Probe-based confocal laser endomicroscopy for evaluating high-altitude pulmonary edema in canines.

Background: Real-time assessment of high-altitude pulmonary edema (HAPE) remains a challenge. Probe-based confocal laser microscopy (pCLE) allows a real-time in vivo visualization of the alveoli. This study aimed to develop a new non-invasive method for analyzing microscopic images in a canine model of HAPE using pCLE. Materials and methods: This was a prospective, controlled animal study in adult male beagle dogs randomized to control and HAPE groups. The HAPE group was exposed to a high altitude of 6000 m for 48 h. The blood gas levels, lung morphological changes, infectious factors, and lung wet-to-dry ratio were analyzed in different groups. The pCLE images were described based on the volume air index (VAI), which applies an integral over specific signal intensities. Results: The lung wet-to-dry weight ratio and injury scores in the HAPE group were significantly increased compared with those of the control group. The levels of infectious factors interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6 were significantly increased in the HAPE group compared with those in the control group. VAI was significantly decreased in the HAPE group. Conclusion: pCLE is a potential adjudicative bronchoscopic imaging technique for assessing HAPE. VAI may be acquired from quantitative parameters in the analysis of images.

LCMR1 Promotes Large-Cell Lung Cancer Proliferation and Metastasis by Downregulating HLA-Encoding Genes.

Lung cancer is notorious for its high global morbidity and mortality. Here, we examined whether the LCMR1 gene, which we previously cloned from a human large-cell lung carcinoma cell line, contributes to the proliferation and metastasis of large-cell lung carcinoma. To this end, we performed pan-cancer and non-small cell lung cancer (NSCLC) cell line-based LCMR1 expression profiling. Results revealed that LCMR1 was expressed at high levels in most solid tumors, including NSCLC. LCMR1 expression was the highest in the 95D large cell lung cancer cell line. Functional studies using lentivirus-based knockdown revealed that LCMR1 was critical for the proliferation, migration, and invasion of cultured large cell lung cancer cells. Moreover, blocking this gene significantly reduced tumor growth in a 95D cell xenograft mouse model. A multiple sequence-based assay revealed a mechanism by which LCMR1 diminished the RNA Pol II occupancy at the promoter of human leukocyte antigen (HLA)-encoding genes to prevent their transcription. The HLA genes play vital roles in cancer-specific antigen presentation and anticancer immunity. A correlation assay using TCGA database identified a negative relationship between the expression levels of LCMR1 and HLA coding genes. Taken together, our findings demonstrate that LCMR1 is required for large cell lung cancer cell growth and invasion and suggest its potential as a valid target in clinical treatment.

Diagnostic value of endobronchial ultrasound elastography in differentiating between benign and malignant hilar and mediastinal lymph nodes: a retrospective study.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a first-line approach for diagnosing hilar and mediastinal lymph node metastasis. Endobronchial ultrasound (EBUS) elastography is an imaging technique for describing the elasticity of intrathoracic lesions. However, the reported accuracy of EBUS elastography needs to be improved. In this study, we aimed to explore the diagnostic value of EBUS elastography for differentiating between benign and malignant hilar and mediastinal lymph nodes. Methods: We conducted a single-center, retrospective study enrolling consecutive patients who received EBUS elastography followed by EBUS-TBNA at the Chinese PLA General Hospital from October 2015 to October 2022. The pathological results of EBUS-TBNA confirmed by 6-month follow-up were used as the gold standard. The ultrasound elastography parameters of lymph nodes included strain rate, stiff area ratio, and elasticity score, along with the conventional ultrasound characteristics such as short axis diameter, shape, margin, echogenicity distribution and intensity, and blood flow. The diagnostic performance of these parameters was compared, and conjointly analyzed using multivariate logistic regression. Bootstrapping resampling was applied for internal validation of the regression model. Results: A total of 83 patients were enrolled with an average age of 57 years, and 66.3% of patients were male. In total, 131 lymph nodes were punctured, among which 79 (60.3%) were malignant. All the conventional ultrasound characteristics were significantly different between benign and malignant lymph nodes. All the ultrasound elastography parameters of malignant lymph nodes were markedly higher than those of benign lymph nodes. Multivariate logistic regression analysis showed that the margin, echogenicity intensity, blood flow, short axis diameter, and stiff area ratio were the main factors affecting the lymph node property. The diagnostic accuracy, sensitivity, and specificity were 91.8% [95% confidence interval (CI): 85.4-96.0%], 94.4% (95% CI: 86.4-98.5%), and 88.0% (95% CI: 75.7-95.5%), respectively. Bootstrap resampling validation showed a concordance index (C-index) of 0.949. The calibration plot indicated good agreement between the predicted and observed results. Conclusions: EBUS elastography is a promising approach for differentiating between benign and malignant lymph nodes. The combination of conventional EBUS and elastography can improve diagnostic efficacy, provide reliable complementary information, and guide the implementation of EBUS-TBNA more accurately.

Establishing a predictive model for tumor mutation burden status based on CT radiomics and clinical features of non-small cell lung cancer patients.

Background: Tumor mutation burden (TMB) is one of the biomarkers for efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Due to the potential of radiomic signatures to identify microscopic genetic and molecular differences, thus radiomics is considered a suitable tool for judging the TMB status probably. In this paper, the radiomics method was applied to analyze the TMB status of NSCLC patients, so as to construct a prediction model for distinguishing between TMB-high and TMB-low status. Methods: A total of 189 NSCLC patients with TMB detection result were retrospectively included between 30 November 2016 and 1 January 2021, and were divided into two groups: TMB-high (≥10/Mb, 46 patients) and TMB-low (<10/Mb, 143 patients). Some clinical features related to TMB status were screened out in 14 clinical features and 2,446 radiomic features were extracted. All patients were randomly divided into a training set (n=132) and a validation set (n=57). Univariate analysis and least absolute shrinkage and selection operator (LASSO) were used for radiomics feature screening. A clinical model, radiomics model, and nomogram were constructed with the above screened features and compared. Decision curve analysis (DCA) was used to evaluate the clinical value of the established models. Results: Two clinical features (smoking history, pathological type) and 10 radiomics features were significantly correlated with the TMB status. The prediction efficiency of the intra-tumoral model was better than that of the peritumoral model (AUC: 0.819 vs. 0.816; accuracy: 0.773 vs. 0.632, specificity: 0.767 vs. 0.558). The efficacy of the prediction model based on radiomic features was significantly better than that of the clinical model (AUC: 0.822 vs. 0.683; specificity: 0.786 vs. 0.643). The nomogram, established by combining smoking history, pathologic type, and rad-score, showed the best diagnostic efficacy (AUC =0.844) and had potential clinical value in assessing the TMB status of NSCLC. Conclusions: The radiomics model based on CT images of NSCLC patients performed well in distinguishing the status of TMB-high and TMB-low, and the nomogram could provide additional information on the timing and regimen of immunotherapy.

Deletion of LCMR1 in alveolar type II cells induces lethal impairment of lung structure and function in adult mice.

Background: Previous studies of lung cancer metastasis-related protein 1 (LCMR1) mainly focused on its relationship with cancer. However, the function of LCMR1 in normal tissues or cells is poorly understood. We aimed to investigate the effects of alveolar type II cell (AT2 cell)-specific LCMR1 deletion on lung structure and function in adult mice. Methods: Mice carrying the floxed LCMR1 allele with exons 2-4 flanked by loxP sites were constructed and then crossed with Sftpc-CreERT2 mice to obtain Sftpc-CreERT2 ; LCMR1 flox/flox for AT2 cell-specific LCMR1 deletion and LCMR1 flox/flox mice as littermate control. We observed the body weight change, histopathology, lung wet/dry weight ratio, pulmonary function, and survival of the mice, together with the protein concentration, inflammatory cells, and cytokine levels in bronchoalveolar lavage fluid. We also detected AT2 cell numbers and expression of pulmonary surfactant protein in the lung tissues. The apoptosis of AT2 cells was also assessed. Results: We found that AT2 cell-specific LCMR1 deletion caused rapid weight loss and increased mortality in mice. Histopathological analysis revealed damaged lung structure, including inflammatory cell infiltration, alveolar hemorrhage, and edema. The lung wet/dry weight ratio was higher and bronchoalveolar lavage fluid (BALF) analysis revealed elevated protein concentration, inflammatory cell counts, and cytokine levels. Pulmonary function measurement showed increased airway resistance, decreased lung compacity, and compliance. We also found massive AT2 cell loss and altered expression of pulmonary surfactant protein. Deletion of LCMR1 promoted apoptosis in AT2 cells. Conclusions: We successfully generated an AT2 cell-specific LCMR1 conditional knockout mouse model and further revealed the crucial role of LCMR1 in maintaining AT2 cell homeostasis.

Chinese expert consensus on interventional diagnosis and management of acquired digestive-respiratory tract fistulas (second edition).

Acquired digestive-respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large-scale evidence-based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive-respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive-respiratory tract fistulas. The guidelines conduct an in-depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.

Directed Asymmetric Nickel-Catalyzed Reductive 1,2-Diarylation of Electronically Unactivated Alkenes.

Transition-metal catalyzed intermolecular 1,2-diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition-metal catalyzed asymmetric 1,2-diarylation of unactivated alkenes still remains unsolved and is a formidable challenge. Herein, we describe a highly efficient directed nickel-catalyzed reductive 1,2-diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2-diarylation of the unactivated terminal and challenging internal alkenes is achieved, furnishing various polyarylalkanes featuring benzylic stereocenters in high yields and with good to high enantioselectivities and high diastereoselectivities. Interestingly, the generation of cationic Ni-catalyst by adding alkali metal fluoride is the key to increased efficiency of this enantioselective reaction.

Nickel-Catalyzed Enantioselective Coupling of Acid Chlorides with α-Bromobenzoates: An Asymmetric Acyloin Synthesis.

The reaction of common acyl-metal species (acyl anion) with aldehydes to furnish acyloins has received much less attention and specifically was restricted to using preformed stoichiometric acyl-metal reagents. Moreover, the (catalytic) enantioselective variants remain unexplored, and the asymmetric synthesis of chiral acyloins has met significant challenges in organic synthesis. Here, we uncover the highly enantioselective coupling of acid chlorides with α-bromobenzoates by nickel catalysis for producing enantioenriched protected α-hydroxy ketones (acyloins, >60 examples) with high enantioselectivities (up to 99% ee). The successful execution of this enantioselective coupling protocol enables the formation of a key ketyl radical from α-bromoalkyl benzoate in situ generated from corresponding aldehyde and acyl bromide, which finally is captured by chiral acyl-Ni species catalytically in situ formed from acyl chlorides, thus avoiding the use of preformed acyl-metal reagents. The synthetic utility of this chemistry is demonstrated in the downstream synthetic elaboration toward a diverse set of synthetically valuable chiral building blocks and biologically active compounds.

Endobronchial valve therapy for patients with advanced emphysema. A report from a tertiary care center in China.

OBJECTIVES: To assess the efficiency and safety of endobronchial valve (EBV) treatment in Chinese patients. METHODS: A retrospective analysis was performed in patients with chronic obstructive pulmonary disease who underwent EBV implantation in our hospital between October 2010 and January 2017. All patients were confirmed with no collateral ventilation (CV-) or with low airflow (LF) in the treated lobe. Pulmonary function parameters, the 6-minute walk distance (6MWD), the modified Medical Research Council (mMRC), as well as adverse events in the follow-up period were recorded. RESULTS: Thirty-eight advanced emphysema patients received EBV implantation. Significant improvements were found in forced expiratory volume in 1 second (FEV1)(FEV1: +0.12 L), 6MWD (+64.9 m), and mMRC (-0.5 points). A total of 55.3% and 65.8% of subjects met the score for the minimal clinically important difference in FEV1 and 6MWD, respectively. FEV1 improved more significantly in the CV- group than in the LF group. Pneumothorax or death did not occur during the follow-up period. CONCLUSION: Endobronchial valve treatment in patients with advanced emphysema and CV- provides clinically meaningful benefits with a low incidence of pneumothorax. The efficiency and safety of EBV therapy are acceptable in China.

Novel image features of optical coherence tomography for pathological classification of lung cancer: Results from a prospective clinical trial.

Background: This study aimed to explore the characteristics of optical coherence tomography (OCT) imaging for differentiating between benign and malignant lesions and different pathological types of lung cancer in bronchial lesions and to preliminarily evaluate the clinical value of OCT. Methods: Patients who underwent bronchoscopy biopsy and OCT between February 2019 and December 2019 at the Chinese PLA General Hospital were enrolled in this study. White-light bronchoscopy (WLB), auto-fluorescence bronchoscopy (AFB), and OCT were performed at the lesion location. The main characteristics of OCT imaging for the differentiation between benign and malignant lesions and the prediction of the pathological classification of lung cancer in bronchial lesions were identified, and their clinical value was evaluated. Results: A total of 135 patients were included in this study. The accuracy of OCT imaging for differentiating between benign and malignant bronchial lesions was 94.1%, which was significantly higher than that of AFB (67.4%). For the OCT imaging of SCC, adenocarcinoma, and small-cell lung cancer, the accuracies were 95.6, 94.3, and 92%, respectively. The accuracy, sensitivity, and specificity of OCT were higher than those of WLB. In addition, these main OCT image characteristics are independent influencing factors for predicting the corresponding diseases through logistic regression analysis between the main OCT image characteristics in the study and the general clinical features of patients (p<0.05). Conclusion: As a non-biopsy technique, OCT can be used to improve the diagnosis rate of lung cancer and promote the development of non-invasive histological biopsy.

Correlation between PD-L1 expression and radiomic features in early-stage lung adenocarcinomas manifesting as ground-glass nodules.

Background: Immunotherapy might be a promising auxiliary or alternative systemic treatment for early-stage lung adenocarcinomas manifesting as ground-glass nodules (GGNs). This study intended to investigate the PD-L1 expression in these patients, and to explore the non-invasive prediction model of PD-L1 expression based on radiomics. Methods: We retrospectively analyzed the PD-L1 expression of patients with postoperative pathological diagnosis of lung adenocarcinomas and with imaging manifestation of GGNs, and divided patients into positive group and negative group according to whether PD-L1 expression ≥1%. Then, CT-based radiomic features were extracted semi-automatically, and feature dimensions were reduced by univariate analysis and LASSO in the randomly selected training cohort (70%). Finally, we used logistic regression algorithm to establish the radiomic models and the clinical-radiomic combined models for PD-L1 expression prediction, and evaluated the prediction efficiency of the models with the receiver operating characteristic (ROC) curves. Results: A total of 839 "GGN-like lung adenocarcinoma" patients were included, of which 226 (26.9%) showed positive PD-L1 expression. 779 radiomic features were extracted, and 9 of them were found to be highly corelated with PD-L1 expression. The area under the curve (AUC) values of the radiomic models were 0.653 and 0.583 in the training cohort and test cohort respectively. After adding clinically significant and statistically significant clinical features, the efficacy of the combined model was slightly improved, and the AUC values were 0.693 and 0.598 respectively. Conclusions: GGN-like lung adenocarcinoma had a fairly high positive PD-L1 expression rate. Radiomics was a hopeful noninvasive method for predicting PD-L1 expression, with better predictive efficacy in combination with clinical features.

Malignancy risk stratification for solitary pulmonary nodule: A clinical practice guideline.

CLINICAL QUESTION: The detection rate of the solitary pulmonary nodule (SPN) is increasing with the popularization of CT scanning. Malignancy risk stratification for SPN is a major clinical difficulty. CURRENT PRACTICE: There have been several guidelines for SPN assessment. Inconsistency of these guidelines makes the clinical application difficult and confusing. RECOMMENDATIONS: In this Rapid Recommendation, solid and subsolid SPNs are recommended to be evaluated respectively. Six factors, namely the combination of age with sex, smoking history, history of malignancy, family history of malignancy, and nodule size, are recommended for malignancy risk stratification for both kinds of SPNs; the border of nodules (spiculation and lobulation) is recommended for evaluating solid SPNs and the density of nodules (pure or mixed ground-glass nodule) is recommended for subsolid nodules. Among them, smoking history and radiologic features (nodule diameter, border, and density) are of relatively higher importance. A scoring system was proposed to assist malignancy risk stratification of SPNs, with a total score ranging from six points to 15 points (if solid) or 17 points (if subsolid). For each SPN, regardless of solid or subsolid in nature, a total score of ≤ 7 points suggested a low risk of being malignant, while 7 to 9 points suggested medium risk, and ≥ 9 points suggested high risk. HOW THIS GUIDELINE WAS CREATED: This rapid recommendation was developed using the MAGIC (Making GRADE the Irresistible Choice) methodological framework. First, a clinical subcommittee identified the topic of recommendation and requested evidence. Then, an independent evidence synthesis subcommittee performed a comprehensive literature review and evaluated the evidence. Finally, based on findings from the systematic review and use of real-world data, the clinical subcommittee formulated recommendations, including the scoring system, through a consensus procedure. THE EVIDENCE: A total of 13857 patients with SPNs were included in the meta-analysis and the association between 12 candidate factors and the risk of SPNs being malignant was studied. Eventually, seven factors were recommended for SPNs evaluation, and a scoring system was proposed. UNDERSTANDING THE RECOMMENDATION: The parameters included are objective. Therefore, this recommendation is feasible in clinical practice. However, there are several uncertainties, such as a lack of further verification. It might be misclassified by the scoring system. Clinicians could choose the most suitable scheme according to the recommendation, along with their own experience in specific situations.

Efficacy and Safety of Befotertinib (D-0316) in Patients With EGFR T790M-Mutated NSCLC That Had Progressed After Prior EGFR Tyrosine Kinase Inhibitor Therapy: A Phase 2, Multicenter, Single-Arm, Open-Label Study.

INTRODUCTION: Befotertinib (D-0316) is a novel, third-generation EGFR tyrosine kinase inhibitor (TKI). This study evaluated befotertinib in patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy. METHODS: This was a single-arm, open-label, phase 2 study at 49 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC harboring EGFR T790M mutations with disease progression after prior first- or second-generation EGFR TKI therapy received oral befotertinib of 50 mg (cohort A) or 75 to 100 mg (cohort B) once daily. The primary end point was objective response rate (ORR) assessed by an independent review committee in intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT03861156. RESULTS: A total of 176 patients and 290 patients were included in cohorts A (50 mg) and B (75-100 mg), respectively. At data cutoff (August 15, 2021), independent review committee-assessed ORR was 67.6% (95% confidence interval [CI]: 61.9%-72.9%) in cohort B. The investigator-assessed ORR was 54.0% (95% CI: 46.3%-61.5%) in cohort A and 65.9% (95% CI: 60.1%-71.3%) in cohort B. The median investigator-assessed progression-free survival was 11.0 (95% CI: 9.6-12.5) months in cohort A and 12.5 (95% CI: 11.1-13.8) months in cohort B. The median independent review committee-assessed progression-free survival in cohort B was 16.6 (95% CI: 15.0-not evaluable [NE]) months. The intracranial ORR was 26.7% (95% CI: 7.8%-55.1%) in cohort A by investigator assessment, while 57.1% (95% CI: 34.0%-78.2%) and 55.9% (95% CI: 37.9%-72.8%) in cohort B by investigator and independent review committee assessment, respectively. The median investigator-assessed intracranial progression-free survival was 16.5 (95% CI: 8.6-NE) months in cohort A, while the median intracranial progression-free survival was not evaluable in cohort B due to immature data regardless of investigator or independent review committee assessment. and NE (95% CI: 13.8-NE) in cohort B. The overall survival was immature. Grade 3 or higher treatment-related adverse events and treatment-related serious adverse events occurred in 20.5% and 11.4% of patients in cohort A and in 29.3% and 10.0% of patients in cohort B, respectively. CONCLUSIONS: Befotertinib of 75 to 100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second-generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072).

Clinical Analysis of Non-AIDS Patients with Pulmonary Cryptococcosis and the Change in Their Clinical Features over 30 Years in a Tertiary Hospital in Beijing, China.

Over the past few decades, the clinical features of pulmonary cryptococcosis (PC) have progressed; however, there is a lack of data on the manifestations of PC over time. To investigate the differences in the clinical characteristics of PC across different time periods, we retrospectively reviewed 130 non-acquired immunodeficiency syndrome (AIDS) patients diagnosed with pathologically or microbiologically confirmed PC from 1990-2020. Among the 130 patients with PC, 24 (18.5%) exhibited immunosuppression, and 44 (33.8%) had underlying diseases. In radiology, 118 (90.8%) presented with subpleural lesions, and 68 (53.1%) presented with nodules with diameters ranging from 1-5 cm. Seventy-five (57.7%) patients underwent surgery alone. The clinical features of PC at different time periods showed that hospitalization days decreased (P = 0.009), and the number of patients with symptoms decreased over time. The number of patients exhibiting isolated lesions decreased (P = 0.022), and the number of patients exhibiting subpleural lesions increased (P = 0.020). In addition, the number of patients with lesions presenting 3-10 mm nodules increased (P = 0.028). In conclusion, an increasing number of patients have been diagnosed with PC over the last 30 years. The timing of PC diagnosis has shifted to the early stages of disease progression. Pulmonary lesions caused by cryptococcosis are easily misdiagnosed and may require unnecessary surgical treatment. Further research is needed to identify the lung lesions caused by cryptococcosis.

A computerized tomography-based radiomic model for assessing the invasiveness of lung adenocarcinoma manifesting as ground-glass opacity nodules.

BACKGROUND: Clinically differentiating preinvasive lesions (atypical adenomatous hyperplasia, AAH and adenocarcinoma in situ, AIS) from invasive lesions (minimally invasive adenocarcinomas, MIA and invasive adenocarcinoma, IA) manifesting as ground-glass opacity nodules (GGOs) is difficult due to overlap of morphological features. Hence, the current study was performed to explore the diagnostic efficiency of radiomics in assessing the invasiveness of lung adenocarcinoma manifesting as GGOs. METHODS: A total of 1018 GGOs pathologically confirmed as lung adenocarcinoma were enrolled in this retrospective study and were randomly divided into a training set (n = 712) and validation set (n = 306). The nodules were delineated manually and 2446 intra-nodular and peri-nodular radiomic features were extracted. Univariate analysis and least absolute shrinkage and selection operator (LASSO) were used for feature selection. Clinical and semantic computerized tomography (CT) feature model, radiomic model and a combined nomogram were constructed and compared. Decision curve analysis (DCA) was used to evaluate the clinical value of the established nomogram. RESULTS: 16 radiomic features were selected and used for model construction. The radiomic model exhibited significantly better performance (AUC = 0.828) comparing to the clinical-semantic model (AUC = 0.746). Further analysis revealed that peri-nodular radiomic features were useful in differentiating between preinvasive and invasive lung adenocarcinomas appearing as GGOs with an AUC of 0.808. A nomogram based on lobulation sign and radiomic features showed the best performance (AUC = 0.835), and was found to have potential clinical value in assessing nodule invasiveness. CONCLUSIONS: Radiomic model based on both intra-nodular and peri-nodular features showed good performance in differentiating between preinvasive lung adenocarcinoma lesions and invasive ones appearing as GGOs, and a nomogram based on clinical, semantic and radiomic features could provide clinicians with added information in nodule management and preoperative evaluation.

Development of a diagnostic model for malignant solitary pulmonary nodules based on radiomics features.

Background: This study proposed a precise diagnostic model for malignant solitary pulmonary nodules (SPNs). This model can be used to identify objective and quantifiable image features and guide the clinical treatment strategy adopted for SPNs. This model will help clinicians optimize management strategies for SPN. Methods: In this retrospective study, the clinical data of 455 patients of SPN with defined pathological diagnosis between September 2016 and August 2019 were collected and analyzed. The data included pathological diagnosis, preoperative computed tomography (CT) diagnosis, gender, age, smoking history, family history of tumor, previous history, and contact history data. The quantitative image features and radiomic information of the SPNs were provided using computer-aided detection (CAD) "digital lung" software. The Chi-squared test was used to assess the accuracy between CAD and conventional CT in the diagnosis of SPNs. The diagnostic model for benign or malignant SPNs was developed using a multivariate logistic regression analysis that comprises 6 radiomic factors (irregularity, average diameter, COPD910, proportion of emphysema, proportion of fat, and average density of related blood vessels). The area under the receiver operating characteristic curve was used to evaluate the performance of the model in determining SPN risk of malignancy. Results: There was a statistical difference in the accuracy of CAD and conventional CT in diagnosing SPNs. According to the golden standard pathological diagnosis, the diagnostic accuracy of CAD (81%) was higher than that of conventional CT (63.7%) (P<0.05). Six variables (i.e., irregularity, the mean diameter, COPD910, the proportion of emphysema, the proportion of fat, and the vascular density) were identified using multivariable logistic regression to establish the diagnostic model for distinguish benign or malignant SPNs. The area under the receiver operating characteristic (ROC) curve (AUC) of the diagnostic model was 0.876 (95% CI: 0.8445-0.9076), and its sensitivity and specificity were 81.25% and 82.56% respectively. Conclusions: The proposed diagnostic model, which comprises 6 radiomic factors, is accurate and effective at diagnosing benign or malignant SPNs.

Predicting Ki-67 labeling index level in early-stage lung adenocarcinomas manifesting as ground-glass opacity nodules using intra-nodular and peri-nodular radiomic features.

OBJECTIVES: To explore the diagnostic value of radiomics in differentiating between lung adenocarcinomas appearing as ground-glass opacity nodules (GGO) with high- and low Ki-67 expression levels. MATERIALS AND METHODS: From January 2018 to January 2021, patients with pulmonary GGO who received lung resection were evaluated for potential enrollment. The included GGOs were then randomly divided into a training cohort and a validation cohort with a ratio of 7:3. Logistic regression (LR), decision tree (DT), support vector machines (SVM), and adaboost (AB) were applied for radiomic model construction. Area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of the established models. RESULTS: Seven hundred and sixty-nine patients with 769 GGOs were included in this study. Two hundred and forty-five GGOs were confirmed to be of high Ki-67 labeling index (LI). In the training cohort, gender, age, spiculation sign, pleural indentation sign, bubble sign, and maximum 2D diameter of the nodule were found to be significantly different between high- and low Ki-67 LI groups (p < 0.05), and spiculation sign and maximum 2D diameter of the nodule were further confirmed to be risk factors for Ki-67 LI. The radiomic model established using SVM exhibited an AUC of 0.731 in the validation cohort, which was higher than that of the clinical-radiographic model (AUC = 0.675). Moreover, radiomic model combining both intra- and peri-nodular features showed better diagnostic efficacy than using intra-nodular features alone (AUC = 0.731 and 0.720, respectively). CONCLUSIONS: The established radiomic model exhibited good diagnostic efficacy in differentiating between lung adenocarcinoma GGOs with high and low Ki-67 LI, which was higher than the clinical-radiographic model. Peri-nodular radiomic features showed added benefits to the radiomic model. As a novel noninvasive method, radiomics have the potential to be applied in the preliminary classification of Ki-67 expression level in lung adenocarcinoma GGOs.

Current status of diagnosis and treatment of advanced non-small cell lung cancer in China during the COVID-19 pandemic.

BACKGROUND: The purpose of this study was to investigate the current status of diagnosis and treatment of Chinese patients with advanced non-small cell lung cancer (NSCLC) and the expert recommendation of the therapeutic regimens during the coronavirus disease 2019 (COVID-19) pandemic, and to analyze and summarize relevant rules. METHODS: Under the planning and coordination of the Lung Cancer Group of the Chinese Thoracic Society, we performed an online questionnaire survey among experts in lung cancer and patients with NSCLC. Convenience sampling was adopted for questionnaire survey of experts, and random sampling was adopted for questionnaire survey of patients. After collecting and sorting out the questionnaire, a descriptive analysis of the data was performed. RESULTS: Within 24 h from the distribution of questionnaires to the deadline, a total of 808 and 321 valid questionnaires from patients and experts were collected across China, respectively. There were 83.81% of the experts performed moderately and strongly anti-tumor therapy for patients with NSCLC during the COVID-19 pandemic. 76.6% of patients mainly receive online public welfare treatment, and the patient satisfaction rate reached up to 64.97%. For driver gene-positive patients with advanced NSCLC and non-COVID-19, 82.87% of the experts recommended first-line simple targeted therapy, and 12.77% of the experts recommended targeted therapy with oral anti-angiogenic drugs. For patients who were unable to return to the hospital for treatment and showed resistance to the tyrosine kinase inhibitor (TKI) therapy, 92.21% of the experts recommended oral anti-angiogenic drugs as the third-line home-based therapy and above. For patients with advanced NSCLC combined with COVID-19, 98.76% and 95.95% of the experts recommended discontinuation of chemotherapy and immunotherapy, respectively. CONCLUSIONS: During COVID-19, most Chinese patients with NSCLC were still able to receive timely diagnosis and treatment either by online public welfare consultation or at nearby hospitals.

Human mesenchymal stromal cells small extracellular vesicles attenuate sepsis-induced acute lung injury in a mouse model: the role of oxidative stress and the mitogen-activated protein kinase/nuclear factor kappa B pathway.

BACKGROUND AIMS: Acute lung injury (ALI) secondary to sepsis is a complex disease associated with high morbidity and mortality. Mesenchymal stem cells (MSCs) and their conditioned medium have been demonstrated to reduce alveolar inflammation, improve lung endothelial barrier permeability and modulate oxidative stress in vivo and in vitro. Recently, MSCs have been found to release small extracellular vesicles (sEVs) that can deliver functionally active biomolecules into recipient cells. The authors' study was designed to determine whether sEVs released by MSCs would be effective in sepsis-induced ALI mice and to identify the potential mechanisms. METHODS: A total of 6 h after cercal ligation and puncture, the mice received saline, sEV-depleted conditioned medium (sEVD-CM) or MSC sEVs via the tail vein. RESULTS: The administration of MSC sEVs improved pulmonary microvascular permeability and inhibited both histopathological changes and the infiltration of polymorphonuclear neutrophils into lung tissues. In addition, the activities of antioxidant enzymes were significantly increased in the group treated with sEVs compared with the saline and sEVD-CM groups, whereas lipid peroxidation was significantly decreased. Furthermore, sEVs were found to possibly inhibit phosphorylation of the mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-κB) pathway and degradation of IκB but increase the activities of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1. CONCLUSIONS: These findings suggest that one of the effective therapeutic mechanisms of sEVs against sepsis-induced ALI may be associated with upregulation of anti-oxidative enzymes and inhibition of MAPK/NF-κB activation.

[Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer].

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS: Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.