[Tumor-associated Macrophage: 
Emerging Targets for Modulating the Tumor Microenvironment].

Tumor-associated macrophage (TAM) play a crucial role in the immune microenvironment of lung cancer. Through changes in their phenotype and phagocytic functions, TAM contribute to the initiation and progression of lung cancer. By promoting the formation of an immune-suppressive microenvironment and accelerating the growth of abnormal tumor vasculature, TAM facilitate the invasion and metastasis of lung cancer. Macrophages can polarize into different subtypes with distinct functions and characteristics in response to various stimuli, categorized as anti-tumor M1 and pro-tumor M2 types. In tumor tissues, TAM typically polarize into the alternatively activated M2 phenotype, exhibiting inhibitory effects on tumor immunity. This article reviews the role of anti-angiogenic drugs in modulating TAM phenotypes, highlighting their potential to reprogram M2-type TAM into an anti-tumor M1 phenotype. Additionally, the functional alterations of TAM play a significant role in anti-angiogenic therapy and immunotherapy strategies. In summary, the regulation of TAM polarization and function opens up new avenues for lung cancer treatment and may serve as a novel target for modulating the immune microenvironment of tumors.
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Polyhexamethylene guanidine accelerates the macrophage foamy formation mediated pulmonary fibrosis.

Polyhexamethylene guanidine (PHMG) is manufactured and applied extensively due to its superior disinfectant capabilities. However, the inhalatory exposure to PHMG aerosols is increasingly recognized as a potential instigator of pulmonary fibrosis, prompting an urgent call for elucidation of the underlying pathophysiological mechanisms. Within this context, alveolar macrophages play a pivotal role in the primary immune defense in the respiratory tract. Dysregulated lipid metabolism within alveolar macrophages leads to the accumulation of foam cells, a process that is intimately linked with the pathogenesis of pulmonary fibrosis. Therefore, this study examines PHMG's effects on alveolar macrophage foaminess and its underlying mechanisms. We conducted a 3-week inhalation exposure followed by a 3-week recovery period in C57BL/6 J mice using a whole-body exposure system equipped with a disinfection aerosol generator (WESDAG). The presence of lipid-laden alveolar macrophages and downregulation of pulmonary tissue lipid transport proteins ABCA1 and ABCG1 were observed in mice. In cell culture models involving lipid-loaded macrophages, we demonstrated that PHMG promotes foam cell formation by inhibiting lipid efflux in mouse alveolar macrophages. Furthermore, PHMG-induced foam cells were found to promote an increase in the release of TGF-ß1, fibronectin deposition, and collagen remodeling. In vivo interventions were subsequently implemented on mice exposed to PHMG aerosols, aiming to restore macrophage lipid efflux function. Remarkably, this intervention demonstrated the potential to retard the progression of pulmonary fibrosis. In conclusion, this study underscores the pivotal role of macrophage foaming in the pathogenesis of PHMG disinfectants-induced pulmonary fibrosis. Moreover, it provides compelling evidence to suggest that the regulation of macrophage efflux function holds promise for mitigating the progression of pulmonary fibrosis, thereby offering novel insights into the mechanisms underlying inhaled PHMG disinfectants-induced pulmonary fibrosis.

Prognostic implications of neutrophil-to-lymphocyte ratio in patients with extensive-stage small cell lung cancer receiving chemoimmunotherapy: A multicenter, real-world study.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are closely related to the prognosis of patients with non-small cell lung cancer, but their effect on extensive-stage small cell lung cancer (ES-SCLC) remains uncertain. METHODS: This retrospective study was conducted in ES-SCLC patients treated with first-line atezolizumab or durvalumab and platinum-etoposide. Clinical data from three hospitals were analyzed. Significant risk factors for survival were identified using descriptive statistics and Cox regression. Homogeneity was assessed using t-tests or nonparametric tests. Kaplan-Meier analysis revealed an association between high NLR level and median PFS and OS. RESULTS: A total of 300 ES-SCLC patients were included in the study. Cox regression analysis revealed that an elevated NLR level after the second treatment cycle (defined as NLRT2) was an independent prognostic factor for survival. Stratifying patients based on median NLRT2 showed significant differences in both PFS (HR: 1.863, 95% CI: 1.62-2.12, p < 0.001) and OS (HR: 2.581, 95% CI: 2.19-3.04, p < 0.001) between NLR ≥ 1.75 and NLR < 1.75 groups. mPFS and mOS were 8.2 versus 6.1 months and 13.7 versus 9.5 months, respectively. NLR was also associated with treatment efficacy and occurrence of irAEs. Further stratification based on NLR and irAEs showed that in the NLR < 1.75 group, patients with irAEs had prolonged mPFS and mOS. In the NLR ≥ 1.75 group, only mPFS showed a significant difference between patients with and without irAEs. CONCLUSION: NLRT2 and irAEs can predict the prognosis of ES-SCLC patients with first-line ES-SCLC receiving PD-L1 inhibitors combined with chemotherapy.

Pulmonary Surfactant Homeostasis Dysfunction Mediates Multiwalled Carbon Nanotubes Induced Lung Fibrosis via Elevating Surface Tension.

Multiwalled carbon nanotubes (MWCNTs) have been widely used in many disciplines and raised great concerns about their negative health impacts, especially environmental and occupational exposure. MWCNTs have been reported to induce fibrotic responses; however, the underlying mechanisms remain largely veiled. Here, we reported that MWCNTs inhalation induced lung fibrosis together with decreased lung compliance, increased elastance in the mice model, and elevated surface tension in vitro. Specifically, MWCNTs increased surface tension by impairing the function of the pulmonary surfactant. Mechanistically, MWCNTs induced lamellar body (LB) dysfunction through autophagy dysfunction, which then leads to surface tension elevated by pulmonary surfactant dysfunction in the context of lung fibrosis. This is a study to investigate the molecular mechanism of MWCNTs-induced lung fibrosis and focus on surface tension. A direct mechanistic link among impaired LBs, surface tension, and fibrosis has been established. This finding elucidates the detailed molecular mechanisms of lung fibrosis induced by MWCNTs. It also highlights that pulmonary surfactants are expected to be potential therapeutic targets for the prevention and treatment of lung fibrosis induced by MWCNTs.

A rare case of pulmonary artery embolism with choriocarcinoma: A case report and literature review.

Pulmonary embolism (PE) caused by malignant tumor is not uncommon, but pulmonary artery with choriocarcinoma is rare and difficult to timely diagnose and effectively treat. To the best of our knowledge, there are only 15 cases reported at present in the literature that present variable clinical characteristics and prognosis. In the current study reports a 21-year-old female with a history of chest pain and slight fever for 4 months who was treated as a case of pneumonia. Owing to the recurrence of the symptoms, a contrast-enhanced chest computer tomography scan was performed on the patient, which revealed complete occlusion of the right pulmonary artery. The patient was diagnosed to have pulmonary embolism (PE). However, no abnormalities were observed in D-dimer value, tumor antigen testing or ultrasonography. Positron emission tomography/computed tomography (PET/CT) was performed, which revealed the abnormal hypermetabolic lesion of the right pulmonary artery. Following the laboratory report of a significantly elevated human chorionic gonadotropin ß-subunit level combined with characteristic appearance of PET-CT, the diagnosis of primary pulmonary artery with choriocarcinoma was established based on guidelines of the European Society for Medical Oncology and the criteria formulated by the International Federation of Gynecology and Obstetrics. The patient underwent chemotherapy and responded well to the treatment. Although rare, choriocarcinoma should be considered for any fertile women who presents with a massive PE. These findings emphasize the importance of the early diagnosis and treatment of this disease.

A predictive role of C-reactive protein in colorectal cancer risk: an updated meta-analysis from 780,985 participants and 11,289 cancer cases.

PURPOSE: This meta-analysis is aimed at understanding the potential role of circulating C-reactive protein (CRP) in the prediction of colorectal cancer (CRC) risk and the potential effect of relevant variables, with specific concern to determine the incorporation of CRP into a CRC risk prediction model. METHODS: Relevant articles on the association between circulating CRP and CRC risk were searched from PubMed, Embase, Web of Science, and Cochrane Database of Systematic Reviews through August 2022. Random-effects models were used to estimate the pooled relative risk (RR) for the highest versus lowest CRP categories. Linear and non-linear trend analyses were conducted to explore the dose-response associations between CRP and CRC risk. RESULTS: Twenty-three articles including 780,985 participants and 11,289 cancer cases met the selection criteria. The overall result demonstrated a remarkable association between elevated CRP levels and CRC risk (RR, 1.259; 95% CI, 1.060-1.457), but not in dose-response analysis (RR, 1.002 (95% CI, 0.964-1.041) per natural log unit change in CRP). Subgroup analyses indicated a significant difference when grouped by study location, the length of follow-up, and gender composition. No evidence of publication bias was observed. CONCLUSION: The predictive role of CRP in CRC incidence is limited to colon cancer and a period of 10 years after the initial discovery of CRP elevation. The result did not support the etiological role of CRP in CRC and the inclusion of CRP into the CRC risk prediction model.

[Research Progress of Immune Checkpoint TIGIT in Lung Cancer Immunotherapy].

T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) is a newly discovered immune checkpoint molecule, mainly expressed on the surface of T cells and natural killer (NK) cells. By binding to cluster of differentiation 155 (CD155) and other ligands, it inhibits T cell and NK cell-mediated immune responses and affects the tumor microenvironment. Multiple preclinical studies have demonstrated that the TIGIT/CD155 pathway plays a role in a variety of solid and hematological tumors. Clinical trials investigating TIGIT inhibitors alone or in combination with programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors for lung cancer are currently underway.
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[Two Cases of TKI-resistant Small Cell Lung Cancer Transformation 
in Advanced Adenocarcinoma and Literature Review].

Treatment of advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can achieve good disease control, but it will inevitably produce drug resistance. About 3%-10% of the resistance mechanism is small cell transformation. Two cases of stage IV lung adenocarcinoma with EGFR mutation were reported and the disease was controlled after EGFR-TKIs treatment. In case 1, progression-free survival (PFS) before small cell carcinoma transformation was 16 months, and in case 2, PFS before small cell carcinoma transformation was 24 months. Subsequent biopsy after disease progression indicated a shift to small cell lung cancer. Case 1 PFS after small cell carcinoma transformation was 6 months, and case 2 PFS after small cell carcinoma transformation was 8 months, and overall survival (OS) was 36 months, which significantly prolonged the patient's survival. At the same time, the literature of such drug resistance mutations was reviewed. For patients with advanced NSCLC with sensitive mutations, it is necessary to conduct secondary histopathological tests after TKIs treatment resistance, and select subsequent treatment according to different resistance mechanisms for the whole course of disease management.
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Chronic carbon black nanoparticles exposure increases lung cancer risk by affecting the cell cycle via circulatory inflammation.

As a widely used pure elemental carbon in colloidal particles, carbon black was listed as a group 2B carcinogen by IARC in 2010. The most available mechanism information about carbon black and carcinogenesis are from in vivo or in vitro studies. However, few studies concerned the nanoparticle's real-ambient exposure causing systemic change and further affecting the target organ. Herein, we used an ex vivo biosensor assay to investigate the transcriptome change of primary bronchial epithelial cells after treatment with the plasma from workers with long-term occupational carbon black exposure history. Based on ex vivo biosensor assay and transcriptome sequencing, we found the effect of internal systemic environment on epithelial cells after carbon black exposure was an inflammatory response, which mainly activates cell cycle-related pathways. After exposure to carbon black, the internal systemic environment could activate cancer-related pathways like epithelial-mesenchymal transition, hypoxia, TNF-α signaling via NF-κB. The hub genes in the carbon black group (CDC20 and PLK1) and their correlation with the systemic environment were uncovered by constructing the protein-protein interaction network. Inflammatory cytokines, especially CRP, were strongly correlated with the expression of CDC20 and PLK1. Besides, we also find a strong correlation between CDC20 and cytokinesis-block micronucleus endpoints in peripheral blood (rho = 0.591, P < 0.001). Our results show that long-term carbon black exposure might activate cell cycle-related pathways through circulating inflammation and increase the risk of cancer, while the oxidative stress caused by diesel exhaust particles are mainly related to PAHs exposure. After exposure to carbon black, the systemic environment could activate cancer-related pathways like diesel exhaust particles, increasing the risk of lung cancer. These attempts might provide a further understanding of the indirect effect of chronic occupational inhaled carbon black exposure on pulmonary carcinogenesis.

Circulatory metabolites trigger ex vivo arterial endothelial cell dysfunction in population chronically exposed to diesel exhaust.

BACKGROUND: Chronic exposure to diesel exhaust has a causal link to cardiovascular diseases in various environmental and occupational settings. Arterial endothelial cell function plays an important role in ensuring proper maintenance of cardiovascular homeostasis and the endothelial cell dysfunction by circulatory inflammation is a hallmark in cardiovascular diseases. Acute exposure to diesel exhaust in controlled exposure studies leads to artery endothelial cells dysfunction in previous study, however the effect of chronic exposure remains unknown. RESULTS: We applied an ex vivo endothelial biosensor assay for serum samples from 133 diesel engine testers (DETs) and 126 non-DETs with the aim of identifying evidence of increased risk for cardiovascular diseases. Environmental monitoring suggested that DETs were exposed to high levels of diesel exhaust aerosol (282.3 µg/m3 PM2.5 and 135.2 µg/m3 elemental carbon). Surprisingly, chronic diesel exhaust exposure was associated with a pro-inflammatory phenotype in the ex vivo endothelial cell model, in a dose-dependent manner with CCL5 and VCAM as most affected genes. This dysfunction was not mediated by reduction in circulatory pro-inflammatory factors but significantly associated with a reduction in circulatory metabolites cGMP and an increase in primary DNA damage in leucocyte in a dose-dependent manner, which also explained a large magnitude of association between diesel exhaust exposure and ex vivo endothelial biosensor response. Exogenous cGMP addition experiment further confirmed the induction of ex vivo biosensor gene expressions in endothelial cells treated with physiologically relevant levels of metabolites cGMP. CONCLUSION: Serum-borne bioactivity caused the arterial endothelial cell dysfunction may attribute to the circulatory metabolites based on the ex vivo biosensor assay. The reduced cGMP and increased polycyclic aromatic hydrocarbons metabolites-induced cyto/geno-toxic play important role in the endothelial cell dysfunction of workers chronic exposure to diesel exhaust.

Niclosamide Ethanolamine Salt Alleviates Idiopathic Pulmonary Fibrosis by Modulating the PI3K-mTORC1 Pathway.

Idiopathic pulmonary fibrosis (IPF) is an interstitial pneumonia characterized by chronic progressive fibrosis, ultimately leading to respiratory failure and early mortality. Although not fully explored, the major causative factors in IPF pathogenesis are dysregulated fibroblast proliferation and excessive accumulation of extracellular matrix (ECM) deposited by myofibroblasts differentiated from pulmonary fibroblasts. More signalling pathways, including the PI3K-Akt-mTOR and autophagy pathways, are involved in IPF pathogenesis. Niclosamide ethanolamine salt (NEN) is a highly effective multitarget small-molecule inhibitor reported in antitumor studies. Here, we reported that in an IPF animal model treated with NEN for 14 days, attractive relief of pulmonary function and hydroxyproline content were observed. To further explore, the therapeutic effect of NEN in IPF and pathological changes in bleomycin-challenged mouse lung sections were assessed. Additionally, the effects of NEN on abnormal proliferation and ECM production in IPF cell models established with TGF-ß1-stimulated A549 cells or DHLF-IPF cells were studied. In nonclinical studies, NEN ameliorated lung function and histopathological changes in bleomycin-challenged mice, and the lung hydroxyproline content was significantly diminished with NEN treatment. In vitro, NEN inhibited PI3K-mTORC1 signalling and arrested the cell cycle to prevent uncontrolled fibroblast proliferation. Additionally, NEN inhibited TGF-ß1-induced epithelial-mesenchymal transition (EMT) and ECM accumulation via the mTORC1-4EBP1 axis. Furthermore, NEN-activated noncanonical autophagy resensitized fibroblasts to apoptosis. The above findings demonstrated the potential antifibrotic effect of NEN mediated via modulation of the PI3K-mTORC1 and autophagy pathways. These data provide strong evidence for a therapeutic role for NEN in IPF.

Human airway organoids as 3D in vitro models for a toxicity assessment of emerging inhaled pollutants: Tire wear particles.

Three-dimensional (3D) structured organoids have become increasingly promising and effective in vitro models, and there is an urgent need for reliable models to assess health effects of inhaled pollutants on the human airway. In our study, we conducted a toxicity assessment of human airway organoids (hAOs) for tire wear particles (TWPs) as an emerging inhaled pollutant. We induced primary human bronchial epithelial cells (HBECs) to generated human airway organoids, which recapitulated the key features of human airway epithelial cells including basal cells, ciliated cells, goblet cells, and club cells. TWPs generated from the wearing of tire treads were considered a major source of emerging inhaled road traffic-derived non-exhaust particles, but their health effect on the lungs is poorly understood. We used human airway organoids to assess the toxicology of tire wear particles on the human airway. In an exposure study, the inhibitory effect of TWPs on the growth of human airway organoids was observed. TWPs induced significant cell apoptosis and oxidative stress in a dose-dependent manner. From the qPCR analysis, TWPs significantly up-regulated the expression pf genes involved in the inflammation response. Additionally, the exposure of TWPs reduced SCGB1A1 gene expression associated with the function of the club cell and KRT5 gene expression related to the function of basal cells. In conclusion, this was first study using human airway organoids for a toxicological assessment of TWPs, and our findings revealed that human airway organoids provide an evaluation model of inhaled pollutants potentially affecting the lungs.

Polyhexamethylene guanidine aerosol triggers pulmonary fibrosis concomitant with elevated surface tension via inhibiting pulmonary surfactant.

Environmental chemicals inhalation exposure could induce pulmonary fibrosis, which is characterized by the excessive proliferation of fibroblasts and accumulation of extracellular matrix components, in which surface tension usually plays vital roles. Polyhexamethylene guanidine (PHMG) was first recognized as a potential hazard ingredient in humidifier disinfectants, which caused an outbreak of pulmonary fibrosis in South Korea. However, the underlying mechanisms involved in PHMG-induced pulmonary fibrosis have not yet been fully elucidated. Therefore, this study mainly focuses on the effect of PHMG on surface tension to unveil the influence and involved mechanisms in PHMG-induced pulmonary fibrosis. C57BL/6J mice were exposed to sub-acute PHMG aerosol for 8 weeks. The results indicated that PHMG induced pulmonary fibrosis combined with elevated surface tension. Results from in vitro study further confirmed PHMG elevated surface tension by inhibited pulmonary surfactant. Mechanistically, PHMG suppressed the key surfactant protein SP-B and SP-C by inhibiting protein expression and block their active sites. The present study, for the first time, revealed the molecular mechanism of PHMG-induced pulmonary fibrosis based on pulmonary surfactant inhibition mediated surface tension elevated. And pulmonary surfactant may be a potential target for further intervention to prevent PHMG-induced fibrosis or alleviate the symptom of relevant patients.

Immune checkpoint inhibitor-induced myocarditis in lung cancer patients: a case report of sintilimab-induced myocarditis and a review of the literature.

Since its initial approval by the United States Food and Drug Administration (FDA) in 2014, the indications for the use of the immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients has increased. However, to date, there has no report on immune myocarditis caused by the ICI sintilimab. In addition, there has been no literature review on ICI-induced myocarditis in lung cancer patients. This is a case report of an elderly male patient who presented with a productive cough and progressive dysphagia for 3 days. The symptoms started on day 6 after the third cycle of sintilimab treatment for his lung carcinoma. In accordance with his clinical manifestations of progressive dysphagia, a previous history of lung cancer, abnormal electrocardiograph, significantly increased serum myocardial enzyme levels, and normal coronary angiography results, sintilimab-induced myocarditis was diagnosed. Methylprednisolone (80-40 mg) was used to inhibit the immune injury and the patient was safely discharged on the 13th day following admission. Since ICI-induced myocarditis is rare and fatal, we summarized the characteristics of 20 cases of the disease in lung cancer patients to highlight to oncologists, respiratory experts, and cardiologists the serious side effects of the drug when they encounter lung cancer patients using ICIs. Like most ICIs, sintilimab induces severe immune myocarditis and requires corticosteroids therapy, and this should be recognized by doctors in multiple departments.

Ambient air pollutants and hospital visits for pneumonia: a case-crossover study in Qingdao, China.

BACKGROUND: Pneumonia is one of the principal reasons for incidence and death in the world. The former research mainly concentrated on specific sources of patients. Besides, due to the heterogeneity among regions, there are inconsistencies in the outcome of these surveys. To explore the relationship between atmospheric pollution and hospital visits for pneumonia under the climate and pollution conditions in Qingdao, we carried out this study. METHODS: The medical records of pneumonia patients were gathered from the affiliated hospital of Qingdao University during Jan 1st, 2014, and Dec 31st,2018. Daily concentrations of PM2.5, PM10, SO2, NO2, as well as CO, were collected from the national air quality monitoring stations in Qingdao. Case-crossover study design and conditional logistic regression model were used to estimate the associations. Daily temperature, relative humidity, and atmospheric pressure were adjusted as the covariates in all models. A principal component analysis was used to solve the multicollinearity between atmospheric pollutants and investigate the relationship between various air pollutants and pneumonia occurs. RESULTS: In the single pollutant model, with interquartile range increment of the density of PM2.5, PM10, NO2 and SO2 at the lag2 days, the odds ratio of hospital visits for pneumonia patients increased by 6.4% (95%CI, 2.3-10.7%), 7.7% (95%CI, 3.2-12.4%), 6.7% (95%CI, 1.0-12.7%), and 7.2% (95%CI, 1.1-13.5%). Stratified analysis showed that pollutants were more significant in the cold period. Besides, the impact of atmospheric particulates on different ages mainly occurs in the young child (0 to 3-year-old). The odds ratio was 1.042 (95%CI, 1.012-1.072) when the principal components of atmospheric pollutants were included in the conditional logistic model. CONCLUSIONS: Our study found a significant relationship between short-term uncovering to PM2.5, PM10, NO2, SO2, and hospital visits for pneumonia in Qingdao. The effect of atmospheric pollutants mainly arose in a cold period. The particulate matter might be the principal reason in inducing hospital visits for pneumonia.

The liver X receptor agonist T0901317 reduces the inflammation of alveolar epithelial cells induced by polyhexamethylene guanidine through inhibition of the NFκB signaling pathway.

BACKGROUND: As a kind of disinfectant, polyhexamethylene guanidine (PHMG) can cause pulmonary inflammation. In addition to liver X receptors (LXRs) playing an important role in cholesterol and lipid metabolism, it has also been found to be involved in inflammation in recent years. This article explores the role of LXRs agonist T0901317 in the inflammation of alveolar epithelial cells induced by PHMG. METHODS: The A549 human alveolar basal epithelial cell line was exposed to PHMG, T0901317, or the nuclear factor (NF)κB inhibitor BAY11-7082. The cell survival rate was used to determine the cytotoxicity of PHMG and T0901317 to A549 cells. Western blot analysis was used to determine the expression of proteins related to the LXRs and the NFκB signaling pathway. Enzyme-linked immunosorbent assay (ELISA) was conducted to examine the expression of inflammatory cytokines such as interleukin (IL)-8 and interleukin (IL)-6. RESULTS: Incubation of A549 cells with PHMG decreased the expression of LXRs-related proteins, reduced the expression of cellular IκB, increased the expression of nuclear NFκB, and increased the levels of the inflammatory cytokineIL-8 and IL-6. However, pretreatment with the LXR agonist T0901317 partially reversed the effects of PHMG. The effects of T0901317on NFκB signaling pathway was similar to that observed with the NFκB inhibitor BAY11-7082. CONCLUSIONS: The LXRs agonist T0901317 may reduce the inflammation of alveolar epithelial cells induced by PHMG by inhibiting the NFκB signaling pathway.

Lung squamous cell carcinoma with rare epidermal growth factor receptor mutation G719X: a case report and literature review.

Asians who develop non-small cell lung cancer (NSCLC) have a chance of approximately 50% of harboring the epidermal growth factor receptor (EGFR) mutation. The G719X mutation in EGFR has 3 subtypes (i.e., G719A, G719C, or G719S), all of them being classified as uncommon EGFR mutations. The EGFR mutation G719X is most often associated with lung adenocarcinoma. Conversely, its occurrence in lung squamous cell carcinoma is rare. Its response to tyrosine kinase inhibitor (TKI) treatment remains unknown. A 50-year-old Asian male with no smoking history was admitted to our hospital (Affiliated Hospital of Qingdao University) with an irritating dry cough and 1 month of progressive dyspnea. The patient was diagnosed with lung squamous cell carcinoma (cT4N3M0, stage IIIC). Lung biopsy revealed the presence of EFGR G719X mutation. The patient received a tracheobronchial stent, targeted therapy, chemotherapy, seed implantation and radiotherapy, and survived for 25.4 months following diagnosis. It is crucial that gene mutation analysis is performed in non-smoking male squamous cell carcinoma patients. Compared to lung adenocarcinoma patients with rare G719X mutation, this lung squamous cell carcinoma patient with G719X-mutant tumor had a higher sensitivity to 2nd-generation EGFR-TKI treatment, but similar progression-free survival. Importantly, the patient clearly benefited from the used comprehensive treatment plan. This article seeks to shed light on the treatment of lung squamous cell carcinoma patients with the uncommon EGFR G719X mutation.

A genetic variation in CHI3L1 is associated with bronchial asthma.

BACKGROUND: This study was aimed to investigate the associations among Chitinase 3-like 1 (CHI3L1) polymorphisms, asthma and plasma YKL-40 levels in Chinese population. MATERIAL AND METHODS: Four CHI3L1 single nucleotide polymorphisms (SNPs) were genotyped. The YKL-40 level in plasma and eosinophil percentage in peripheral blood were quantified. RESULTS: A SNP (rs4950928) in the CHI3L1 promoter was associated with elevated plasma YKL-40 levels (p = .02), asthma (p = .042) and lung function (p = .029 to .002) in this Chinese population. Plasma YKL-40 levels were significantly elevated in patients with asthma compared to those in control subjects (p < .05). Plasma YKL-40 levels were significantly correlated with forced expiratory volume per cent (FEV1%) measurements (p < .05). Although plasma YKL-40 levels were decreased after treatment, the correlation with FEV1% still existed. CONCLUSIONS: CHI3L1 locus is a risk factor for asthma in Chinese population.

TGFß/Smad mediated the polyhexamethyleneguanide areosol-induced irreversible pulmonary fibrosis in subchronic inhalation exposure.

AIM: Polyhexamethylene guanidine (PHMG) is widely used as a disinfectant with broad spectra of bactericidal activity and low oral toxicity. However, inhalation of PHMG can cause pulmonary injury and severe pulmonary fibrosis. The mechanism underlying PHMG aerosol induced pulmonary fibrosis remains unclear. In this study, we aimed to examine the subchronic lung injury and determine potential cytokines involved in PHMG aerosol induced fibrosis. METHODS: C57BL/6N mice were exposed to 1.03 mg/m3 PHMG through aerosol inhalation for 3 weeks, or 3 weeks followed by other 3 weeks recovery. RESULTS: The results indicated that the expression of transforming growth factor-beta1 (TGF-ß1) and extracellular matrix remodeling markers were up-regulated in the PHMG-treated mice and these parameters were aggravated after 3 weeks recovery. Bronchoalveolar lavage fluids (BALFs) analysis showed that the number of total cells was significantly decreased in exposure group. The percentage of macrophages in BALFs decreased significantly whereas the percentage of neutrophils and lymphocytes increased. Extensive collagen deposition was observed in the peribronchiolar and interstitial areas in the PHMG exposed lungs. CONCLUSION: In conclusion, even low-does PHMG aerosol exposure could induce mice pulmonary local inflammation and irreversible fibrosis. In addition, TGF-ß/Smad signaling pathway mediated the extracellular matrix remodeling involved in the development of pulmonary fibrosis.

[Advances in Exosomes in the Pathogenesis and Diagnosis of Lung Cancer].

The incidence of lung cancer is high worldwide, and lung cancer is the leading cause of death from malignant tumors in both men and women. Early diagnosis of lung cancer can significantly improve the patient's prognosis. Therefore, searching for specific markers to assist in the early diagnosis of lung cancer is urgent question. Exosomes are nano-sized microvesicles and contain various biomaterial, including nucleic acids, proteins, and lipids. Exosomes are important carriers of these biomaterial, serve important roles in intracellular communications and signal transduction among tissues. Due to its unique enrichment mechanism, it has the stability and specificity as a biomarker. Exosomes are not only involved in the formation of tumor microenvironment and new blood vessels in lung cancer, but also involved in chemotherapy, targeted therapy response and prognosis assessment. Many research advances bring new hope for prolonging the survival of lung cancer patients. This article reviews the value of exosome specific protein and microRNA (miRNA) in lung cancer in the diagnosis and prognosis of lung cancer.