Alpinetin ameliorates bleomycin-induced pulmonary fibrosis by repressing fibroblast differentiation and proliferation.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with a poor prognosis. Alpinetin (ALP), derived from Alpinia katsumadai Hayata, has shown potential as a therapeutic measure of various diseases. However, the utilization of ALP in managing pulmonary fibrosis and its underlying mechanisms are still not fully understood. METHODS: A well-established mouse model of pulmonary fibrosis induced by bleomycin (BLM) was used in this study. The antifibrotic effects of ALP on histopathologic manifestations and expression levels of fibrotic markers were examined. Subsequently, the impact of ALP on fibroblast differentiation, proliferation, apoptosis, and associated signaling pathways was investigated to elucidate the underlying mechanisms. RESULTS: In the present study, we observed that ALP effectively mitigated BLM-induced pulmonary fibrosis in mice, as evidenced by histopathological manifestations and the expression levels of fibrotic markers. Furthermore, the in vitro experiments demonstrated that ALP treatment attenuated the ability of fibroblasts to differentiate into myofibroblasts. Mechanically, our findings provided evidence that ALP suppressed fibroblast-to-myofibroblast differentiation by repressing TGF-ß/ALK5/Smad signaling pathway. ALP was found to possess the capability of inhibiting fibroblast proliferation and promoting apoptosis of fibroblasts induced by TGF-ß. CONCLUSION: In general, ALP may exert therapeutic effects on pulmonary fibrosis by modulating the differentiation, proliferation, and apoptosis of fibroblasts. Although its safety has been demonstrated in mice, further studies are required to investigate the efficacy of ALP in treatment of patients with IPF.

Radiological assessment of immunotherapy effects and immune checkpoint-related pneumonitis for lung cancer.

Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life-threatening immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI-pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X-ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI-pneumonitis. Additionally, it is tried to differentiate ICI-pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID-19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help.

Accelerated three-dimensional susceptibility weighted imaging of the whole spine of fetus at 3T.

OBJECTIVES: To investigate the image quality and capability of generalized auto-calibrating partially parallel acquisition (GRAPPA) accelerated Three-dimensional (3D) susceptibility weighted imaging (SWI) of the whole spine at 3T. METHODS: A total of 37 pregnant women (gestation age 22 to 39 weeks, average 29 ± 3 weeks) with suspected fetal vertebral anomalies by ultrasound (US) screening underwent 3.0T MR imaging with 3D SWI, conventional two-dimensional (2D) half-flourier acquisition single-shot turbo spin-echo (HASTE) and 3D true fast imaging with steady-state precession (True FISP). The acquisition time of each protocol was recorded. Signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were determined in representative interest regions of fetal thoracic vertebrae and compared among three pulse sequences. Two radiologists rated image quality independently in random order on a 5-point scale. Kappa coefficients were computed to assess inter-observer reliability. Receiver operating characteristic curves were generated, and the area under the curve (AUC) was used to compare the diagnostic performance of each protocol in vertebral deformities. RESULTS: The acquisition time was 15 s for 3D-SWI and 17 s for 3D True FISP, significantly shorter than conventional HASTE (37 s; both P < 0.01). Of the three protocols, The SNR was highest on 3D True FISP, while the CNR was highest on 3D SWI. Visualization of all segments of the whole spine by 3D SWI was comparable with 3D True FISP. In contrast, 3D SWI and 3D True FISP depicted cervical and sacrococcygeal vertebrae better than HASTE. The weighted kappa statistic was 0.70-0.89 to evaluate the image quality of all segments of the whole spine, indicating good to excellent interobserver agreement. 3D SWI had the highest diagnostic performance for detecting fetal vertebral anomalies (AUC = 0.92). CONCLUSIONS: 3D-SWI is feasible for improved visualization of the whole fetal vertebral column and its congenital malformations with adequate image quality and high accuracy, thereby providing a supplementary method to conventional MR imaging.

The efficacy and safety of tacrolimus on top of glucocorticoids in the management of IIM-ILD: A retrospective and prospective study.

Objective: To examine the efficacy of tacrolimus on top of glucocorticoids (GCs) in the management of idiopathic inflammatory myopathies-associated interstitial lung disease (IIM-ILD) and further assess the therapeutic benefit and safety of low-dose pirfenidone followed above treatments. Methods: The retrospective study comprised 250 patients with IIM-ILD hospitalized in Tongji Hospital from 2014 to 2020. Demographic data, survival outcomes, and recurrence rates over the 1-year follow-up period were retrospectively analyzed. These patients were divided into two groups based on treatment with tacrolimus alone or other conventional immunosuppressants. Endpoints were compared by adjusted Cox regression model using inverse probability of treatment weighting to minimize treatment bias and potential confounders. For the prospective study, IIM-ILD patients treated with tacrolimus alone or tacrolimus combined with low-dose pirfenidone were enrolled from 2018 to 2020. Clinical characteristics, survival outcomes and multifarious assessment scales were followed up at baseline, 3, 6 and 12 months. The primary endpoint was 12-month survival rate and the secondary endpoints included respiratory-related events, adverse events, exacerbation in HRCT findings and laboratory parameters during therapy courses, and changes in respiratory function. Results: For the retrospective study, tacrolimus group (n=93) had a significantly higher survival rate (weighted HR=0.330, p=0.002) and a lower relapse rate (weighted HR=0.548, p=0.003) compared with patients treated with other types of immunosuppressant (n=157) after adjustment. The prospectively enrolled 34 IIM-ILD patients were treated with tacrolimus (n=12) or tacrolimus combined with low-dose pirfenidone (n=22). After 12 months of treatment with tacrolimus, patients in the prospective cohort showed significant improvements in cardio-pulmonary function, disease activity, muscle strength, and mental scale from baseline. Subgroup analysis indicated that patients with tacrolimus and pirfenidone combination therapy showed lower chest HRCT scores (p=0.021) and lower respiratory-related relapse rates than those in tacrolimus monotherapy group (log-rank p=0.0029). The incidence rate of drug-associated adverse events (AEs) was comparable between two groups and none of the patients discontinued the treatment due to severe AEs. Conclusion: Tacrolimus is well-tolerated and effective in the treatment of IIM-ILD. Furthermore, low-dose pirfenidone add-on treatment seems result in favorable improvements in pulmonary involvements for IIM-ILD patients. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2100043595.

CircSPI1_005 ameliorates osteoarthritis by sponging miR-370-3p to regulate the expression of MAP3K9.

BACKGROUND: Osteoarthritis (OA), caused by the destruction of joint cartilage, is the most prevalent form of arthritis, causing pain and stiffness in joints among millions of patients worldwide. Increasing evidence suggests that non-coding RNAs, including circular RNAs, play important roles in the pathogenesis of OA, but the precise signaling pathway is still unclear. METHODS: To study OA, we established a mouse model by the destabilized medial meniscus (DMM) surgery and used IL-1ß stimulated human cell line C28/I2 as an in vitro study. To further study the role of circSPI1_005 in regulating cell proliferation and apoptosis, EdU staining and FACS-based (fluorescence-activated cell sorting) apoptosis examination were performed after the manipulation of the expression of circSPI1_005. Also, bioinformatics predictions were conducted to analyze the downstream microRNAs of circSPI1_005 and the protein regulated by circSPI1_005. The luciferase assay and the RNA immunoprecipitation (RIP) assay were used to confirm the binding between circSPI1_005 and the predicted microRNA. To verify the role of circSPI1_005 in regulating OA in vivo, we also over-expressed circSPI1_005 by injecting AAV into previously injured knees to improve the OA symptoms. RESULTS: In this study, we found that circSPI1_005 was significantly down-regulated in IL-1ß treated chondrocyte cell lines and cartilage tissues of the OA mouse model. Overexpression of circSPI1_005 ameliorated OA by increasing proliferation and inhibiting apoptosis, and knockdown of circSPI1_005 in chondrocytes mimicked OA phenotypes. Bioinformatics study showed circSPI1_005 could sponge to miR-370-3p, and mechanistic studies confirmed the functional binding between circSPI1_005 and miR-370-3p. Furthermore, we conducted a TargetScan analysis and found that MAP3K9 (mitogen-activated protein kinase kinase kinase 9) could be the downstream protein effector. The expression level of MAP3K9 was regulated by miR-370-3p and overexpression of MAP3K9 could efficiently ameliorate OA. Also, we over-expressed circSPI1_005 in vivo and found that the cartilage surface in the OA mouse model was improved with overexpression of circSPI1_005. CONCLUSIONS: Collectively, circSPI1_005 could sponge to miR-370-3p to regulate the expression of MAP3K9, ameliorating the progression of osteoarthritis.

Construction of a predictive model for immunotherapy efficacy in lung squamous cell carcinoma based on the degree of tumor-infiltrating immune cells and molecular typing.

BACKGROUND: To construct a predictive model of immunotherapy efficacy for patients with lung squamous cell carcinoma (LUSC) based on the degree of tumor-infiltrating immune cells (TIIC) in the tumor microenvironment (TME). METHODS: The data of 501 patients with LUSC in the TCGA database were used as a training set, and grouped using non-negative matrix factorization (NMF) based on the degree of TIIC assessed by single-sample gene set enrichment analysis (GSEA). Two data sets (GSE126044 and GSE135222) were used as validation sets. Genes screened for modeling by least absolute shrinkage and selection operator (LASSO) regression and used to construct a model based on immunophenotyping score (IPTS). RNA extraction and qPCR were performed to validate the prognostic value of IPTS in our independent LUSC cohort. The receiver operating characteristic (ROC) curve was constructed to determine the predictive value of the immune efficacy. Kaplan-Meier survival curve analysis was performed to evaluate the prognostic predictive ability. Correlation analysis and enrichment analysis were used to explore the potential mechanism of IPTS molecular typing involved in predicting the immunotherapy efficacy for patients with LUSC. RESULTS: The training set was divided into a low immune cell infiltration type (C1) and a high immune cell infiltration type (C2) by NMF typing, and the IPTS molecular typing based on the 17-gene model could replace the results of the NMF typing. The area under the ROC curve (AUC) was 0.82. In both validation sets, the IPTS of patients who responded to immunotherapy were significantly higher than those who did not respond to immunotherapy (P = 0.0032 and P = 0.0451), whereas the AUC was 0.95 (95% CI = 1.00-0.84) and 0.77 (95% CI = 0.58-0.96), respectively. In our independent cohort, we validated its ability to predict the response to cancer immunotherapy, for the AUC was 0.88 (95% CI = 1.00-0.66). GSEA suggested that the high IPTS group was mainly involved in immune-related signaling pathways. CONCLUSIONS: IPTS molecular typing based on the degree of TIIC in the TME could well predict the efficacy of immunotherapy in patients with LUSC with a certain prognostic value.

Application of computer-aided detection (CAD) software to automatically detect nodules under SDCT and LDCT scans with different parameters.

PURPOSE: To explore the application of computer-aided detection (CAD) software on automatically detecting nodules under standard-dose CT (SDCT) and low-dose CT (LDCT) scans with different parameters including definition modes and blending levels of adaptive statistical iterative reconstruction (ASIR), whose influence was important to optimize radiology workflow serving for clinical work. MATERIALS AND METHODS: 117 patients underwent SDCT and LDCT scans. The comprehensive performance of CAD in detect pulmonary nodules including under different ASIR blending levels (0%, 60%, and 80%) and high-definition (HD) or non-HD modes were assessed. The true positive (TP) rate, false positive (FP) rate and the sensitivity were recorded. RESULTS: The stand-alone sensitivity of CAD system was 78.03% (515/660) in SDCT images and 70.15% (456/650) on LDCT images (p < 0.05). The sensitivity of CAD system to pulmonary nodules under non-HD mode was higher than that under HD mode. The detectability of nodules in images reconstructed with 60% and 80% ASIR was found significantly superior to that with 0% ASIR (p < 0.001). The overall sensitivity of CAD system on LDCT images reconstructed with 60% ASIR under HD mode was greater than that with 0% ASIR (p < 0.05), but lower than that with 80% ASIR. However, under non-HD mode, CAD demonstrated a comparable performance on LDCT images reconstructed with 60% ASIR to those reconstructed with 80% ASIR. CONCLUSION: Using the CAD system to detect pulmonary nodules on LDCT images with appropriate levels of ASIR could maintain high diagnostic sensitivity while reducing the radiation dose, which is useful to optimize the radiology workflow.

Novel imaging phenotypes of naïve asthma patients with distinctive clinical characteristics and T2 inflammation traits.

Objective: This study aims to describe the imaging features of naïve asthma patients, defined as not receiving corticosteroids or other asthma medications for at least 1 month, and their association with therapeutic response, and to discover novel unbiased imaging phenotypes. Methods: A total of 109 naïve asthma patients and 50 healthy controls were enrolled in this study. Clinical data and imaging indices of high-resolution computed tomography were collected. The correlation between imaging indices and clinical features was analyzed. Cluster analyses were adopted to determine three novel imaging phenotypes. Results: Compared with healthy controls, naïve asthma patients presented higher scores of airway remodeling, bronchiectasis, and mucus plugs. Mean airway wall area (WA)% was inversely correlated with mid-expiratory flow velocity% predicted. The extent score of bronchiectasis was positively correlated with smoking history and significantly increased in the high mucus group. Mucus plugs were related to improving lung function and type 2 (T2) inflammation, as assessed by sputum and blood eosinophils and fraction of exhaled nitric oxide. Cluster 1 patients had a high proportion of emphysema, the best lung function, and the lowest T2 inflammation; cluster 2 patients had severe airway remodeling, relatively good lung function, and moderate T2 inflammation; cluster 3 patients had severe airway remodeling, mucus plugs, and bronchiectasis, and showed the worst lung function and highest T2 inflammation. Conclusion: Naïve asthma patients had the imaging traits of airway remodeling, bronchiectasis, and mucus plugs. The unbiased imaging phenotypes had good consistency with clinical characteristics, therapeutic response, and T2 inflammation expression in naïve asthma patients.

CT-Based Radiomics Can Predict the Efficacy of Anlotinib in Advanced Non-Small-Cell Lung Cancer.

Anlotinib is a small-molecule RTK inhibitor that has achieved certain results in further-line treatment, but many patients do not respond to this drug and lack effective methods for identification. Although radiomics has been widely used in lung cancer, very few studies have been conducted in the field of antiangiogenic drugs. This study aims to develop a new model to predict the efficacy of patients receiving anlotinib by combining pretreatment computed tomography (CT) radiomic characters with clinical characters, in order to assist precision medicine of pulmonary cancer. 254 patients from seven institutions were involved in the study. Lesions were selected according to the RECIST 1.1 criteria, and the corresponding radiomic features were obtained. We constructed prediction models based on clinical, NCE-CT, and CE-CT radiomic features, respectively, and evaluated the prediction performance of the models for training sets, internal validation sets, and external validation sets. In the RAD score only model, the area under curve(AUC) of the NCE-CT cohort was 0.740 (95% CI: 0.622, 0.857) for the training set, 0.711 (95% CI: 0.480, 0.942) for the internal validation set, and 0.633(95% CI: 0.479, 0.787) for the external validation set, while that of the CE-CT cohort was 0.815 (95% CI: 0.705, 0.926) for the training set, 0.771 (95% CI: 0.539, 1.000) for the internal validation set, and 0.701 (95% CI: 0.489, 0.913) for the external validation set. In the RAD score-combined model, the AUC of the NCE-CT cohort was 0.796 (95% CI: 0.691, 0.901) for the training set, 0.579 (95% CI: 0.309, 0.848) for the internal validation set, and 0.590 (95% CI: 0.427, 0.753) for the external validation set, while that of the CE-CT cohort was 0.902 (95% CI: 0.828, 0.977) for the training set, 0.865 (95% CI: 0.696, 1.000) for the internal validation set, and 0.837 (95% CI: 0.682, 0.992) for the external validation set. In conclusion, radiomics has accurate predictions for the efficacy of anlotinib. CE-CT-based radiomic models have the best predictive potential in predicting the efficacy of anlotinib, and model predictions become better when they are combined with clinical characteristics.

Reversible Bronchiectasis in COVID-19 Survivors With Acute Respiratory Distress Syndrome: Pseudobronchiectasis.

To retrospectively analyze whether traction bronchiectasis was reversible in coronavirus disease 2019 (COVID-19) survivors with acute respiratory distress syndrome (ARDS), and whether computed tomography (CT) findings were associated with the reversibility, 41 COVID-19 survivors with ARDS were followed-up for more than 4 months. Demographics, clinical data, and all chest CT images were collected. The follow-up CT images were compared with the previous CT scans. There were 28 (68%) patients with traction bronchiectasis (Group I) and 13 (32%) patients without traction bronchiectasis (Group II) on CT images. Traction bronchiectasis disappeared completely in 21 of the 28 (75%) patients (Group IA), but did not completely disappear in seven of the 28 (25%) patients (Group IB). In the second week after onset, the evaluation score on CT images in Group I was significantly higher than that in Group II (p = 0.001). The proportion of reticulation on the last CT images in Group IB was found higher than that in Group IA (p < 0.05). COVID-19 survivors with ARDS might develop traction bronchiectasis, which can be absorbed completely in most patients. Traction bronchiectasis in a few patients did not disappear completely, but bronchiectasis was significantly relieved. The long-term follow-up is necessary to further assess whether traction bronchiectasis represents irreversible fibrosis.

Prospective Study of Low- and Standard-dose Chest CT for Pulmonary Nodule Detection: A Comparison of Image Quality, Size Measurements and Radiation Exposure.

OBJECTIVE: To comprehensively and accurately analyze the out-performance of low-dose chest CT (LDCT) vs. standard-dose CT (SDCT). METHODS: The image quality, size measurements and radiation exposure for LDCT and SDCT protocols were evaluated. A total of 117 patients with extra-thoracic malignancies were prospectively enrolled for non-enhanced CT scanning using LDCT and SDCT protocols. Three experienced radiologists evaluated subjective image quality independently using a 5-point score system. Nodule detection efficiency was compared between LDCT and SDCT based on nodule characteristics (size and volume). Radiation metrics and organ doses were analyzed using Radimetrics. RESULTS: The images acquired with the LDCT protocol yielded comparable quality to those acquired with the SDCT protocol. The sensitivity of LDCT for the detection of pulmonary nodules (n=650) was lower than that of SDCT (n=660). There was no significant difference in the diameter and volume of pulmonary nodules between LDCT and SDCT (for BMI <22 kg/m2, 4.37 vs. 4.46 mm, and 43.66 vs. 46.36 mm3; for BMI ≥22 kg/m2, 4.3 vs. 4.41 mm, and 41.66 vs. 44.86 mm3) (P>0.05). The individualized volume CT dose index (CTDIvol), the size specific dose estimate and effective dose were significantly reduced in the LDCT group compared with the SDCT group (all P<0.0001). This was especially true for dose-sensitive organs such as the lung (for BMI <22 kg/m2, 2.62 vs. 12.54 mSV, and for BMI ≥22 kg/m2, 1.62 vs. 9.79 mSV) and the breast (for BMI <22 kg/m2, 2.52 vs. 10.93 mSV, and for BMI ≥22 kg/m2, 1.53 vs. 9.01 mSV) (P<0.0001). CONCLUSION: These results suggest that with the increases in image noise, LDCT and SDCT exhibited a comparable image quality and sensitivity. The LDCT protocol for chest scans may reduce radiation exposure by about 80% compared to the SDCT protocol.

Assessment of relationships among clinicopathological characteristics, morphological computer tomography features, and tumor cell proliferation in stage I lung adenocarcinoma.

BACKGROUND: Surgically resected stage I lung adenocarcinoma (ADC) has wide variation in prognosis. It is significant to identify high-risk patients and optimize therapeutic strategy. This study aimed to investigate the relationships among histological grade, serum tumor marker index (TMI), morphological computer tomography (CT) features, and a well-established prognosticator cell proliferation (Ki-67) in stage I ADC. METHODS: Preoperative CT was performed in 182 patients with stage I ADC confirmed by pathology. The Ki-67 expression was acquired by immunohistochemistry. TMI was the square root of standardized serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) values. Tumor shadow disappearance rate (TDR) and other morphological CT features were interpreted by two radiologists. Histological grade, TMI, CT features were statistically evaluated to explore the associations with Ki-67 expression. RESULTS: In univariate analysis, gender, smoking history, pack-year, histological grade, TNM stage (IA and IB), serum CEA and CYFRA 21-1 status, TMI status, as well as TDR, long-axis diameter, short-axis diameter, lobulation, spiculation, attenuation types, vacuolation, vascular invasion, vascular convergence, thickened bronchovascular bundles, pleural attachment and peripheral fibrosis were significantly associated with Ki-67 expression (all P<0.05). Solid-predominant ADC had the highest Ki-67 expression, followed by micropapillary, papillary and acinar-predominant ADC, while lepidic-predominant ADC had the lowest Ki-67 expression (P<0.001). TDR was negatively correlated with Ki-67 (r =-0.478, P<0.001). Multivariate logistic regression analysis revealed that gender, histological grade, TDR and attenuation types were independent factors associated with Ki-67 expression. CONCLUSIONS: Ki-67 expression differed distinctly according to ADC histological subtypes. High Ki-67 expression is independently associated with male patients of stage I ADC with worse differentiation, lower TDR and solid tumors, which might be of prognostic value for poor prognosis in stage I ADC.

MR Virtual Endoscopy of the Fetal Limb Anomalies Using Three-Dimensional Fast Imaging Employing Steady-State Acquisition Sequence.

OBJECTIVE: To retrospectively investigate the feasibility of magnetic resonance virtual endoscopy (MRVE) to visualize the normal limbs and limb deformities Methods: MR sequences included two-dimensional (2D) single fast spin-echo sequence and 2D and 3D steady-state procession fast imaging sequences. MRVE reconstruction was retrospectively performed by 2 radiologists in 32 fetuses in 30 pregnant women. The correlation between the radiologists for the virtual endoscopy threshold of MRVE was determined. Image quality and limb segment visibility were independently rated. Area under the receiver operating characteristics curve (AUC) of 2D MRI and MRVE was calculated. RESULTS: The mean virtual endoscopy threshold required for the visualization of the limb was 991.93 ± 12.13 and 991.83 ± 12.26 for 2 radiologists, respectively. The correlation between the radiologists for virtual endoscopy threshold was excellent (r = 0.933). The weighted kappa statistic was 0.96 for the evaluation of image quality of limb segments, indicating excellent interobserver agreement. Compared to that of 2D MRI alone, a higher AUC of 2D MRI with MRVE was achieved in detection of both upper and lower limb deformities (0.91 vs. 0.69 and 0.83 vs. 0.71, respectively). CONCLUSION: MRVE may display normal and abnormal fetal limb orientation and structures from multiple perspectives and provide incremental information for obstetrics.

Early fibroproliferative signs on high-resolution CT are associated with mortality in COVID-19 pneumonia patients with ARDS: a retrospective study.

OBJECTIVES: To investigate the chest high-resolution computed tomography (HRCT) findings in coronavirus disease 2019 (COVID-19) pneumonia patients with acute respiratory distress syndrome (ARDS) and to evaluate its relationship with clinical outcome. MATERIALS AND METHODS: In this retrospective study, 79 COVID-19 patients with ARDS were recruited. Clinical data were extracted from electronic medical records and analyzed. HRCT scans, obtained within 3 days before clinical ARDS onset, were evaluated by three independent observers and graded into six findings according to the extent of fibroproliferation. Multivariable Cox proportional hazard regression analysis was used to assess the independent predictive value of the computed tomography (CT) score and radiological fibroproliferation. Patient survival was determined by Kaplan-Meier analysis. RESULTS: Compared with survivors, non-survivors showed higher rates of lung fibroproliferation, whereas there were no significant differences in the area of increased attenuation without traction bronchiolectasis or bronchiectasis. A HRCT score <230 enabled the prediction of survival with 73.5% sensitivity and 93.3% specificity, 100% negative predictive value (NPP), 83.3% positive predictive value (PPV) and 88.6% accuracy (Area Under the Curve [AUC] = 0.9; 95% confidence Interval [CI] 0.831-0.968). A multivariate Cox proportional hazards model showed that the HRCT score is a significant independent risk factor for mortality (Hazard Ratio [HR] 9.94; 95% CI 4.10-24.12). Kaplan-Meier analysis revealed that a HRCT score ⩾230 was associated with a higher fatality rate. Organ injury occurred less frequently in patients with a HRCT score <230 compared to those with a HRCT score ⩾230. CONCLUSION: Early pulmonary fibroproliferative signs on HRCT are associated with increased mortality and susceptibility to organ injury in COVID-19 pneumonia patients with early ARDS.

Circular RNA circANKRD36 regulates Casz1 by targeting miR-599 to prevent osteoarthritis chondrocyte apoptosis and inflammation.

Osteoarthritis (OA) is an ageing-related disease characterized by articular cartilage degradation and joint inflammation. circRNA has been known to involve in the regulation of multiple inflammatory diseases including OA. However, the mechanism underlying how circRNA regulates OA remains to be elucidated. Here, we report circANKRD36 prevents OA chondrocyte apoptosis and inflammation by targeting miR-599, which specifically degrades Casz1. We performed circRNA sequencing in normal and OA tissues and found the expression of circANKRD36 is decreased in OA tissues. circANKRD36 is also reduced in IL-1ß-treated human chondrocytes. FACS analysis and Western blot showed that the knockdown of circANKRD36 promotes the apoptosis and inflammation of chondrocytes in IL-1ß stress. We then found miR-599 to be the target of circANKRD36 and correlate well with circANKRD36 both in vitro and in vivo. By database analysis and luciferase assay, Casz1 was found to be the direct target of miR-599. Casz1 helps to prevent apoptosis and inflammation of chondrocytes in response to IL-1ß. In conclusion, our results proved circANKRD36 sponge miR-599 to up-regulate the expression of Casz1 and thus prevent apoptosis and inflammation in OA.

Temporal lung changes in high-resolution chest computed tomography for coronavirus disease 2019.

OBJECTIVE: To evaluate temporal lung changes in coronavirus disease 2019 (COVID-19) in high-resolution computed tomography (HRCT) and to determine the appropriate computed tomographic (CT) follow-up time. METHODS: Eighty-six patients with two or more HRCT scans who were diagnosed with COVID-19 were included. The CT score and major CT findings were evaluated. RESULTS: Eighty-two (95.3%) patients had lesions on the initial HRCT scans. Most scans showed bilateral, multifocal lung lesions, with multiple lobes involved and diffuse distribution. For fifty-seven patients with type I (progress compared with the initial CT score), the CT score reached a peak at 12 days and the nadir at 36 days. For twenty-nine patients with type II (no progress compared with the initial CT score), the lowest CT score was reached at 23 days. On the final HRCT scans (>21 days), patients with a reticular pattern were older than those without a reticular pattern. CONCLUSION: The appropriate follow-up time of CT scans is during the second week (approximately 12 days) and the fourth to fifth weeks (approximately 23-36 days) from the onset of illness. These times could help reduce the CT radiation dose and show timely changes in the course of the disease by CT.

Dexamethasone prevents the Epstein-Barr virus induced epithelial-mesenchymal transition in A549 cells.

Clinical data have shown that pulmonary interstitial fibrosis is likely to occur in the later stages of viral pneumonia. While viral infections are thought to cause chronic pulmonary interstitial inflammation and pulmonary fibrosis, it remains unclear if they promote pulmonary fibrosis by epithelial-mesenchymal transition (EMT). In this study, human epithelial cell line A549 has been used to model the infection of the Epstein-Barr virus (EBV) and the respiratory syncytial virus (RSV). Their differences were compared and the possible infection mechanisms analyzed by randomly assigning cells to one of five treatments. Exposure of the LMP1 is thought to be the key gene during EBV-induced EMT in the A549 cells. Enzyme-linked immunosorbent assay analysis revealed that the EBV infection was associated with the induction of a number of cytokines (interleukin-8 [IL-8], IL-13, tumor necrosis factor-α, and transforming growth factor-ß) and dexamethasone (DXM) could significantly prevent the phenotypic changes, and partly the mechanisms related with the IL-13 pathway. Surprisingly, different results were seen with the RSV infection as the A549 cells still displayed an epithelial morphology but the levels of E-cadherin, α-SMA, vimentin, and fibronectin did not change. This is the first study demonstrating the different reactions induced by different viruses, and the protective effects of DXM on the EBV-induced EMT in the A549 cells by partially inhibiting the IL-13 pathway. These findings suggest a novel mechanism, by which DXM or anti-IL-13 may delay the progression of pulmonary fibrosis by preventing the progress of EBV-induced EMT.

Early CT features and temporal lung changes in COVID-19 pneumonia in Wuhan, China.

PURPOSE: To analyse the high-resolution computed tomography (HRCT) early imaging features and the changing trend of coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: Forty-six patients with COVID-19 pneumonia who had an isolated lesion on the first positive CT were enrolled in this study. The following parameters were recorded for each lesion: sites, sizes, location (peripheral or central), attenuation (ground-glass opacity or consolidation), and other abnormalities (supply pulmonary artery dilation, air bronchogram, interstitial thickening, etc.). The follow-up CT images were compared with the previous CT scans, and the development of the lesions was evaluated. RESULTS: The lesions tended to be peripheral and subpleural. All the lesions exhibited ground-glass opacity with or without consolidation. A higher proportion of supply pulmonary artery dilation (89.13 % [41/46]) and air bronchogram (69.57 % [32/46]) were found. Other findings included thickening of the intralobular interstitium and a halo sign of ground glass around a solid nodule. Cavitation, calcification or lymphadelopathy were not observed. The reticular patterns were noted from the 14 days after symptoms onset in 7 of 20 patients (45 %). At 22-31 days, the lesions were completely absorbed only in 2 of 7 patients (28.57 %). CONCLUSION: The typical early CT features of COVID-19 pneumonia are ground-glass opacity, and located peripheral or subpleural location, and with supply pulmonary artery dilation. Reticulation was evident after the 2nd week and persisted in half of patients evaluated in 4 weeks after the onset. Long-term follow-up is required to determine whether the reticulation represents irreversible fibrosis.

Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (2019-nCoV): a study of 63 patients in Wuhan, China.

OBJECTIVES: The purpose of this study was to observe the imaging characteristics of the novel coronavirus pneumonia. METHODS: Sixty-three confirmed patients were enrolled from December 30, 2019 to January 31, 2020. High-resolution CT (HRCT) of the chest was performed. The number of affected lobes, ground glass nodules (GGO), patchy/punctate ground glass opacities, patchy consolidation, fibrous stripes and irregular solid nodules in each patient's chest CT image were recorded. Additionally, we performed imaging follow-up of these patients. RESULTS: CT images of 63 confirmed patients were collected. M/F ratio: 33/30. The mean age was 44.9 ± 15.2 years. The mean number of affected lobes was 3.3 ± 1.8. Nineteen (30.2%) patients had one affected lobe, five (7.9%) patients had two affected lobes, four (6.3%) patients had three affected lobes, seven (11.1%) patients had four affected lobes while 28 (44.4%) patients had 5 affected lobes. Fifty-four (85.7%) patients had patchy/punctate ground glass opacities, 14 (22.2%) patients had GGO, 12 (19.0%) patients had patchy consolidation, 11 (17.5%) patients had fibrous stripes and 8 (12.7%) patients had irregular solid nodules. Fifty-four (85.7%) patients progressed, including single GGO increased, enlarged and consolidated; fibrous stripe enlarged, while solid nodules increased and enlarged. CONCLUSIONS: Imaging changes in novel viral pneumonia are rapid. The manifestations of the novel coronavirus pneumonia are diverse. Imaging changes of typical viral pneumonia and some specific imaging features were observed. Therefore, we need to strengthen the recognition of image changes to help clinicians to diagnose quickly and accurately. KEY POINTS: • High-resolution CT (HRCT) of the chest is critical for early detection, evaluation of disease severity and follow-up of patients with the novel coronavirus pneumonia. • The manifestations of the novel coronavirus pneumonia are diverse and change rapidly. • Radiologists should be aware of the various features of the disease and temporal changes.