Abstract Objective Rab11A is an important molecule for recycling endosomes and is closely related to the proliferation, invasion, and metastasis of tumors. This study investigated the prognostic and immune significance of Rab11A and validated its potential function and mechanism in breast cancer (BRCA). Methods RNA sequencing data for 33 tumors were downloaded from The Cancer Genome Atlas (TCGA) and Genotype‐Tissue Expression databases. Correlation analysis was used to evaluate the relationship between Rab11A expression and immune characteristics. Potential pathways were identified using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis. Immunohistochemical analysis, colony formation assay, bromodeoxyuridine incorporation assay, immunofluorescence, and Western blot were used to explore potential function and mechanism. Results Analysis of the TCGA database showed significant upregulation of Rab11A expression in a variety of cancers. Rab11A was up‐regulated in 82.4% of BRCA. High Rab11A expression is associated with poor survival in cancer patients and is a predictor of poor prognosis. CIBERSORT analysis showed that Rab11A was negatively associated with almost all immune cycle activity scores pan‐cancer. The results of the TCGA‐BRCA cohort were further confirmed by using pathological samples from clinical BRCA patients. The results showed that Rab11A expression was correlated with estrogen receptor (ER) and progesterone receptor expression in BRCA ( p < 0.05). Knockdown and overexpression of Rab11A affected the proliferation of BRCA cells. Further mechanistic studies revealed that down‐regulation of ER alpha (ERα) and up‐regulation of ER beta (ERβ) mediated Rab11A‐induced inhibition of BRCA cell proliferation. Conclusion Rab11A expression in pan‐cancer is associated with poor prognosis and immune profile. In particular, in BRCA, Rab11A expression regulates cell proliferation by targeting ERα and ERβ. High Rab11A expression is tightly associated with immune characteristics, tumor microenvironment, and genetic mutations. These results provide a reference for exploring the role of Rab11A in pan‐cancer and provide a new perspective for revealing potential therapeutic targets in BRCA.
Existing self-supervised learning methods based on contrastive learning and masked image modeling have demonstrated impressive performances. However, current masked image modeling methods are mainly utilized in natural images, and their applications in medical images are relatively lacking. Besides, their fixed high masking strategy limits the upper bound of conditional mutual information, and the gradient noise is considerable, making less the learned representation information. Motivated by these limitations, in this paper, we propose masked patches selection and adaptive masking strategy based self-supervised medical image segmentation method, named MPS-AMS. We leverage the masked patches selection strategy to choose masked patches with lesions to obtain more lesion representation information, and the adaptive masking strategy is utilized to help learn more mutual information and improve performance further. Extensive experiments on three public medical image segmentation datasets (BUSI, Hecktor, and Brats2018) show that our proposed method greatly outperforms the state-of-the-art self-supervised baselines.
Objective:To establish the normative value of motor unit action potentials(MUAP) of rectus abdominis muscles. Methods:The standard EMG was recorded from rectus abdominis muscles including duration,amplitude and percentage of polyphasic waves of MUAP in 109 normative subjects. Results: The normative value of MUAP of rectus abdominis muscles were:amplitude 373. 78 ± 56. 46μV,duration 9.95±1.13ms,polyphasic waves 19. 40 ±4.52% respectively. Conclusions:Parameters of EMG of rectus abdominis muscle can be detected reliably and are helpful for the diagnosis of lesion in lower motor neuron involved in the thoracic region.
Abstract Aim Exosomes has been shown to be involved in the regulation of cancer progression. However, the role of exosome miR‐134‐5p in breast cancer (BC) progression is unclear. Methods Exosomes were extracted from BC cells (MCF‐7 and MDA‐MB‐231) using differential centrifugation and were observed by transmission electron microscope (TEM). The protein levels of exosome markers, apoptosis markers, Rho GTPase activating protein 1 (ARHGAP1, an important oncogene in BC) and phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) markers were detected by western blot (WB) assay. Quantitative real‐time PCR was used to measure the expression levels of miR‐134‐5p and ARHGAP1. Cell cycle and apoptosis, colony number, viability, migration, and invasion were determined by flow cytometry, colony formation assay, MTT assay, and transwell assay, respectively. The interaction between miR‐134‐5p and ARHGAP1 was confirmed using a dual‐luciferase reporter assay. Xenograft models were constructed to verify the role of exosome miR‐134‐5p in BC tumor growth in vivo. Results MiR‐134‐5p was lowly expressed in BC cells and in the exosomes of BC cells. Overexpressed exosome miR‐134‐5p suppressed the proliferation, migration, invasion, and promoted the apoptosis of BC cells. ARHGAP1 was a target of miR‐134‐5p, and its silencing could inhibit BC progression. In addition, ARHGAP1 overexpression could reverse the negative regulation of miR‐134‐5p on BC progression. MiR‐134‐5p could target ARHGAP1 to inhibit the activity of PI3K/AKT pathway. Exosome miR‐134‐5p overexpression could suppress BC tumor growth via targeting ARHGAP1 in vivo. Conclusion Exosome miR‐134‐5p restrained BC progression through regulating ARHGAP1/PI3K/AKT signaling pathway, suggesting that miR‐134‐5p might be a therapeutic target for BC.
e12604 Background: Neoadjuvant therapy plays an important role in improving the clinical efficacy for patients with stage II-III epidermal growth factor receptor 2 (HER2)-positive breast cancer. Pyrotinib, a new irreversible tyrosine kinase inhibitor (TKI), combined with capecitabine have demonstrated a promising anti-tumour activity in metastatic breast cancer. Here, we conducted a multicenter, randomized, phase II, open-label trial aiming exploring the outcomes of adding pyrotinib to EC-TH neoadjuvant therapy. Methods: Patients aged 18–65 years old with invasive carcinoma, cT1-4N0-3M0 stage, HER2-positive breast cancer were enrolled. Cases were randomly assigned into neoadjuvant therapy with four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (or Paclitaxel for Injection, albumin bound) and trastuzumab (EC-TH), or pyrotinib (400mg day 1-21) combined with EC-TH. Results: 56 patients had completed 8 cycles of neoadjuvant therapy (40 in the treatment group and 16 in the controlled group). 20 patients underwent radical surgery after neoadjuvant therapy. Compared with EC-TH along (37.5%, 3/8), the addition of pyrotinib to EC-TH neoadjuvant chemotherapy (py+EC-TH) significantly increased the pathological complete response (pCR)rate (75%, 9/12) in patients with HER2-positive breast cancer. The objective response rate (ORR) was 87.5% (7/8) vs 100% (12/12) . The most common adverse effects (AEs) in the treatment group was diarrhoea with grade 3 occurred in 3 cases (7.5% 3/40), which most limited in the first treatment cycle. No grade 3 diarrhoea was observed in controlled group. Other AEs including leukopenia occurred similarly in both groups and no cardiovascular dysfunction was observed. Conclusions: Pyrotinib added to EC-TH neoadjuvant therapy significantly increased the pCR rate, suggesting an applicable strategy for HER2-positive breast cancer. Clinical trial information: NCT04290793.
To evaluate a novel real-time phase-contrast magnetic resonance imaging (MRI) technique for the assessment of through-plane flow in the ascending aorta.Real-time MRI was based on a radial fast low-angle shot (FLASH) sequence with about 30-fold undersampling and image reconstruction by regularized nonlinear inversion. Phase-contrast maps were obtained from two (interleaved or sequential) acquisitions with and without a bipolar velocity-encoding gradient. Blood flow in the ascending aorta was studied in 10 healthy volunteers at 3 T by both real-time MRI (15 sec during free breathing) and electrocardiogram (ECG)-synchronized cine MRI (with and without breath holding). Flow velocities and stroke volumes were evaluated using standard postprocessing software.The total acquisition time for a pair of phase-contrast images was 40.0 msec (TR/TE = 2.86/1.93 msec, 10° flip angle, 7 spokes per image) for a nominal in-plane resolution of 1.3 mm and a section thickness of 6 mm. Quantitative evaluations of spatially averaged flow velocities and stroke volumes were comparable for real-time and cine methods when real-time MRI data were averaged across heartbeats. For individual heartbeats real-time phase-contrast MRI resulted in higher peak velocities for values above 120 cm s(-1).Real-time phase-contrast MRI of blood flow in the human aorta yields functional parameters for individual heartbeats. When averaged across heartbeats real-time flow velocities and stroke volumes are comparable to values obtained by conventional cine MRI.
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