (P < 0.05); RT-qPCR results showed that the mRNA expression of PI3K and AKT in Treg cells decreased with the dose of XHP groups, while RNA expression of AP-1 increased with the dose of XHP groups (P < 0.05); IF and WB results showed that the protein expression of PI3K and AKT in Treg cells decreased with the dose of XHP groups and the protein expression of AP-1 increased with the dose of XHP groups (P < 0.05). The results suggested that XHP decreased the number of Treg cells via inhibiting PI3K and AKT expression and upregulating AP-1 expression in Treg cells and then promoting the apoptosis of Treg cells. Thus, XHP could improve the immunosuppressive state of tumor microenvironment and reverse the immune escape to inhibit tumor growth.

Xihuang pill promotes apoptosis of Treg cells in the tumor microenvironment in 4T1 mouse breast cancer by upregulating MEKK1/SEK1/JNK1/AP-1 pathway.

OBJECTIVE: To determine the role of the MEKK1/SEK1/JNK1/AP-1 pathway in the action of Xihuang pill (XHP) in reducing regulatory T (Treg) cell numbers in the tumor microenvironment in a 4T1 mouse breast cancer model, and to clarify the anti-tumor mechanism of XHP in breast cancer. METHODS: We established a mouse 4T1 breast cancer model. Model mice were administered XHP for 2 weeks, and tumor tissues were then removed, weighed, sliced, and homogenized. Treg cells in the tumor microenvironment were isolated by magnetic cell sorting and analyzed by immunohistochemistry and flow cytometry. Treg cell apoptosis was detected by TdT-mediated dUTP nick end labeling. mRNA expression levels of MEKK1, SEK1, JNK1, and AP-1 in Treg cells in the tumor microenvironment were detected by quantitative real-time PCR and their protein expression levels were detected by immunofluorescence staining and western blot. RESULTS: Tumor weights were significantly lower in the XHP groups compared with the untreated control group. The overall number of Treg cells in the tumor microenvironment decreased while the number of apoptotic Treg cells increased with increasing doses of XHP. mRNA and protein expression levels of MEKK1, SEK1, JNK1, and AP-1 in Treg cells in the tumor microenvironment increased with increasing doses of XHP. CONCLUSION: XHP might promote Treg cell apoptosis in the tumor microenvironment and further inhibit the tumor growth of 4T1 mouse breast cancer. The mechanism of XHP may be related to upregulation of gene and protein expression of MEKK1, SEK1, JNK1, and AP-1 in Treg cells in the tumor microenvironment.