Abstract Study objectives This systematic review and meta-analysis was conducted to evaluate the accuracy of the combined endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) ...and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) techniques and clarify its current role for the mediastinal lymph node staging of lung cancer. Methods Medline, Web of Science, Elsevier and Ovid were searched to identify suitable studies up to 15th July 2012. Two investigators independently reviewed articles and extracted data. All EBUS-TBNA plus EUS-FNA studies for the mediastinal node staging of lung cancer were systematically reviewed. Sensitivity, specificity and other accuracy measures were pooled using random-effect models. Summary receiver operating characteristic curves were used to summarise overall test performance. Results Eight studies met our inclusion criteria. The estimated summary measures for quantitative analysis of EBUS-TBNA plus EUS-FNA for mediastinal nodal staging of lung cancer were sensitivity, 0.86 (95% confidence interval CI, 0.82–0.90); specificity, 1.00 (95% CI, 0.99–1.00); positive likelihood ratio, 51.77 (95% CI, 22.53–118.94); negative likelihood ratio, 0.15 (95% CI, 0.09–0.25); diagnostic odds ratio, 416.83 (95% CI, 140.08–1240.31); and area under the curve (AUC), 0.99. Conclusions The current evidence suggests that the combined technique is more sensitive than EBUS-TBNA or EUS-FNA alone. The diagnostic power of this combined technique is accurate. As an almost completely minimally-invasive examination, EUS-FNA plus EBUS-TBNA may replace more invasive methods for evaluating mediastinal node staging of lung cancer.
Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are common lung disorders characterized by alveolar-capillary barrier disruption and dyspnea, which can ...cause substantial morbidity and mortality. Currently, a cluster of acute respiratory illnesses, known as novel coronavirus (2019-nCoV)-infected pneumonia (NCIP), which allegedly originally occurred in Wuhan, China, has increased rapidly worldwide. The critically ill patients with ARDS have high mortality in subjects with comorbidities. Previously, the excessive recruitment and activation of neutrophils (polymorphonuclear leukocytes PMNs), accompanied by neutrophil extracellular traps (NETs) formation were reported being implicated in the pathogenesis of ALI/ARDS. However, the direct visualization of lung epithelial injuries caused by NETs, and the qualitative and quantitative evaluations of this damage are still lacking. Additionally, those already reported methods are limited for their neglect of the pathological role exerted by NETs and focusing only on the morphological features of NETosis. Therefore, we established a cell-based assay for detecting NETs during lung epithelial cells-neutrophils co-culture using the xCELLigence system, a recognized real-time, dynamic, label-free, sensitive, and high-throughput apparatus. Our results demonstrated that lung epithelial injuries, reflected by declines in cell index (CI) values, could be induced by lipopolysaccharide (LPS)-activated PMNs, or NETs in a time and dose-dependent manner. NETs generation was verified to be the major contributor to the cytotoxicity of activated PMNs; protein components of NETs were the prevailing cytotoxic mediators. Moreover, this cell-based assay identified that PMNs from severe pneumonia patients had a high NETs formative potential. Additionally, acetylsalicylic acid (ASA) and acetaminophen (APAP) were discovered alleviating NETs formation. Thus, this study not only presents a new methodology for detecting the pathophysiologic role of NETs but also lays down a foundation for exploring therapeutic interventions in an effort to cure ALI/ARDS in the clinical setting of severe pneumonia, including the emerging of NCIP.
•A real-time, dynamical and label-free assay for detecting NETs is established using the xCELLigence system.•This establishment relies on the co-culture of lung epithelia and neutrophils, focusing on evaluating NETs’ effects.•This cell-based assay has feasibility and practicality in clinical applications.•This methodology builds a solid foundation for exploring therapies for ALI/ARDS, including the emerging NCIP.
Long non-coding RNAs (lncRNAs) are important epigenetic regulators, which play critical roles in diverse physiological and pathological processes. However, the regulatory mechanism of lncRNAs in lung ...carcinogenesis remains elusive. Here, we characterized a novel oncogenic lncRNA, designated as Lung Cancer Associated Transcript 3 (LCAT3).
We predicted and validated LCAT3 by analyzing RNA-sequencing (RNA-seq) data of lung cancer tissues from TCGA. Methylated RNA immunoprecipitation was performed to assess m6A modification on LCAT3. The LCAT3-FUBP1-MYC axis was assessed by dual-luciferase reporter, RNA immunoprecipitation and Chromatin immunoprecipitation assays. Signaling pathways altered by LCAT3 knockdown were identified using RNA-seq. Furthermore, the mechanism of LCAT3 was investigated using loss-of-function and gain-of-function assays in vivo and in vitro.
LCAT3 was found to be up-regulated in lung adenocarcinomas (LUAD), and its over-expression was associated with the poor prognosis of LUAD patients. LCAT3 upregulation is attributable to N6-methyladenosine (m6A) modification mediated by methyltransferase like 3 (METTL3), leading to LCAT3 stabilization. Biologically, loss-of-function assays revealed that LCAT3 knockdown significantly suppressed lung cancer cell proliferation, migration and invasion in vitro, and inhibited tumor growth and metastasis in vivo. LCAT3 knockdown induced cell cycle arrest at the G1 phase. Mechanistically, LCAT3 recruited Far Upstream Element Binding Protein 1 (FUBP1) to the MYC far-upstream element (FUSE) sequence, thereby activating MYC transcription to promote proliferation, survival, invasion and metastasis of lung cancer cells.
Taken together, we identified and characterized LCAT3 as a novel oncogenic lncRNA in the lung, and validated the LCAT3-FUBP1-MYC axis as a potential therapeutic target for LUAD.
Immune dysregulation in individuals with long COVID has been detected. Differential diagnosis of diffuse infiltration on chest CT in long COVID is challenging.
A 62-year-old man presented with a ...10-month history of dyspnea after COVID-19 infection. Dyspnea became worse in the one month preceding presentation. The chest CT showed multifocal, subpleural, bilateral opacities due to long-COVID, and infiltration around the bronchovascular bundle in the bilateral lower lung field. The pathology for the transbronchial cryobiopsy (TBCB) first reported chronic inflammation (mainly interstitial pneumonia). The patient had positive results on tests for the antibody, RO-52+, EJ+. The presumptive diagnosis of connective tissue disease-interstitial lung disease was made. Prednisone and cyclophosphamide were given. At follow-up one month later, the chest CT showed new diffuse ground-glass infiltration. The previous TBCB specimen was re-evaluated. Foamy macrophages were found in the alveolar air space. Periodic acid-Schiff (PAS) staining was performed. Numerous intracytoplasmic organisms were detected, with morphologic features consistent with those of Tropheryma whipplei. The patient recovered after intravenous ceftriaxone and oral trimethoprim-sulfamethoxazole. The final diagnosis was lung T. whipplei infection and long COVID-19.
This is the first case report of Tropheryma whipplei infection in the lung of a patient with long COVID-19. T. whipplei should be considered as a potential pathogen for diffuse lung infiltration in the post-COVID-19 era.
A prominent cause of cancer-related fatalities with a poor prognosis is lung adenocarcinoma (LUAD). KIF5A, a crucial member of the kinesin superfamily, is linked to drug resistance in malignancies. ...This work aims to investigate the mechanism of KIF5A in docetaxel (DTX) resistance in LUAD cells. The results of bioinformatics analysis, qRT-PCR and western blot analysis show that KIF5A, which is involved in the glycolysis pathway, is highly expressed in LUAD and is positively correlated with glycolysis-related genes. We further verify that silencing of
inhibits DTX resistance, glycolysis, and lactate production in LUAD cells via cell counting kit-8 (CCK-8), flow cytometry, Seahorse XFe 96, lactate, and glucose assays. Mechanistically, KIF5A promotes DTX resistance in LUAD, and this effect is attenuated upon the addition of an LDHA inhibitor. Chromatin immunoprecipitation and dual-luciferase reporter assays reveal that FOXP3 transcriptionally activates KIF5A. Knockdown of
reduces lactate production and enhances DTX sensitivity in LUAD, which is restored upon simultaneous overexpression of KIF5A. Our findings reveal that FOXP3 increases DTX resistance in LUAD cells by enhancing lactate production through the upregulation of KIF5A level. In conclusion, our study provides a novel treatment target for improving chemosensitivity in LUAD.
Pulmonary blastoma (PB) is a very rare malignant lung tumor consisting of classic biphasic PB, well-differentiated fetal adenocarcinoma, and pleuropulmonary blastoma. We herein present an unusual ...case involving a patient with classic biphasic PB who underwent right upper lobe resection and subsequent treatment. No standard treatment guidelines are available for PB because of its rarity. Our patient received nedaplatin plus paclitaxel as adjuvant chemotherapy. After disease recurrence, the patient received two cycles of etoposide-cisplatin and six cycles of pemetrexed, bevacizumab, and carboplatin. Because of severe adverse effects of the chemotherapy, the patient was finally administered anlotinib, a new oral multikinase inhibitor. Both the tumor size and the serum tumor marker concentration decreased. In conclusion, surgical excision is the treatment of choice for PB. Chemotherapy in the present case resulted in PB activity that was consistent with the literature. Targeted therapies including antiangiogenic agents should be considered as a new treatment option for this rare disease.
•Breath Analysis is promising no invasive technique.•VOC profile Help distinguish early stage lung cancer from advanced stage lung cancer.•VOC profile helps distinguish early stage lung cancer from ...benign pulmonary nodules and healthy controls.
Breath analysis is a promising noninvasive technique that offers a wide range of opportunities to facilitate early diagnosis of lung cancer (LC).
Exhaled breath samples of 352 subjects including 160 with lung cancer (LC), 70 with benign pulmonary nodule (BPN) and 122 healthy controls (HC) were analyzed through thermal desorption coupled with gas chromatography-mass spectrometry (TD-GC–MS) to obtain the metabolic information from volatile organic compounds (VOCs). Statistical classification models were used to find diagnostic clusters of VOCs for the discrimination of HC, BPN and LC patients’ early and advanced stages, as well as subtypes of LC. Receiver operator characteristics (ROC) curves with 5-fold validations were used to evaluate the accuracy of these models.
The analysis revealed that 20, 19, 19, and 20 VOCs discriminated LC from HC, LC from BPN, histology and LC stages respectively. The calculated diagnostic indices showed a large area under the curve (AUC) to distinguish HC from LC (AUC: 0.987, 95 % confidence interval (CI): 0.976−0.997), BPN from LC (AUC: 0.809, 95 % CI: 0.758−0.860), NSCLC from SCLC (AUC: 0.939, 95 % CI: 0.875−0.995) and Stage III from stage III-IV (AUC: 0.827, 95 % CI: 0.768−0.886). The comparison between the high-risk groups (BPN and HC smokers) and early stages LC resulted in the AUC of 0.756 (95 %CI: 0.681−0.817) for BPN vs. early stage LC and AUC of 0.986 (95 % CI: 0.972−0.994) for HC smoker vs. early stage LC.
Volatome of breath of the LC patients was significantly different from that of both BPN patients and HC and showed an ability of distinguishing early from advance stage LC and NSCLC from SCLC. We conclude that the volatome has a potential to help improve early diagnosis of LC.
Objective
A retrospective study was carried out to construct a postoperative venous thromboembolism (VTE) risk assessment model (RAM) applicable for Chinese colorectal cancer patients.
Methods
541 ...Patients who underwent colorectal cancer surgery from June 2019 to May 2020 at Sir-Run-Run-Shaw Hospital affiliated to Zhejiang University School of Medicine were enrolled in this study. Multi-factor analysis was used to determine the independent risk factors of VTE. A novel RAM of VTE which we called Sir-Run-Run-Shaw VTE RAM were constructed basing on the independent risk factors. Another study cohort consisted of 287 colorectal cancer patients underwent surgery from January 2021 to June 2021was used for model evaluation.
Results
The incidence of VTE after colorectal cancer surgery was 12.0%(65/541). Among the 65 VTE Patients, DVT accounted for 92.3% (60/65) and DVT + PE accounted for 7.7% (5/65). Multi-factor analysis showed that age ≥ 69 years (P < 0.01), preoperative plasma D-dimer ≥ 0.49 mg/L (P = .004), stage IV of cancer (P = .018) and transfusion (P = .004) are independent risk factors of VTE after surgery. Sir-Run-Run-Shaw VTE RAM includes the above 4 factors, and the total score is 4 points. The score of the low, medium and high risk groups are 0, 1 and ≥2 points. The area under the ROC curve (AUC) of Sir-Run-Run-Shaw VTE RAM is 0.769, while Caprini RAM is 0.656. There is statistical difference between the two risk score tables (Z = 2.337, P = .0195).
Conclusion
A VTE RAM is constructed basing on a single center retrospective study. This score table may be applicable for Chinese patients with colorectal cancer surgery.
The risk of venous thromboembolism in patients with mental illness has been insufficiently addressed. This study aimed to assess the correlation between hyperhomocysteinemia and venous ...thromboembolism prevalence among this population.
Patients with a diagnosis of mental illness and concurrent venous thromboembolism, admitted to Sir Run Run Shaw Hospital at Zhejiang University School of Medicine between January 2014 and December 2021, were included in the venous thromboembolism group. The control group, approximately twice the size, comprised individuals with mental illness but without venous thromboembolism. Basic clinical data were gathered for both cohorts.
In psychiatric patients, elevated D-dimer levels(OR=5.60,95% CI 3.28-10.00), hyperhomocysteinemia (OR=2.37,95% CI 1.10-5.14), and hyperprolactinemia(OR= 2.68,95% CI 1.12-6.42)were significant risk factors for venous thromboembolism. According to further subgroup analyses, hyperhomocysteinemia is a significant risk factor associated with pulmonary embolism, with an OR of 5.08 (95% CI 1.20-21.48). An interaction effect between gender and homocysteine level was found, with a p-interaction of 0.022. A subsequent analysis confirmed the association between hyperhomocysteinemia and venous thromboembolism in female psychiatric patients, with an OR of 3.34 (95% CI 1.68-6.65), indicating that hyperhomocysteinemia is a significant risk factor for venous thromboembolism in women.
Patients with psychiatric disorders were found to have an elevated risk of venous thromboembolism, which was associated with increased levels of D-dimer, hyperprolactinemia, and hyperhomocysteinemia. A strong correlation between hyperhomocysteinemia and pulmonary embolism was identified in patients with mental illnesses. Furthermore, the study revealed that female psychiatric patients with hyperhomocysteinemia constituted a high-risk group for venous thromboembolism. This finding holds significant clinical implications, suggesting that early preventative measures could be implemented for this high-risk population to reduce the incidence of thromboembolic events during hospitalization for psychiatric patients.
Pulmonary arterial hypertension (PAH) is a rare but fatal cardiopulmonary disease mainly characterized by pulmonary vascular remodeling. Aberrant expression of circRNAs has been reported to play a ...crucial role in pulmonary vascular remodeling. The existing literature predominantly centers on studies that examined the sponge mechanism of circRNAs. However, the mechanism of circRNAs in regulating PAH-related protein remains largely unknown. This study aimed to investigate the effect of circItgb5 on pulmonary vascular remodeling and the underlying functional mechanism.
High-throughput circRNAs sequencing was used to detect circItgb5 expression in control and PDGF-BB-treated pulmonary arterial smooth muscle cells (PASMCs). Localization of circItgb5 in PASMCs was determined via the fluorescence in situ hybridization assay. Sanger sequencing was applied to analyze the circularization of Itgb5. The identification of proteins interacting with circItgb5 was achieved through a RNA pull-down assay. To assess the impact of circItgb5 on PASMCs proliferation, an EdU assay was employed. Additionally, the cell cycle of PASMCs was examined using a flow cytometry assay. Western blotting was used to detect biomarkers associated with the phenotypic switch of PASMCs. Furthermore, a monocrotaline (MCT)-induced PAH rat model was established to explore the effect of silencing circItgb5 on pulmonary vascular remodeling.
CircItgb5 was significantly upregulated in PDGF-BB-treated PASMCs and was predominately localized in the cytoplasm of PASMCs. In vivo experiments revealed that the knockdown of circItgb5 attenuated MCT-induced pulmonary vascular remodeling and right ventricular hypertrophy. In vitro experiments revealed that circItgb5 promoted the transition of PASMCs to synthetic phenotype. Mechanistically, circItgb5 sponged miR-96-5p to increase mTOR level and interacted with Uba1 protein to activate the Ube2n/Mdm2/ACE2 pathway.
CircItgb5 promoted the transition of PASMCs to synthetic phenotype by interacting with miR-96-5p and Uba1 protein. Knockdown of circItgb5 mitigated pulmonary arterial pressure, pulmonary vascular remodeling and right ventricular hypertrophy. Overall, circItgb5 has the potential for application as a therapeutic target for PAH.
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