StatementThis prospective longitudinal study systematically described the temporal changes of CT findings in COVID-19 pneumonia and summarized the CT findings at the time of hospital discharge. Key ResultsThe extent of CT abnormalities progressed rapidly after symptom onset, peaked during illness days 6-11, and followed by persistence of high levels.The predominant pattern of abnormalities after symptom onset was ground-glass opacity; the percentage of mixed pattern peaked during illness days 12-17, and became the second most prevalent pattern thereafter.Sixty-six of the 70 patients (94%) discharged had residual disease on final CT scans, with ground-glass opacity the most common pattern. Abbreviations: COVID-19: corona virus disease 2019 SARS-CoV-2: severe acute respiratory syndrome coronavirus 2 rRT-PCR: real-time reverse transcriptase-polymerase chain reaction I n P r e s s Abstract Background: CT may play a central role in the diagnosis and management of COVID-19 pneumonia.Purpose: To perform a longitudinal study to analyze the serial CT findings over time in patients with COVID-19 pneumonia. Materials and Methods:During January 16 to February 17, 2020, 90 patients (male:female, 33:57; mean age, 45 years) with COVID-19 pneumonia were prospectively enrolled and followed up until they were discharged or died, or until the end of the study. A total of 366 CT scans were acquired and reviewed by 2 groups of radiologists for the patterns and distribution of lung abnormalities, total CT scores and number of zones involved. Those features were analyzed for temporal change.Results: CT scores and number of zones involved progressed rapidly, peaked during illness days 6-11 (median: 5 and 5), and followed by persistence of high levels. The predominant pattern of abnormalities after symptom onset was ground-glass opacity (35/78 [45%] to 49/79 [62%] in different periods). The percentage of mixed pattern peaked (30/78 [38%]) on illness days 12-17, and became the second most predominant pattern thereafter. Pure ground-glass opacity was the most prevalent sub-type of groundglass opacity after symptom onset (20/50 [40%] to 20/28 [71%]). The percentage of ground-glass opacity with irregular linear opacity peaked on illness days 6-11 (14/50 [28%)]) and became the second most prevalent subtype thereafter. The distribution of lesions was predominantly bilateral and subpleural. 66/70 (94%) patients discharged had residual disease on final CT scans (median CT scores and zones involved: 4 and 4), with ground-glass opacity (42/70 [60%]) and pure ground-glass opacity (31/42 [74%]) the most common pattern and subtype. Conclusion:The extent of lung abnormalities on CT peaked during illness days 6-11. The temporal changes of the diverse CT manifestations followed a specific pattern, which might indicate the progression and recovery of the illness.
Ischaemic stroke is becoming the most common cerebral disease in aging populations, but the underlying molecular mechanism of the disease has not yet been fully elucidated. Increasing evidence has indicated that an excess of iron contributes to brain damage in cerebral ischaemia/reperfusion (I/R) injury. Although mitochondrial ferritin (FtMt) plays a critical role in iron homeostasis, the molecular function of FtMt in I/R remains unknown. We herein report that FtMt levels are upregulated in the ischaemic brains of mice. Mice lacking FtMt experience more severe brain damage and neurological deficits, accompanied by typical molecular features of ferroptosis, including increased lipid peroxidation and disturbed glutathione (GSH) after cerebral I/R. Conversely, FtMt overexpression reverses these changes. Further investigation shows that Ftmt ablation promotes I/R-induced inflammation and hepcidin-mediated decreases in ferroportin1, thus markedly increasing total and chelatable iron. The elevated iron consequently facilitates ferroptosis in the brain of I/R. In brief, our results provide evidence that FtMt plays a critical role in protecting against cerebral I/R-induced ferroptosis and subsequent brain damage, thus providing a new potential target for the treatment/prevention of ischaemic stroke.
Background: Immunotherapies targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have been approved for gastric cancer (GC) patients. However, a large proportion of patients with T-cell-inflamed tumor microenvironment do not respond to the PD-1/PD-L1 blockade. The stromal component of the tumor microenvironment has been associated with immunotherapy. This study aims to explore the clinical significance of the nonimmune cells in the tumor microenvironment and their potential as biomarkers for immunotherapy. Methods: A total of 383 patients with GC from the Cancer Genome Atlas (TCGA) cohort, 300 patients with GC from the GSE62254 cohort in Gene Expression Omnibus (GEO) were included in the study. A stromal score was generated using the ESTIMATE algorithm, and the likelihood of response to PD-1/PD-L1 immunotherapy of GC patients was predicted using the TIDE algorithm. The prognostic value of the stromal score from GC cases was evaluated by the Kaplan-Meier method and Cox regression analysis. Gene set enrichment analysis (GSEA) was also conducted. Results: The stromal score showed significant differences in different molecular subtypes and T stages. Multivariate analyses further confirmed that the stromal score was an independent indicator of overall survival (OS) in the two cohorts. The low stromal score group showed higher tumor mutation burden (TMB) and micro-satellite instability (MSI), and was more sensitive to immune checkpoint inhibitor according to the TIDE algorithm. Activation of the transforming growth factor and epithelial-mesenchymal transition were observed in the high stromal score subtype, which is associated with T-cell suppression, and may be responsible for resistance to PD-1/PD-L1 therapy. BPIFB2 was confirmed as a hub gene relevant to immunotherapy. Conclusion: The stromal score was associated with cancer progression and molecular subtypes, and may serve as a novel biomarker for predicting the prognosis and response to immunotherapy in patients with GC.
We aimed to determine whether Neuropilin-1 (NRP1) promotes gastric cancer (GC) metastasis by inducing epithelial-mesenchymal transition (EMT), and to clarify its regulatory mechanism. Using the data of GC patients in The Cancer Genome Atlas (TCGA) and Gene Tissue Expression (GTEx) databases, combined with the data of GC patients in our medical center, the effect of NRP1 on the prognosis of GC patients were analyzed. Then, we investigated the role of NRP1 in GC metastasis and its potential mechanism. The level of NRP1 was up-regulated in GC tissues and associated with poor prognosis of GC patients. The expression of NRP1 was closely related to maximum tumor diameter, invasion depth, lymphnode metastasis, distant metastasis, and advanced TNM stage, and was an independent prognostic factor for overall survival (OS) in GC patients. Besides, the results of in vitro indicated that NRP1 could induce EMT to promote the migration and invasion of GC cells by activating PI3K/Akt signaling pathway, and the HGF/c-Met axis was involved in this process. This study determined that NRP1 was a gene that promotes gastric cancer. NRP1 induced EMT to enhance the migration and invasion ability of GC cells by activating PI3K/Akt signaling pathway. NRP1 was an independent prognostic marker for OS in GC patients and expected to be a therapeutic target for GC patients.
The immunomodulatory activity of a few Lactobacillus exopolysaccharides (EPS) has been reported. However, whether Lactobacillus EPS can promote the differentiation of CD4 T lymphocytes (CD4+T) cells into T-helper 17 cells (Th17 cells) in the Peyer’s Patches (PPs) of mice has not been addressed. In this study, we found the molecular weight (M w) of the purified EPS from L. casei ranged from 2.7 × 106 Da to 1.7 × 107 Da, and the average M w was approximately 8.4 × 106 Da. In healthy BALB/c mice, EPS elevated the numbers of Th17 cells and levels of Th17-related cytokines. In vitro, EPS induced BMDCs to stimulate the differentiation of CD4+T cells of PPs into Th17 cells and the related cytokine secretions. Results suggest that L. casei EPS can effectively induce and promote the differentiation of CD4+T cells of PPs into Th17 cells in healthy mice and has the potential ability to improve intestinal mucosa immunity.
Objective: To investigate the incidence and risk factors for liver abscess formation after treatment with drug-eluting bead chemoembolization (DEB-TACE) in patients with metastatic hepatic tumors (MHT). Methods: The current study is a retrospective analysis of the clinical data of 137 patients with metastatic hepatic tumors who received DEB-TACE treatment in our institute (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) between June 2015 and September 2020. Patients were evaluated for the presence or absence of post-DEB-TACE liver abscess. Univariate and multivariate analyses were used to identify risk factors for liver abscess formation. Results: The incidence of liver abscess formation after the DEB-TACE procedure was 8.76% per patient and 5.53% per procedure. Univariate analysis showed that larger maximum tumor diameter (p = 0.004), Grade 1 artery occlusion (p < 0.001) and systemic chemotherapy within 3 months before the DEB-TACE procedure (p < 0.001) were all associated with liver abscess formation. However, only systemic chemotherapy within 3 months before the DEB-TACE procedure (OR 5.49; 95% CI 0.34–13.54; p < 0.001) was identified by multivariate analysis to be an independent risk factor. Conclusions: Tumor size, Grade 1 artery occlusion and recent systemic chemotherapy may all be associated with increased risk of liver abscess formation following DEB-TACE treatment in patients with metastatic hepatic tumors. Advances in knowledge: Identification of risk factors for liver abscess formation following DEB-TACE in patients with MHT. These findings suggest the need for caution and consideration of the aforementioned risk factors on the part of interventional radiologists when designing DEB-TACE strategies and performing post-procedure patient management.
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