Objectives: To evaluate the incidence and mortality of acute respiratory distress syndrome (ARDS) in medical/ respiratory intensive care units (MICUs/RICUs) to assess ventilation management and the use of adjunct therapy in routine clinical practice for patients fulfilling the Berlin definition of ARDS in mainland China. Methods: This was a multicentre prospective longitudinal study. Patients who met the Berlin definition of ARDS were included. Baseline data and data on ventilator management and the use of adjunct therapy were collected. Results: Of the 18,793 patients admitted to participating ICUs during the study timeframe, 672 patients fulfilled the Berlin ARDS criteria and 527 patients were included in the analysis. The most common predisposing factor for ARDS in 402 (77.0) patients was pneumonia. The prevalence rates were 9.7% (51/527) for mild ARDS, 47.4% (250/527) for moderate ARDS, and 42.9% (226/527) for severe ARDS. In total, 400 (75.9%) patients were managed with invasive mechanical ventilation during their ICU stays. All ARDS patients received a tidal volume of 6.8 (5.8-7.9) mL/kg of their predicted body weight and a positive end-expository pressure (PEEP) of 8 (6-12) cmH 2 O. Recruitment manoeuvres (RMs) and prone positioning were used in 61 (15.3%) and 85 (16.1%) ventilated patients, respectively. Life-sustaining care was withdrawn from 92 (17.5%) patients. When these patients were included in the mortality analysis, 244 (46.3%) ARDS patients (16 (31.4%) with mild ARDS, 101 (40.4%) with moderate ARDS, and 127 (56.2%) with severe ARDS) died in the hospital.

Background: High-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are important treatment approaches for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the differential impact of HFNC versus NIV on clinical outcomes of COVID-19 is uncertain. Objectives: We assessed the effects of HFNC versus NIV (interface or mode) on clinical outcomes of COVID-19. Methods: We searched PubMed, EMBASE, Web of Science, Scopus, MedRxiv, and BioRxiv for randomized controlled trials (RCTs) and observational studies (with a control group) of HFNC and NIV in patients with COVID-19-related AHRF published in English before February 2022. The primary outcome of interest was the mortality rate, and the secondary outcomes were intubation rate, PaO2/FiO2, intensive care unit (ICU) length of stay (LOS), hospital LOS, and days free from invasive mechanical ventilation [ventilator-free day (VFD)]. Results: In all, 23 studies fulfilled the selection criteria, and 5354 patients were included. The mortality rate was higher in the NIV group than the HFNC group [odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.51–0.84, p = 0.0008, I2 = 60%]; however, in this subgroup, no significant difference in mortality was observed in the NIV-helmet group (OR = 1.21, 95% CI: 0.63–2.32, p = 0.57, I2 = 0%) or NIV-continuous positive airway pressure (CPAP) group (OR = 0.77, 95% CI: 0.51–1.17, p = 0.23, I2 = 65%) relative to the HFNC group. There were no differences in intubation rate, PaO2/FiO2, ICU LOS, hospital LOS, or days free from invasive mechanical ventilation (VFD) between the HFNC and NIV groups. Conclusion: Although mortality was lower with HFNC than NIV, there was no difference in mortality between HFNC and NIV on a subgroup of helmet or CPAP group. Future large sample RCTs are necessary to prove our findings. Registration: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022321997).

Mineral dust-induced gene (mdig) is a novel lung cancer-related oncogene. The aim of this study was to explore the effects of mdig on angiogenesis and lymphangiogenesis by vascular endothelial growth factor (VEGF) in lung adenocarcinoma. mdig-overexpressing A549, H1299 and 293T cells, mdig-silenced A549, human umbilical vein endothelial cells (HUVECs) and human lymphatic endothelial cells (HLECs) were cultured under normoxic and hypoxic conditions. Protein expression levels of mdig, epidermal growth factor receptor (EGFR), phospho(p)-EGFR Tyr1068, hypoxia-inducible factor-1α (HIF-1α), VEGF-A/C/D and VEGF-R1/R2/R3 were assessed using western blotting. mRNA expression levels of mdig, EGFR and HIF-1α were measured using RT-qPCR. Tube formation and xenograft tumor experiments were performed to examine the mechanism of mdig in angiogenesis and lymphangiogenesis. Protein expression levels of EGFR, HIF-1α and VEGF-A/C/D were significantly upregulated in cells cultured under hypoxic conditions compared with those cultured under normoxic conditions, whereas the levels of mdig were decreased. Protein expression levels of EGFR, p-EGFR and VEGF-A/R1/R2 were significantly increased in the mdig-overexpressing cells, whereas the levels of HIF-1α and VEGF-C/D/R3 were decreased compared with those in control cells, all of which were reversed in mdig-silenced cells. Tumor volumes and density of angiogenesis in the mdig-overexpressing group were significantly increased compared with those in the control group, whereas the density of lymphangiogenesis was decreased. No tumors formed in the mdig-silenced group after 3 weeks of assessment in vivo. Protein expression levels of EGFR, p-EGFR, VEGF-A and angiogenesis density were significantly reduced in the mdig-overexpressing cells treated with an EGFR inhibitor, whereas the levels of HIF-1α, VEGF-C/D and the lymphangiogenesis density were significantly increased in mdig-overexpressing cells treated with a HIF-1α agonist. All changes in protein expression were reversed in EGFR agonist and HIF-1α inhibitor treated mdig-silenced cells. In conclusion, mdig is an oxygen-sensitive protein that promotes tumor growth and angiogenesis by activating the EGFR/p-EGFR/VEGF-A/VEGF-R1/R2 pathway and inhibits lymphangiogenesis by blocking the HIF-1α/VEGF-C/D/VEGF-R3 pathway.

Recent studies have indicated that mineral dust-induced gene (MDIG) is an oncogene induced by environmental factors, which has a key role in the development and progression of various tumor types, through epigenetic modifications; however, there are no previous pan-cancer analyses of MDIG. In the present study, a comprehensive pan-cancer analysis of MDIG was performed using public databases. The results demonstrated that MDIG was upregulated in tumor tissue samples compared with normal tissue, that it was present in all cancer cell lines and it was closely associated with the prognosis of patients with different tumor types. Furthermore, MDIG expression was closely associated with the immunological characteristics of the tumor microenvironment (TME), such as the frequency of tumor-infiltrating immune cells, TME-relevant signatures, immunostimulatory genes, immune checkpoint genes, chemokine receptor genes, tumor mutational burden and microsatellite instability. In parallel, high expression of MDIG was associated with improved overall survival of patients and this was verified in a cohort of patients who had received anti-programmed cell death 1 ligand 1 treatment. Furthermore, high expression of MDIG led to multiple drug resistance in The Cancer Genome Atlas-lung adenocarcinoma cohort. In addition, gene set variant analysis and gene set enrichment analysis indicated that MDIG was involved in cell cycle regulation. In vitro experiments suggested that MDIG promoted cell proliferation through the mTOR complex 2/Akt and pyruvate dehydrogenase kinase 1/Akt signaling pathways. In summary, the present study suggests that MDIG may be a prognostic biomarker and therapeutic target for various cancer types.