Non-small cell lung cancer patient with a rare UGP2-ALK fusion protein responded well to alectinib: a case report.

Several rare anaplastic lymphoma kinase (ALK) fusions have been identified in patients with non-small cell lung cancer (NSCLC); however, their treatment is not currently uniform. alectinib has been commonly used to treat rare ALK fusions in patients with NSCLC. This is the first study to report the occurrence of a uridine diphosphate-glucose pyrophosphorylase 2 (UGP2)-ALK fusion in a patient with NSCLC. The patient, who was hospitalized because of shortness of breath lasting 20 days, showed hydrothorax of the left lung under a computerized tomography chest scan. Pathological histology revealed lung adenocarcinoma in the patient. The UGP2-ALK mutation was found by next-generation sequencing. Subsequently, the patient was administered alectinib, and thereafter, the tumor lesion was observed to gradually shrink over the follow-up period. Progression-free survival reached 10 months as of the follow-up date, with no adverse events detected. This case report provides valuable insights into the clinical management of NSCLC patients with UGP2-ALK fusions. Moreover, alectinib is confirmed to be an appropriate therapeutic agent for such patients.

Extracellular vesicles derived from PM2.5-exposed alveolar epithelial cells mediate endothelial adhesion and atherosclerosis in ApoE-/- mice.

Epidemiological studies suggested that PM2.5 (particle matters with an aerodynamic diameter ≤2.5 µm) exposure is associated with atherosclerosis. Extracellular vesicles (EVs) are messengers between intracellular communications which are important in diseases procession. At present, whether EVs derived from PM2.5-exposed alveolar epithelial cells (P-EVs) involve in atherosclerosis has not been clearly understood. This study is performed to investigate the effects of P-EVs on the development of endothelium adhesion and atherosclerosis. Here, ApoE-/- mice were randomized into different groups receiving one of the following treatments, filtered air (FA), PM2.5, PBS, PBS-treated alveolar epithelial cells-derived EVs (EVs), or P-EVs. Then the atherosclerosis level in aortas or aorta sections was evaluated by oil red O staining. The results indicated that ApoE-/- mice treated with P-EVs or PM2.5 showed more obvious atherosclerosis plaques in aortas and aortic arches than those treated with EVs or PBS. Endothelial cells (ECs) were treated with PBS, EVs, P-EVs, or PM2.5. The adhesion property, miRNAs level and expressions of IκBα, phosphorylated IκBα, NF-κB p65, phosphorylated NF-κB p65, and VCAM1 in ECs were determined. It was found that P-EVs activated IκBα-NF-κB-VCAM1 signaling and increased adhesion of ECs, and such effects could be reversed by adalimumab (the TNF-α inhibitor) or miR-326-3p inhibitor. Further study suggested that P-EVs induced upregulation of TNF-α and miR-326-3p in recipient ECs and contributed to the phosphorylation of NF-κB p65. Collectively, EVs derived from PM2.5-exposed alveolar epithelial cells played an important role in the development of atherosclerosis via activating IκBα-NF-κB-VCAM1 signaling.

Automated detection and quantification of COVID-19 pneumonia: CT imaging analysis by a deep learning-based software.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) is an emerging worldwide threat to public health. While chest computed tomography (CT) plays an indispensable role in its diagnosis, the quantification and localization of lesions cannot be accurately assessed manually. We employed deep learning-based software to aid in detection, localization and quantification of COVID-19 pneumonia. METHODS: A total of 2460 RT-PCR tested SARS-CoV-2-positive patients (1250 men and 1210 women; mean age, 57.7 ± 14.0 years (age range, 11-93 years) were retrospectively identified from Huoshenshan Hospital in Wuhan from February 11 to March 16, 2020. Basic clinical characteristics were reviewed. The uAI Intelligent Assistant Analysis System was used to assess the CT scans. RESULTS: CT scans of 2215 patients (90%) showed multiple lesions of which 36 (1%) and 50 patients (2%) had left and right lung infections, respectively (> 50% of each affected lung's volume), while 27 (1%) had total lung infection (> 50% of the total volume of both lungs). Overall, 298 (12%), 778 (32%) and 1300 (53%) patients exhibited pure ground glass opacities (GGOs), GGOs with sub-solid lesions and GGOs with both sub-solid and solid lesions, respectively. Moreover, 2305 (94%) and 71 (3%) patients presented primarily with GGOs and sub-solid lesions, respectively. Elderly patients (≥ 60 years) were more likely to exhibit sub-solid lesions. The generalized linear mixed model showed that the dorsal segment of the right lower lobe was the favoured site of COVID-19 pneumonia. CONCLUSION: Chest CT combined with analysis by the uAI Intelligent Assistant Analysis System can accurately evaluate pneumonia in COVID-19 patients.

Chinese Expert Recommendation for Diagnosis and Treatment of Massive Hemoptysis.

Massive hemoptysis is one of emergency and critical diseases of the respiratory system. The definition of massive hemoptysis has always been different in the literature, which often depends on the quantitative estimation of the amount of hemoptysis, such as the amount of hemoptysis being in the range of 300-600 mL within 24 h, or hemoptysis more than 3 times within 1 week. Each amount of hemoptysis that is greater than 100 mL can be considered as massive hemoptysis, but the amount of hemoptysis is difficult to accurately estimate. Therefore, massive hemoptysis can be defined as any life-threatening hemoptysis and any hemoptysis that may cause airway obstruction and asphyxia. Massive hemoptysis accounts for approximately 5% of all hemoptysis cases and usually indicates the presence of a potentially severe respiratory or systemic disease. The mortality rate of massive hemoptysis is about 6.5-38%. The cause of death is generally shock caused by airway obstruction or excessive bleeding, and asphyxia is the main cause of death. At present, due to insufficient understanding of massive hemoptysis, there are limited technical means in the etiological diagnosis and untimely or improper treatment, resulting in high mortality of massive hemoptysis. Therefore, the diagnosis and treatment of massive hemoptysis needs to be standardized.

Management of Persistent Air Leaks Using Endobronchial Autologous Blood Patch and Spigot Occlusion: A Multicentre Randomized Controlled Trial in China.

BACKGROUND: Optimal management of persistent air leaks (PALs) in patients with secondary spontaneous pneumothorax (SSP) remains controversial. OBJECTIVE: To evaluate the efficacy and safety of endobronchial autologous blood plus thrombin patch (ABP) and bronchial occlusion using silicone spigots (BOS) in patients with SSP accompanied by alveolar-pleural fistula (APF) and PALs. METHODS: This prospective multicentre randomized controlled trial compared chest tube-attached water-seal drainage (CTD), ABP, and BOS that were performed between February 2015 and June 2017 in one of six tertiary care hospitals in China. Patients diagnosed with APF experiencing PALs (despite 7 days of CTD) and inoperable patients were included. Outcome measures included success rate of pneumothorax resolution at the end of the observation period (further 14 days), duration of air leak stop, lung expansion, hospital stay, and complications. RESULTS: In total, 150 subjects were analysed in three groups (CTD, ABP, BOS) of 50 each. At 14 days, 60, 82, and 84% of CTD, ABP, and BOS subjects, respectively, experienced full resolution of pneumothorax (p = 0.008). All duration outcome measures were significantly better in the ABP and BOS groups than in the CTD group (p < 0.016 for all). The incidence of adverse events, including chest pain, cough, and fever, was not significantly different. All subjects in the ABP and BOS groups experienced temporary haemoptysis. Spigot displacement occurred in 8% of BOS subjects. CONCLUSION: ABP and BOS resulted in clinically meaningful outcomes, including higher success rate, duration of air leak stop, lung expansion, and hospital stay, with an acceptable safety profile.

Interventional Bronchoscopy for the Treatment of Malignant Central Airway Stenosis: An Expert Recommendation for China.

Malignant central airway stenosis refers to airway stenosis caused by primary or metastatic malignant tumors which may lead to different levels of dyspnea or asphyxia in patients. With the rapid development of interventional pulmonology, therapeutic bronchoscopy has become one of the main methods for the diagnosis and treatment of malignant central airway stenosis. However, the level of diagnosis and treatment of respiratory intervention techniques in China is uneven at present, the treatment methods are not uniform, the treatment effects vary greatly, and some treatments even lead to serious complications. The interventional treatment technology for malignant central airway stenosis in China needs to be standardized. Therefore, the relevant experts of the Beijing Health Promotion Association Respiratory and Oncology Intervention and Treatment Alliance have formulated this consensus after several rounds of full discussion.

Use of Interferon-γ release assay for the diagnosis of female genital tuberculosis in Northwest China.

BACKGROUND: Female genital tuberculosis (FGTB) is one of the major causes of infertility. However, nonspecific manifestations and the lack of easy access to gold-standard diagnostic test render a diagnostic difficult for FGTB. The objective of this study was to determine T-SPOT.TB (an interferon-γ release assay, IGRA) performance in patients with FGTB. METHODS: A total of 213 female patients with validated T-SPOT.TB results were recruited in this retrospective study. Among which, 103 were confirmed FGTB, and 110 were excluded from tuberculosis (control). Of the confirmed FGTB patients, 52 were confirmed by microbiologically/histopathologically examination, while the remaining 51 were clinically confirmed (successfully responsive to anti-tuberculosis treatment). T-SPOT.TB test was performed in both FGTB and control group during the diagnostic procedure. RESULTS: The overall sensitivity and specificity of T-SPOT.TB were 86.41% and 75.45% respectively. Sensitivity of T-SPOT.TB was significantly higher when compared with conventional tuberculosis diagnostic tests. Moreover, T-SPOT.TB test using pelvic effusion (PE) showed higher sensitivity than using corresponding peripheral blood (PB) (94.44% vs 72.22%, P < 0.001). Mean value of spot forming cells (SFCs) of T-SPOT.TB using PE was significantly higher than that of PB in FGTB group (193 (IQR 105-280) SFCs/2.5 × 105 PEMCs vs 71 (IQR 36-107) SFCs/2.5 × 105 PBMCs, P = 0.01), while this was not detected in control group (11 (IQR 0-22) SFCs/2.5 × 105 PEMCs vs 9 (IQR 0-18) SFCs/2.5 × 105 PBMCs, P = 0.77). CONCLUSION: These results demonstrated that T-SPOT.TB, especially PE T-SPOT.TB, is an useful adjunct in FGTB diagnosis.

Losartan, a selective antagonist of AT1 receptor, attenuates seawater inhalation induced lung injury via modulating JAK2/STATs and apoptosis in rat.

Losartan is a selective antagonist of AngⅠ type (AT1) receptor of Angiotensin Ⅱ (Ang Ⅱ), which is widely used as a clinical medicine for the hypertension. Recent studies have shown that losartan was shown to protect from acute lung injury (ALI). However, the underlying mechanism remains unclear. The aim of this research was to clarify whether Ang Ⅱ participated in the inflammatory response of ALI induced by seawater inhalation, and whether losartan had the protective effects on ALI by blocking the combination of Ang Ⅱ and AT1 receptor. In the current study, the severity of lung injury and the inflammatory reactions during seawater drowning induced ALI were assessed. Besides, we also detected the activation of relative pathways such as NF-κB, JAK2/STATs and apoptosis. The results showed that seawater inhalation could up-regulate the expression of Ang Ⅱ and AT1. While pretreatment of losartan (especially 15 mg/kg and 30 mg/kg) alleviated lung injury by inhibiting Ang-Ⅱ and AT1 receptor combination and in turn decreased the expression of p-NF-κB and activation of JAK2/STATs pathway. We also confirmed that losartan could reduce the apoptotic ratio of cells in the lung by modulating the phosphorylation of JNK and leak of cytochrome C to cytosol. Taken together, these findings demonstrate that losartan might have a therapeutic potential as an anti-inflammatory agent for treating SWI-ALI.

Hypertonicity contributes to seawater aspiration-induced lung injury: Role of hypoxia-inducible factor 1α.

Drowning is an important public health problem, but the mechanism of acute lung injury induced by near-drowning is rarely reported. The aim of this study is to investigate the role of hypertonicity and HIF-1α in seawater aspiration-induced lung injury. Diverse solutions were used to study the effect of hypertonicity on hypoxia, inflammation, vascular leakage, edema, and HIF-1α expression in lungs of rats. The relationship between hypertonicity and hypoxia, when they induced HIF-1α, was studied and the roles of ATM, PI3K, and p38 in the course of hypertonicity inducing HIF-1α were investigated. At last, our conclusion was verified with HIF-1α inhibitor and inducer in seawater aspiration rats. The results showed that hypertonicity, but not isotonicity and hypotonicity, promoted hypoxia, inflammation, vascular leakage, edema, and HIF-1α expression in lungs. Hypertonicity not only induced HIF-1α in a time- and dose-dependent manner but also could increase HIF-1α synergistically with hypoxia in AEC. Furthermore, hypertonicity increased HIF-1α by promoting its mRNA expression through both ATM and PI3K activation and by suppressing its protein degradation through p38 activation. During hyperosmotic stress, the increased HIF-1α promoted the production of the inflammatory cytokines in NR8383 and elevated monolayer permeability through increasing VEGF in RLMVEC. In conclusion, hypertonicity induced by aspirated seawater aggravated lung injury through increasing HIF-1α which promoted inflammation and edema in lung tissues in rats.

3,5,4'-Tri-O-acetylresveratrol Attenuates Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome via MAPK/SIRT1 Pathway.

The aim of the present research was to investigate the protecting effects of 3,5,4'-tri-O-acetylresveratrol (AC-Rsv) on LPS-induced acute respiratory distress syndrome (ARDS). Lung injuries have been evaluated by histological examination, wet-to-dry weight ratios, and cell count and protein content in bronchoalveolar lavage fluid. Inflammation was assessed by MPO activities and cytokine secretion in lungs and cells. The results showed that AC-Rsv significantly reduced the mortality of mice stimulated with LPS. Pretreatment of AC-Rsv attenuated LPS-induced histological changes, alleviated pulmonary edema, reduced blood vascular leakage, and inhibited the MPO activities in lungs. What was more, AC-Rsv and Rsv treatment reduced the secretion of TNF-α, IL-6, and IL-1ß in lungs and NR8383 cells, respectively. Further exploration revealed that AC-Rsv and Rsv treatment relieved LPS-induced inhibition on SIRT1 expression and restrained the activation effects of LPS on MAPKs and NF-κB activation both in vitro and in vivo. More importantly, in vivo results have also demonstrated that the protecting effects of Rsv on LPS-induced inflammation would be neutralized when SIRT1 was in-hibited by EX527. Taken together, these results indicated that AC-Rsv protected lung tissue against LPS-induced ARDS by attenuating inflammation via p38 MAPK/SIRT1 pathway.

4-hydroxyphenylacetic acid attenuated inflammation and edema via suppressing HIF-1α in seawater aspiration-induced lung injury in rats.

4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary inflammation and edema were assessed by enzyme-linked immunosorbent assay (ELISA), bronchoalveolar lavage fluid (BALF) white cell count, Evans blue dye analysis, wet to dry weight ratios, and histology study. Hypoxia-inducible factor-1α (HIF-1α) siRNA and permeability assay were used to study the effect of 4-HPA on the production of inflammatory cytokines and monolayer permeability in vitro. The results showed that 4-HPA reduced seawater instillation-induced mortality in rats. In lung tissues, 4-HPA attenuated hypoxia, inflammation, vascular leak, and edema, and decreased HIF-1α protein level. In primary rat alveolar epithelial cells (AEC), 4-HPA decreased hypertonicity- and hypoxia-induced HIF-1α protein levels through inhibiting the activations of protein translational regulators and via promoting HIF-1α protein degradation. In addition, 4-HPA lowered inflammatory cytokines levels through suppressing hypertonicity- and hypoxia-induced HIF-1α in NR8383 macrophages. Moreover, 4-HPA decreased monolayer permeability through suppressing hypertonicity and hypoxia-induced HIF-1α, which was mediated by inhibiting vascular endothelial growth factor (VEGF) in rat lung microvascular endothelial cell line (RLMVEC). In conclusion, 4-HPA attenuated inflammation and edema through suppressing hypertonic and hypoxic induction of HIF-1α in seawater aspiration-induced lung injury in rats.

An exosomes-related lncRNA prognostic model correlates with the immune microenvironment and therapy response in lung adenocarcinoma.

Recent research highlights the significance of exosomes and long noncoding RNAs (lncRNAs) in cancer progression and drug resistance, but their role in lung adenocarcinoma (LUAD) is not fully understood. We analyzed 121 exosome-related (ER) mRNAs from the ExoBCD database, along with mRNA and lncRNA expression profiles of TCGA-LUAD using "DESeq2", "survival," "ConsensusClusterPlus," "GSVA," "estimate," "glmnet," "clusterProfiler," "rms," and "pRRophetic" R packages. This comprehensive approach included univariate cox regression, unsupervised consensus clustering, GSEA, functional enrichment analysis, and prognostic model construction. Our study identified 134 differentially expressed ER-lncRNAs, with 19 linked to LUAD prognosis. These ER-lncRNAs delineated two patient subtypes, one with poorer outcomes. Additionally, 286 differentially expressed genes were related to these ER-lncRNAs, 261 of which also correlated with LUAD prognosis. We constructed an ER-lncRNA-related prognostic model and calculated an ER-lncRNA-related risk score (ERS), revealing that a higher ERS correlates with poor overall survival in both the Meta cohort and two validation cohorts. The ERS potentially serves as an independent prognostic factor, and the prognostic model demonstrates superior predictive power. Notably, significant differences in the immune landscape were observed between the high- and low-ERS groups. Drug sensitivity analysis indicated varying responses to common chemotherapy drugs based on ERS stratification, with the high-ERS group showing greater sensitivity, except to rapamycin and erlotinib. Experimental validation confirmed that thymidine kinase 1 enhances lung cancer invasion, metastasis, and cell cycle progression. Our study pioneers an ER-lncRNA-related prognostic model for LUAD, proposing that ERS-based risk stratification could inform personalized treatment strategies to improve patient outcomes.

3,5,4'-tri-O-acetylresveratrol ameliorates seawater exposure-induced lung injury by upregulating connexin 43 expression in lung.

The aim of the present study was to examine the effects of 3,5,4'-tri-O-acetylresveratrol on connexin 43 (Cx43) in acute lung injury (ALI) in rats induced by tracheal instillation of artificial seawater. Different doses (50, 150, and 450 mg/kg) of 3,5,4'-tri-O-acetylresveratrol were administered orally for 7 days before modeling. Four hours after seawater inhalation, histological changes, contents of TNF- α , IL-1 ß and IL-10, and the expression of Cx43 in lungs were detected. Besides, the gap junction communication in A549 cells and human umbilical vein endothelial cells (HUVECs) challenged by seawater was also evaluated. Histological changes, increased contents of inflammatory factors, upregulation in gene level, and deregulation in protein level of Cx43 in lungs stimulated by seawater were observed. On the other hand, pretreatment with 3,5,4'-tri-O-acetylresveratrol significantly inhibited infiltration of inflammation, development of pulmonary edema, and contents of inflammatory mediators in lungs. Above all, 3,5,4'-tri-O-acetylresveratrol upregulated the expression of Cx43 in both gene and protein levels, and its intermediate metabolite, resveratrol, also enhanced the gap junction communication in the two cell lines. The results of the present study suggested that administration of 3,5,4'-tri-O-acetylresveratrol may be beneficial for treatment of inflammatorycellsin lung.

Plasma exosomal miR-1290 and miR-29c-3p as diagnostic biomarkers for lung cancer.

Background: Enhancing the diagnostic efficacy of early-stage lung cancer is crucial for improving prognosis. The objective of this study was to ascertain dependable exosomal miRNAs as biomarkers for the diagnosis of lung cancer. Methods: Exosomal miRNA candidates were identified through miRNA sequencing and subsequently validated in various case-control sets using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The correlation between the expression of exosomal miRNAs and the clinicopathological features of lung cancer was investigated. To assess the diagnostic efficacy of exosomal miRNAs for lung cancer, the receiver operating characteristic (ROC) curve analysis was conducted. The optimal cutoff value of exosomal miRNAs was determined in the testing cohort and subsequently confirmed in the validation cohort. Results: The results showed that the expression of exosomal miR-1290 was significantly elevated, while that of miR-29c-3p was significantly decreased in the plasma of lung cancer patients, especially in those with early-stage lung cancer, compared to individuals with benign lung conditions (P < 0.01). Exosomal miR-1290 and miR-29c-3p demonstrated superior diagnostic efficacy compared to conventional tumor biomarkers in distinguishing between lung cancer and benign lung diseases, as evidenced by their respective area under the curve (AUC) values of 0.934 and 0.868. Furthermore, exosomal miR-1290 and miR-29c-3p exhibited higher diagnostic efficiency in early-stage lung cancer than traditional tumor markers, with AUC values of 0.947 and 0.895, respectively. Notably, both exosomal miR-1290 and miR-29c-3p displayed substantial discriminatory capacity in distinguishing between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), as indicated by their respective AUC values of 0.810 and 0.842. Conclusions: The findings of this study provided evidence that exosomal miR-1290 and miR-29c-3p hold significant potential as biomarkers for the early detection of lung cancer, as well as for differentiating between NSCLC and SCLC.

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.

Derivation and Validation of a Predictive Scoring Model of Infections Due to Acinetobacter baumannii in Patients with Hospital Acquired Pneumonia by Gram-Negative Bacilli.

Background: The prognosis of ABA-HAP patients is very poor. This study aimed to develop a scoring model to predict ABA-HAP in patients with GNB-HAP. Methods: A single center retrospective cohort study was performed among patients with HAP caused by GNB in our hospital during January 2019 to June 2019 (the derivation cohort, DC). The variables were assessed on the day when qualified respiratory specimens were obtained. A prediction score was formulated by using independent risk factors obtained from logistic regression analysis. It was prospectively validated with a subsequent cohort of GNB-HAP patients admitted to our hospital during July 2019 to Dec 2019 (the validation cohort, VC). Results: The final logistic regression model of DC included the following variables: transferred from other hospitals (3 points); blood purification (3 points); risk for aspiration (4 points); immunocompromised (3 points); pulmonary interstitial fibrosis (3 points); pleural effusion (1 points); heart failure (3 points); encephalitis (5 points); increased monocyte count (2 points); and increased neutrophils count (2 points). The AUROC of the scoring model was 0.845 (95% CI, 0.796 ~ 0.895) in DC and 0.807 (95% CI, 0.759 ~ 0.856) in VC. The scoring model clearly differentiated the low-risk patients (the score < 8 points), moderate-risk patients (8 ≤ the score < 12 points) and high-risk patients (the score ≥ 12 points), both in DC (P < 0.001) and in VC (P < 0.001). Conclusion: This simple scoring model could predict ABA-HAP with high predictive value and help clinicians to choose appropriate empirical antibiotic therapy.

Photodynamic therapy for primary tracheobronchial malignancy in Northwestern China.

BACKGROUND: Photodynamic therapy (PDT) has been routinely performed to treat tracheobronchial malignancy. However, the experience in tracheobronchial adenoid cystic carcinoma (ACC) and peripheral lung cancer is still insufficient. This study aimed to share the experience of PDT for patients with primary tracheobronchial malignancy, especially the adenoid cystic carcinoma and peripheral lung cancer, and evaluated the efficacy and safety of PDT in Northwestern Chinese patients. METHODS: This study retrospectively analyzed the clinical data of 23 patients with primary tracheobronchial malignancy receiving PDT in our center. The short-term effect was evaluated by the objective tumor response and the clinical response. The long-term effect was estimated by recurrence-free survival (RFS). RESULTS: Of 23 patients, SR was achieved in 18 patients and MR in 3 patients. The clinical symptoms and the quality of life were significantly improved after PDT (P<0.05). And the mean RFS was 8.9 ± 1.9 months. SR for 6 cases of ACC were achieved with significant improvement of clinical symptoms and quality of life. No procedure-related complications appeared. And PDT was successfully performed for the peripheral lung cancer with the guidance of electromagnetic navigation bronchoscopy (ENB). CONCLUSIONS: This study demonstrated that PDT achieved satisfactory efficacy and safety for Northwestern Chinese patients with primary tracheobronchial malignancy. Patients with ACC can benefit from PDT. And ENB-guided PDT is a novel and available option for the peripheral lung cancer. In short, this study accumulated valuable experience for the application of PDT in Chinese patients with primary tracheobronchial malignancy.

17ß-Estradiol administration attenuates seawater aspiration-induced acute lung injury in rats.

There is very little evidence on the value of administering estrogen in cases of seawater drowning which can induce acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Therefore, this study aimed to investigate whether 17ß-estradiol (E2) treatment can attenuate seawater aspiration-induced ALI in rats. In the experiment, ALI was induced by endotracheal instillation of seawater (4mL/kg) and the rats were then given intraperitoneal injection of E2 (5mg/kg) 20min after seawater instillation. Finally, the changes of arterial blood gases which contained hydrogen ion concentration (pH), arterial oxygen tension (PaO(2)) and arterial carbon dioxide tension (PaCO(2)) were measured and the measurement of extravascular lung water (EVLW) was observed. The pulmonary histological changes were evaluated by hematoxylin-eosin stain. The expression of aquaporins (AQPs) 1, AQP5, and estrogen receptor-ß (ERß) was measured by western blotting and immunohistochemical methods. The results showed that compared with normal saline water, seawater aspiration induced more serious ALI in rats which was markedly alleviated by E2 treatment. Meanwhile, the ERß in lung tissues was activated after E2 administration. The seawater aspiration group also presented with severe pulmonary edema which was paralleled with over expressed AQP1 and AQP5. However, the up-regulation of AQP1 and AQP5 was suppressed by the administration of E2, resulting in an attenuation of lung edema. In conclusion, E2 treatment could effectively attenuate seawater aspiration-induced acute lung injury in rats by the down-regulation of AQP1 and AQP5.

Sodium tanshinone iia sulfonate attenuates seawater aspiration-induced acute pulmonary edema by up-regulating Na(+),K(+)-ATPase activity.

Relieving pulmonary edema is the key of a successful treatment to seawater drowning. Sodium tanshinone IIA sulfonate (STS) has been observed to reduce lung edema from lipopolysaccharide (LPS)-induced lung injury. In this study the authors investigated whether STS attenuates seawater aspiration-induced acute pulmonary edema, and examined the effects of sodium-potassium adensosine triphosphatase (Na(+),K(+)-ATPase) on it. Seawater was instilled through an endotracheal tube. The anesthetized and spontaneously breathing rats received STS intraperitoneally after seawater aspiration. Pao(2), lung wet-to-dry weight ratio, and pulmonary microvascular permeability were tested. The authors explored the effects of STS on the expression and activity of Na(+),K(+)-ATPase in vivo and in vitro. Additionally, the authors investigated the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway in the stimulation of Na(+),K(+)-ATPase by STS. The results showed that STS significantly improved hypoxemia, attenuated lung edema, and alleviated seawater-induced lung injury in vivo. Both in vivo and in vitro, it was observed that STS up-regulated the expression and activity of Na(+),K(+)-ATPase. ERK1/2 inhibitor partially blocked the effects of STS on Na(+),K(+)-ATPase activity in alveolar type II cells following seawater incubation. These results indicated that STS could improve seawater aspiration-induced acute pulmonary edema by up-regulating Na(+),K(+)-ATPase activity, and the ERK1/2 signaling pathway may be involved in it.

Tanshinone IIA attenuates seawater aspiration-induced lung injury by inhibiting macrophage migration inhibitory factor.

Inflammation takes responsibility for the seawater aspiration-induced lung injury. Tanshinone IIA (TIIA) can protect lipopolysaccharide-induced lung injury in mice through the inhibition of inflammation, but it is not reported whether TIIA have a protective effect on lung injury induced by seawater aspiration. Macrophage migration inhibitory factor (MIF) plays an important role in acute lung injury. In this study, we observed the effect of TIIA on the seawater aspiration-induced lung injury and the role of MIF in it. Seawater was aspirated into trachea of rats to make the lung injury model. TIIA was administered to investigate its beneficial effect on seawater-induced acute lung injury. The results showed that seawater aspiration led to hyoxemia, pulmonary edema, neutrophil infiltration, and lung histopathologic changes, with the elevated MIF expression in the lung tissues and plasma. However, these changes were attenuated by TIIA. In macrophage cells we also demonstrated that TIIA could inhibit MIF expression, nuclear factor κB (NF-κB) activity and release of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) induced by seawater. Besides, pretreatment with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid (ISO-1), the MIF antagonist, elevated NF-κB and cytokines induced by seawater were also reduced markedly. Furthermore, rMIF treatment alone increased the phosphorylation level of NF-κB and release of cytokines, which was almost abolished by TIIA. Taken together, our results suggested that TIIA exert a protective effect on the seawater aspiration-induced lung injury partly through downregulation of MIF and the subsequent NF-κB activity, as well as expression of IL-6 and TNF-α.