The change of eosinophils in the perioperative period is significantly associated with the prognosis in patients with lung cancer.

Background: This research focuses on the relationship between the changes in peripheral blood eosinophils (PBEs) perioperatively and the prognosis of lung cancer. Methods: The study included 414 lung cancer patients. These patients were divided into the DOWN (186 patients) and UP (209 patients) groups according to perioperative changes in PBEs. Furthermore, overall survival was compared based on pathological stage, pathological type, tumor location, age and sex. Furthermore, the authors analyzed the prediction of PBEs on the prognosis of chemotherapy. Results: The results showed that lung cancer patients in the DOWN group had a better prognosis (p = 0.0121; 95% CI: 0.6915 [0.5184-0.9224]), and the DOWN group patients with normal postoperative PBEs had a better prognosis (p = 0.0115; 95% CI: 0.6721 [0.4938-0.9148]). Conclusion: Lung cancer patients whose postoperative PBEs were lower than preoperative PBEs had a better prognosis.

MicroRNA-762 Modulates Lipopolysaccharide-induced Acute Lung Injury via SIRT7.

BACKGROUND: Inflammation and oxidative stress contribute to the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury (ALI). MicroRNA-762 (miR-762) has been implicated in the progression of inflammation and oxidative stress; however, its role in ALI remains unclear. In this study, we aim to investigate the role and underlying mechanisms of miR-762 in LPS-induced ALI. METHODS: Mice were intravenously injected with miR-762 antagomir, agomir or the negative controls for 3 consecutive days and then received a single intratracheal instillation of LPS (5 mg/kg) for 12 h to establish ALI model. Adenoviral vectors were used to knock down the endogenous SIRT7 expression. RESULTS: An increased miR-762 expression was detected in LPS-treated lungs. miR-762 antagomir significantly reduced inflammation, oxidative stress and ALI in mice, while the mice with miR-762 agomir treatment exhibited a deleterious phenotype. Besides, we found that SIRT7 upregulation was essential for the pulmonoprotective effects of miR-762 antagomir, and that SIRT7 silence completely abolished the anti-inflammatory and anti-oxidant capacities of miR-762 antagomir. CONCLUSION: miR-762 is implicated in the pathogenesis of LPS-induced ALI via modulating inflammation and oxidative stress, which depends on its regulation of SIRT7 expression. It might be a valuable therapeutic target for the treatment of ALI.

Optimum immunotherapy method according to PD-L1 expression in advanced lung cancer: a network meta-analysis.

Aim: To compare the survival of advanced lung cancer patients treated with immune checkpoint inhibitors in different PD-L1 expression. Methods: We performed a network meta-analysis based on 25 trials involving 12,224 patients with different PD-L1 expression levels. Results: The results showed platinum-based chemotherapy plus pembrolizumab or nivolumab and ipilimumab was associated with the best survival rates for patients with <1% PD-L1 expression, while only platinum-based chemotherapy plus pembrolizumab produced better survival than chemotherapy in patients with 1-49% PD-L1 expression. As for patients with ≥50% PD-L1 expression, platinum-based chemotherapy plus pembrolizumab/atezolizumab and pembrolizumab/cemiplimab monotherapy were associated with better survival than chemotherapy. Conclusion: These results provide reference for selecting the optimum immunotherapy method based on the expression of PD-L1 in patients with advanced lung cancer.

Plain language summary Lung cancer has a high incidence and mortality rate, and there are many treatment strategies, including surgery, chemotherapy, targeted therapy and immunotherapy. The emergence of immunotherapy has effectively improved the treatment effect of lung cancer, but different immunotherapy strategies and drugs have inconsistent efficacy in different patients. In this study the expression of PD-L1 was used to differentiate patients, and the survival difference of patients receiving different immunotherapy strategies was explored through statistical methods. This study may help clinicians choose the best immunotherapy methods and drugs for different patients. Systematic review registration: PROSPERO CRD42020186947.

The function and mechanism of microRNA-92a-3p in lipopolysaccharide-induced acute lung injury.

OBJECTIVES: Sepsis-associated acute lung injury (ALI) is a clinically severe respiratory disorder and remains the leading cause of multiple organ failure and mortality. Herein, we used lipopolysaccharide (LPS) to generate sepsis-induced ALI and try to explore the role and mechanism of microRNA-92a-3p (miR-92a-3p) in this process. METHODS: Mice were intravenously injected with miR-92a-3p agomir, antagomir and negative controls for 3 consecutive days and then were intratracheally instillated by LPS (5 mg/kg) for 12 h. To knock down the endogenous A-kinase anchoring protein 1 (AKAP1), mice were intratracheally injected with recombinant adenovirus carrying the short hairpin RNA targeting AKAP1 (shAkap1) at 1 week before LPS administration. RESULTS: miR-92a-3p level was significantly upregulated in the lungs by LPS injection. miR-92a-3p antagomir reduced LPS-induced intrapulmonary inflammation and oxidative stress, thereby preventing pulmonary injury and dysfunction. In contrast, miR-92a-3p agomir aggravated LPS-induced intrapulmonary inflammation, oxidative stress, pulmonary injury and dysfunction. Moreover, we reported that AKAP1 upregulation was required for the beneficial effects of miR-92a-3p antagomir, and that AKAP1 knockdown completely abolished the anti-inflammatory and antioxidant capacities of miR-92a-3p antagomir. CONCLUSION: Our data identify that miR-92a-3p modulates LPS-induced intrapulmonary inflammation, oxidative stress and ALI via AKAP1 in mice.

Combined detection of estrogen and tumor markers is an important reference factor in the diagnosis and prognosis of lung cancer.

The correlation between lung cancer tumor markers and sex differences in lung cancer remains a clinical problem that is worthy of further study. This study investigated the significance of the combined detection of 17ß-estrogen (E2) and tumor markers in the diagnosis and prognosis of lung cancer. A total of 174 patients, including 117 patients with non-small-cell lung cancer (NSCLC) and 57 patients with benign pulmonary lesions (BPL), were enrolled. An enzyme-linked immunosorbent assay was used to detect the expression of E2, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) in patients with NSCLC and BPL to analyze the correlation between E2 and CEA, NSE or CYFRA21-1 expression, and its correlation with clinicopathological features and prognosis. The expression of tumor markers was then examined in different lung cancer cells (A549, H1795, H460, and SK-MES-1). The expression of tumor markers was detected by a real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. The expressions of p-p44/42 mitogen-activated protein kinase (MAPK) and phospho-AKT (p-AKT) were detected by Western blot analysis. The expression levels of E2, CEA, NSE, and CYFRA21-1 in patients with NSCLC were significantly higher than those in patients with BPL ( P < .05); E2 was positively correlated with tumor markers ( P < .01). Patients with a high expression of E2 and tumor markers showed a poor prognosis ( P < .05). RT-quantitative PCR and Western blot analysis showed that the expression levels of CEA, NSE, CYFRA21-1, p-p44/42 MAPK, and p-AKT in the E2 group were higher than those in the other groups ( P < .05). These studies indicate that the interaction of E2 and tumor markers can significantly improve the role of tumor markers in the diagnosis and prognosis of lung cancer.

Interaction of estrogen receptor ß5 and interleukin 6 receptor in the progression of non-small cell lung cancer.

Numerous studies have shown that the estrogen receptor beta (ERß) and interleukin 6 receptor (IL-6R) had interaction in many tumors, including lung cancer. Previous studies found that ERß5 exhibits a different biological function compared with the other subtypes of ERß. Therefore, this study mainly explores the interaction between ERß5 and IL-6R in the progression of lung cancer. We found that the expression of ERß5, IL-6 and glycoprotein 130 (GP130) were significantly increased (P < 0.001) and the 5-year survival rate with the co-expression of ERß5 and GP130 is significantly lower (P = 0.0315) in non-small cell lung cancer (NSCLC) patients. The cell proliferation, invasion, and cell cycle were markedly increased, and the cell apoptotic was markedly inhibited with the concurrent action of ERß5 and IL-6 in A549 cells (P < 0.05). In addition, the expression of ERß5, GP130, p-AKT, and p-44/42 MAPK was also significantly increased in A549 cells (P < 0.05). These results indicate that ERß5 and GP130 can synergistically promote the progression of NSCLC and maybe combined as an independent prognostic factor in patients. In addition, these results also provide a theoretical basis for the combined targeting therapy of ERß5 and GP130 in NSCLC.

[Research progress on interleukin-6 in lung cancer].

As the core of cellular immunotherapy, T cells are important aspects of research and treatment of lung cancer. IL-6 is a costimulatory signal factor of T cells that is directly targeted by lung cancer stem cells. As a highly expressed cytokine in lung cancer cells, IL-6 plays an important role in variety of biological activities such as tumor occurrence, development, invasion and metastasis. This article reviews the research progress on IL-6 in lung cancer, including cancer development and progression, and the therapeutic sensitivity of lung cancer.

High Dose of Estrogen Protects the Lungs from Ischemia-Reperfusion Injury by Downregulating the Angiotensin II Signaling Pathway.

We explored the sex difference in lung ischemia-reperfusion injury (LIRI) and the role and mechanism of estrogen (E2) and angiotensin II (Ang II) in LIRI. We established a model of LIRI in mice. E2, Ang II, E2 inhibitor (fulvestrant), and angiotensin II receptor blocker (losartan) were grouped for treatment. The lung wet/dry weight ratio, natural killer (NK) cells (by flow cytometry), neutrophils (by flow cytometry), expression of key proteins (by Western blot, immunohistochemistry, ELISA, and immunofluorescence), and expression of related protein mRNA (by qPCR) were detected. The ultrastructure of the alveolar epithelial cells was observed by transmission electron microscopy. We found that E2 and Ang II played an important role in the progression of LIRI. The two signaling pathways showed obvious antagonism, and E2 regulates LIRI in the different sexes by downregulating Ang II, leading to a better prognosis. E2 and losartan reduced the inflammatory cell infiltration in lung tissue and key inflammatory factors in serum while fulvestrant and Ang II had the opposite effect. The protective effect of E2 was related with AKT, p38, COX2, and HIF-1α.

An angiotensin system inhibitor (losartan) potentiates antitumor efficacy of cisplatin in a murine model of non-small cell lung cancer.

Objective: Previous studies have demonstrated synergistic antitumor effects of angiotensin system inhibition (ASI) combined with cisplatin therapy in pancreatic cancer. This study examines whether or not synergistic antitumor effects occur with combination ASI and cisplatin treatment in lung cancer, and whether or not ASI-induced changes in epithelial-mesenchymal transition play a role in the mechanism of this antitumor phenomenon. Methods: A set of lung cancer cell lines representing a spectrum of epithelial to mesenchymal phenotypes were identified and characterized. Response of epithelial-mesenchymal transition markers to losartan was characterized. Cell culture models of lung cancer were next treated with losartan, cisplatin, or combination of both. Markers of epithelial-mesenchymal transition or surrogates of other signaling pathways (AKT, Stat3, and programmed death-ligand), and cell viability were quantified. Findings were confirmed in both allogenic and syngeneic in vivo murine flank tumor models. Results: Losartan treatment significantly increased E-cadherin and reduced vimentin in human lung cancer cell lines. Combination treatment with losartan and cisplatin enhanced epithelial markers, reduced mesenchymal markers, inhibited promesenchymal signaling mediators, and reduced cell viability. Findings were confirmed in vivo in a murine flank tumor model with transition from mesenchymal to epithelial phenotype and reduced tumor size following combination losartan and cisplatin treatment. Conclusions: Combination losartan and cisplatin treatment attenuates the epithelial-mesenchymal transition pathway and enhances the cytotoxic effect of chemotherapy with in vitro and in vivo models of non-small cell lung cancer. This study suggests an important role for ASI therapy in the treatment of lung cancer.

Estrogen and insulin-like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice.

Estrogen receptor (ER) and insulin-like growth factor-1 receptor (IGF-1R) signaling are implicated in lung cancer progression. Based on their previous findings, the authors sought to investigate whether estrogen and IGF-1 act synergistically to promote lung adenocarcinoma (LADE) development in mice. LADE was induced with urethane in ovariectomized Kunming mice. Tumor-bearing mice were divided into seven groups: 17ß-estradiol (E2), E2+fulvestrant (Ful; estrogen inhibitor), IGF-1, IGF-1+AG1024 (IGF-1 inhibitor), E2+IGF-1, E2+IGF-1+Ful+AG1024 and control groups. After 14 weeks, the mice were sacrificed, and then the tumor growth was determined. The expression of ERα/ERß, IGF-1, IGF-1R and Ki67 was examined using tissue-microarray-immunohistochemistry, and IGF-1, p-ERß, p-IGF-1R, p-MAPK and p-AKT levels were determined based on Western blot analysis. Fluorescence-quantitative polymerase chain reaction was used to detect the mRNA expression of ERß, ERß2 and IGF-1R. Tumors were found in 93.88% (46/49) of urethane-treated mice, and pathologically proven LADE was noted in 75.51% (37/49). In the E2+IGF-1 group, tumor growth was significantly higher than in the E2 group (p < 0.05), the IGF-1 group (p < 0.05) and control group (p < 0.05). Similarly, the expression of ERß, p-ERß, ERß2, IGF-1, IGF-1R, p-IGF-1R, p-MAPK, p-AKT and Ki67 at the protein and/or mRNA levels was markedly higher in the ligand group than in the ligand + inhibitor groups (all p < 0.05). This study demonstrated for the first time that estrogen and IGF-1 act to synergistically promote the development of LADE in mice, and this may be related to the activation of the MAPK and AKT signaling pathways in which ERß1, ERß2 and IGF-1R play important roles.

Association of preoperative serum IGF- I concentration with clinicopathological parameters in patients with non-small cell lung cancer.

Insulin-like growth factor-I (IGF-I) is a mitogenic and anti-apoptotic factor. Serum IGF-I concentration is related to some cancer risk and tumor progression. The aim of this research was to study the association of preoperative serum IGF-I concentration with clinicopathological parameters and prognosis of non-small cell lung cancer (NSCLC). Preoperative serum IGF-I concentration was measured in 80 consecutive patients with NSCLC who underwent radical lung cancer resection, and 45 patients with benign pulmonary lesion (BPL) by using enzyme linked immunosorbent assay (ELISA). The results showed that the serum IGF-I concentration was elevated and correlated with clinicopathological parameters and overall survival (OS) in NSCLC patients. Serum IGF-I concentration was significantly higher in patients with NSCLC than in those with BPL. The IGF-I concentrations were significantly higher in NSCLC patients with ≥T2, N1-3, and in IIIA-IV but not in those with

Mechanism of CAV and CAVIN Family Genes in Acute Lung Injury based on DeepGENE.

BACKGROUND: The fatality rate of acute lung injury (ALI) is as high as 40% to 60%. Although various factors, such as sepsis, trauma, pneumonia, burns, blood transfusion, cardiopulmonary bypass, and pancreatitis, can induce ALI, patients with these risk factors will eventually develop ALI. The rate of developing ALI is not high, and the outcomes of ALI patients vary, indicating that it is related to genetic differences between individuals. In a previous study, we found multiple functions of cavin-2 in lung function. In addition, many other studies have revealed that CAV1 is a critical regulator of lung injury. Due to the strong relationship between cavin-2 and CAV1, we suspect that cavin-2 is also associated with ALI. Furthermore, we are curious about the role of the CAV family and cavin family genes in ALI. METHODS: To reveal the mechanism of CAV and CAVIN family genes in ALI, we propose DeepGENE to predict whether CAV and CAVIN family genes are associated with ALI. This method constructs a gene interaction network and extracts gene expression in 84 tissues. We divided these features into two groups and used two network encoders to encode and learn the features. RESULTS: Compared with DNN, GBDT, RF and KNN, the AUC of DeepGENE increased by 7.89%, 16.84%, 20.19% and 32.01%, respectively. The AUPR scores increased by 8.05%, 15.58%, 22.56% and 23.34%. DeepGENE shows that CAVIN-1, CAVIN-2, CAVIN-3 and CAV2 are related to ALI. CONCLUSION: DeepGENE is a reliable method for identifying acute lung injury-related genes. Multiple CAV and CAVIN family genes are associated with acute lung injury-related genes through multiple pathways and gene functions.

A pancancer analysis of the oncogenic role of cyclin B1 (CCNB1) in human tumors.

Aberrant levels of the G2/M cyclin cyclin B1 (gene CCNB1) have been associated with multiple cancers; however, the literature lacks a focused and comprehensive analysis of the regulation of this important regulator of cell proliferation in cancer. Through this work, we performed a pancancer analysis of the levels of CCNB1 and dissected aspects of regulation and how this correlates with cancer prognosis. We comprehensively evaluated the expression and promoter methylation of CCNB1 across 38 cancers based on RNA sequencing data obtained from the Cancer Genome Atlas (TCGA). The correlation of CCNB1 with prognosis and the tumor microenvironment was explored. Using lung adenocarcinoma data, we studied the potential upstream noncoding RNAs involved in the regulation of CCNB1 and validated the protein levels and prognostic value of CCNB1 for this disease site. CCNB1 was highly expressed, and promoter methylation was reduced in most cancers. Gene expression of CCNB1 correlated positively with poor prognosis of tumor patients, and these results were confirmed at the protein level using lung adenocarcinoma. CCNB1 expression was associated with the infiltration of T helper cells, and this further correlated with poor prognosis for certain cancers, including renal clear cell carcinoma and lung adenocarcinoma. Subsequently, we identified a specific upstream noncoding RNA contributing to CCNB1 overexpression in lung adenocarcinoma through correlation analysis, expression analysis and survival analysis. This study provides a comprehensive analysis of the expression and methylation status of CCNB1 across several forms of cancer and provides further insight into the mechanistic pathways regulating Cyclin B1 in the tumorigenesis process.

Recurrent chylothorax treated with thoracic duct-venous anastomosis: A retrospective review of medical records.

Objectives: Clinically, recurrent chylothorax is challenging to solve, especially when chylothorax is still present after the thoracic duct is ligated. In this study we explored alternative surgical options to treat complex cases of recurrent chylothorax. Methods: Clinical records, laboratory results, and magnetic resonance imaging scans were retrospectively reviewed for 3 patients with recurrent chylothorax who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from August 8, 2016, to October 30, 2019. Evidence from the surgical treatment of thoracic duct-venous anastomosis was assessed using pictures from the operation room, with follow-up until now. Results: Thoracic duct ligation had failed twice in patient 1, and the other 2 patients each had thoracic duct ligation that failed once again. After undergoing thoracic duct ligation, all 3 patients showed a significant reduction in chest fluid, but their condition soon returned to the same as that before ligation. All 3 patients finally underwent thoracic duct-venous anastomosis. The changes in lymphocyte and granulocyte numbers in the blood system of the patients before and after the operation were not substantial, and the operations had little effect on liver and kidney function. The patients achieved satisfactory treatment results, with follow-up until the present (23-60 months). Conclusions: This research shows that thoracic duct-venous anastomosis is a safe and effective alternative surgical approach for complex recurrent chylothorax.

The mechanism and biomarker function of Cavin-2 in lung ischemia-reperfusion injury.

BACKGROUND: Lung Ischemia Reperfusion injury(LIRI) is one of the most predominant complications of ischemic lung disease. Cavin-2 emerged as a regulator of a variety of cellular processes, including endocytosis, lipid homeostasis, signal transduction and tumorigenesis, but the function of Cavin-2 in LIRI is unknown. The purpose of this study was to determine the predictive potential of Cavin-2 in protecting lung ischemia-reperfusion injury and its corresponding mechanisms. METHODS: We found the strong relationship between Cavin-2 and multiple immune-related genes by deep learning method. To reveal the mechanism of Cavin-2 in LIRI, the LIRI SD rat model was constructed to detect the expression of Cavin-2 in the lung tissue of SD rats after LIRI, and the expression of Cavin-2 in lung cell lines was also detected. The expression of IL-6, IL-10 and MDA in cells after Cavin-2 over-expression or knockdown was examined under hypoxic conditions. The expression levels of p-AKT, p-STAT3 and p-ERK1/2 were measured in over-expressing Cavin-2 cells under hypoxic-ischemia conditions, and then the corresponding blockers of AKT, STAT3 and ERK1/2 were given to verify, whether they play a protective role in LIRI. RESULTS: After hypoxia, the expression of Cavin-2 in rat lung tissues was significantly increased, and the cellular activity and IL-10 in Cavin-2 over-expressing cells were significantly higher than that of the control group, while IL-6 and MDA were significantly lower than that of the control group, while the above results were reversed in Cavin-2 knockdown cells; Meanwhile, the phosphorylation levels of AKT, STAT3, and ERK1/2 were significantly increased in Cavin-2 over-expression cells after hypoxia. When AKT, STAT3, and ERK1/2 specific blockers were given, they lost their protective effect against LIRI. CONCLUSIONS: Cavin-2 shows biomarker potential in protecting lung from ischemia-reperfusion injury through the survivor activating factor enhancement (SAFE) and reperfusion injury salvage kinase (RISK) pathway.

Hypoxia-associated prognostic markers and competing endogenous RNA coexpression networks in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common form of non-small cell lung cancer (NSCLC). Hypoxia has been found in 50-60% of locally advanced solid tumors and is associated with poor prognosis in various tumors, including NSCLC. This study focused on hypoxia-associated molecular hallmarks in LUAD. Fifteen hypoxia-related genes were selected to define the hypoxia status of LUAD by ConsensusClusterPlus based on data from The Cancer Genome Atlas (TCGA). Then, we investigated the immune status under different hypoxia statuses. Subsequently, we constructed prognostic models based on hypoxia-related differentially expressed genes (DEGs), identified hypoxia-related microRNAs, lncRNAs and mRNAs, and built a network based on the competing endogenous RNA (ceRNA) theory. Two clusters (Cluster 1 and Cluster 2) were identified with different hypoxia statuses. Cluster 1 was defined as the hypoxia subgroup, in which all 15 hypoxia-associated genes were upregulated. The infiltration of CD4+ T cells and Tfh cells was lower, while the infiltration of regulatory T (Treg) cells, the expression of PD-1/PD-L1 and TMB scores were higher in Cluster 1, indicating an immunosuppressive status. Based on the DEGs, a risk signature containing 7 genes was established. Furthermore, three differentially expressed microRNAs (hsa-miR-9, hsa-miR-31, hsa-miR-196b) associated with prognosis under different hypoxia clusters and their related mRNAs and lncRNAs were identified, and a ceRNA network was built. This study showed that hypoxia was associated with poor prognosis in LUAD and explored the potential mechanism from the perspective of the gene signature and ceRNA theory.

Development and validation of nomograms based on clinical characteristics and CT reports for the preoperative prediction of precise lymph node dissection in lung cancer.

OBJECTIVE: To develop and validate nomograms for preoperative prediction of precision lymph node (LN) dissection in lung cancer. PATIENTS AND METHODS: The prediction models of each group LNs (LNx) were developed in a primary cohort that consisted of 1380 patients with clinicopathologically confirmed lung cancer. Clinical characteristics and CT reports were extracted. Patients with LNx dissection were divided into training cohort and testing cohort. Nomograms were built through univariate and multivariate regression analysis in the training cohort and internally verified in the testing cohort. The accuracy of the models was verified by constructing survival analysis in patients without LNx dissection. RESULTS: Due to the lack of sufficient patients for LN1, 8, 13, a total of 10 nomograms were constructed in this study, including LN-2 âˆ¼ 7, 9 âˆ¼ 12. According to the nomogram of each group LN, the most common independent risk factors predicting LN status were CT-reported lymphadenectasis, tumor diameter and location, and the others include age, gender, and whether there were multiple nodules, etc. All models showed good discrimination, with the average C-index of 0.738 in the training cohort and 0.707 in the testing cohort. Survival analysis in patients without LNx dissection all showed the high accuracy of each nomogram to predict LN metastasis status and TNM staging. CONCLUSION: We constructed nomograms to predict the metastasis status of each group of lymph nodes based on clinical characteristics and CT reports. Surgeons can accurately determine the extent of lymph node dissection in patients with lung cancer based on our nomogram models before surgery.

Bullectomy used to treat a patient with pulmonary vesicles related to COVID-19: A case report.

BACKGROUND: The corona virus disease 2019 (COVID-19) has been a pandemic for more than one year and estimated to affect the whole world in the near future. CASE SUMMARY: Here we reported that one COVID-19 patient with vesicles was treated by bullectomy. The patient's perioperative laboratory tests were analyzed. The pathological findings of bullectomy were described and compared with those of common bulla cases. CONCLUSION: This patient with vesicles underwent bullectomy and had a poor prognosis. He showed diffuse alveolar damage and extensive necrosis in bullectomy specimen. We hope our report will be of interest for clinicians who will treat COVID-19 patients in the future.

Revealing Cavin-2 Gene Function in Lung Based on Multi-Omics Data Analysis Method.

Research points out that it is particularly important to comprehensively evaluate immune microenvironmental indicators and gene mutation characteristics to select the best treatment plan. Therefore, exploring the relevant genes of pulmonary injury is an important basis for the improvement of survival. In recent years, with the massive production of omics data, a large number of computational methods have been applied in the field of biomedicine. Most of these computational methods are devel-oped for a certain type of diseases or whole diseases. Algorithms that specifically identify genes associated with pulmonary injury have not yet been developed. To fill this gap, we developed a novel method, named AdaRVM, to identify pulmonary injury-related genes in large scale. AdaRVM is the fusion of Adaboost and Relevance Vector Machine (RVM) to achieve fast and high-precision pattern recognition of pulmonary injury genetic mechanism. AdaRVM found that Cavin-2 gene has strong potential to be related to pulmonary injury. As we known, the formation and function of Caveolae are mediated by two family proteins: Caveolin and Cavin. Many studies have explored the role of Caveolin proteins, but people still knew little about Cavin family members. To verify our method and reveal the functions of cavin-2, we integrated six genome-wide association studies (GWAS) data related to lung function traits, four expression Quantitative Trait Loci (eQTL) data, and one methylation Quantitative Trait Loci (mQTL) data by Summary data level Mendelian Randomization (SMR). We found strong relationship between cavin-2 and canonical signaling pathways ERK1/2, AKT, and STAT3 which are all known to be related to lung injury.

MicroRNA-23a-5p Is Involved in the Regulation of Lipopolysaccharide-Induced Acute Lung Injury by Targeting HSP20/ASK1.

Inflammation and oxidative stress contribute to the progression of acute lung injury (ALI). MicroRNA-23a-5p (miR-23a-5p) has been reported to regulate inflammation and oxidative stress; however, its role in ALI is still poorly elucidated. Mice were intravenously treated with the miR-23a-5p antagomir, agomir, or the negative controls for 3 consecutive days and then received a single intratracheal injection of lipopolysaccharide (LPS, 5 mg/kg) to induce ALI. Pulmonary function, bronchoalveolar lavage fluids (BALFs), arterial blood gas, and molecular biomarkers associated with inflammation and oxidative stress were analyzed. In addition, murine peritoneal macrophages were isolated and treated with LPS to verify the role of miR-23a-5p in vitro. We detected an elevation of miR-23a-5p expression in the lungs from ALI mice. The miR-23a-5p antagomir was prevented, whereas the miR-23a-5p agomir aggravated inflammation, oxidative stress, lung tissue injury, and pulmonary dysfunction in LPS-treated mice. Besides, the miR-23a-5p antagomir also reduced the productions of proinflammatory cytokines and free radicals in LPS-treated primary macrophages, which were further augmented in cells following the miR-23a-5p agomir treatment. Additional findings demonstrated that the miR-23a-5p agomir exacerbated LPS-induced ALI via activating apoptosis signal-regulating kinase 1 (ASK1), and that pharmacological or genetic inhibition of ASK1 significantly repressed the deleterious effects of the miR-23a-5p agomir. Moreover, we proved that the miR-23a-5p agomir activated ASK1 via directly reducing heat shock protein 20 (HSP20) expression. miR-23a-5p is involved in the regulation of LPS-induced inflammation, oxidative stress, lung tissue injury, and pulmonary dysfunction by targeting HSP20/ASK1, and it is a valuable therapeutic candidate for the treatment of ALI.