[Effects of helium-oxygen mechanical ventilation on inflammatory response of diseased lung segments and diaphragm function in patients with pneumonia].

OBJECTIVE: To investigate the clinical effect of helium-oxygen mechanical ventilation on inflammation of the diseased lung segment and diaphragm function in patients with acute respiratory distress syndrome (ARDS) caused by pneumonia who suffered difficulty weaning from mechanical ventilation. METHODS: A prospective controlled study was conducted. A total of 40 patients with ARDS caused by pneumonia and requiring tracheal intubation with difficulty weaning from mechanical ventilation, admitted to the department of critical care medicine in Pingtan Branch of Fujian Medical University Union Hospital from October 2020 to December 2021 were enrolled. Patients were divided into nitrogen oxygen ventilation group and helium-oxygen ventilation group according to random number table, with 20 cases in each group. The nitrogen oxygen ventilation group was given 60% nitrogen and 40% oxygen ventilation treatment, and the helium-oxygen ventilation group was given 60% helium and 40% oxygen ventilation treatment. Peak airway pressure (Ppeak), plateau airway pressure (Pplat), tidal volume (VT), minute ventilation volume (MV) and pulse oxygen saturation (SpO2) were collected at 0, 1, 2, 3 hours after ventilation treatment. At the same time, the concentrations of inflammatory factors interleukin-6 (IL-6) and C-reactive protein (CRP) in epithelial lining fluid in patients with diseased lung segments were measured before and after ventilation treatment for 3 hours, and the diaphragmatic excursion and the diaphragmatic thickening fraction were measured before and after ventilation treatment for 3 hours. RESULTS: There were no significant differences in gender, age, oxygenation index, serum CRP, serum procalcitonin (PCT), body temperature, serum creatinine (SCr), alanine aminotransferase (ALT), fasting blood glucose (FPG), hemoglobin (Hb), and basic heart and lung diseases between the two groups. Under the condition that VT and SpO2 are relatively unchanged, the airway pressure in helium-oxygen ventilation group decreased significantly after 1 hour of ventilation [Ppeak (cmH2O, 1 cmH2O≈0.098 kPa): 22.80±4.47 vs. 28.00±5.07, Pplat (cmH2O): 19.15±3.90 vs. 23.20±3.81, both P < 0.05], and the airway pressure in the nitrogen oxygen ventilation group increased significantly after 1 hour [Ppeak (cmH2O): 22.35±2.13 vs. 19.75±1.94, Pplat (cmH2O): 18.50±1.70 vs. 16.50±1.88, both P < 0.05]. There were no significant differences in CRP and IL-6 levels in epithelial lining fluid in the diseased lung segment before and after ventilation in the nitrogen oxygen ventilation group, while the levels of these indexes in the helium-oxygen ventilation group after ventilation were significantly lower than those before ventilation, and significantly lower than those in the nitrogen oxygen ventilation group [CRP (mg/L): 10.15 (6.39, 15.84) vs. 16.10 (11.63, 18.66), IL-6 (µg/L): 1.15 (0.78, 1.86) vs. 2.67 (1.67, 4.85), both P < 0.05]. There were no statistically significant differences in the diaphragmatic excursion and the diaphragmatic thickening fraction before and after ventilation in the nitrogen oxygen ventilation group, while the above indexes in the helium-oxygen ventilation group were significantly higher than those before ventilation, and were significantly higher than those in the nitrogen oxygen ventilation group [diaphragmatic excursion (cm): 1.93 (1.69, 2.20) vs. 1.34 (1.22, 1.83), diaphragmatic thickening fraction: (48.22±8.61)% vs. (33.29±11.04)%, both P < 0.05]. CONCLUSIONS: Helium-oxygen ventilation can reduce the airway pressure of patients with mechanical ventilation, alleviate the inflammatory response of lung segment, improve the function of respiratory muscle, and is expected to be an important treatment for severe lung rehabilitation.

Improvement of cardiac function by mesenchymal stem cells derived extracellular vesicles through targeting miR-497/Smad7 axis.

BACKGROUND: The extracellular vesicles (EVs) secreted by bone marrow mesenchymal stromal cells (MSCs) have the ability to improve Myocardial infarction (MI). Some microRNAs (miRNAs) including miR-497 and related target genes have been proved to be closely linked with heart diseases. However, EVs could regulate MI process through miR-497, and the mechanisms have not been fully reported. METHODS: Ligation of left anterior descending artery was performed to established MI animals model. Hypoxia cell model was established through lowering the level of oxygen. The cell invasion, migration, and proliferation were measured using tanswell, wound heating, and MTT assays. HE, Masson trichrome, and Sirius Red staining were used to investigate the morphological changes. RESULTS: Overexpression of miR-497 reversed the promotion of cell migration, invasion, and proliferation caused by EVs. The improvement of cardiac function induced by EVs could also be reversed by overexpression of miR-497. Direct binding site between Smad7 and miR-497 was identified. Knockdown of Smad7 reversed the improvement of cardiac function induced by EVs. CONCLUSIONS: We found that EVs isolated from MSCs might improve the cardiac injury caused by MI through targeting miR497/Smad7. This study provides novel potential therapeutic thought for the prevention and treatment of MI through targeting miR-497/Smad7.

MicroRNA-127-5p attenuates severe pneumonia via tumor necrosis factor receptor-associated factor 1.

Pneumonia is a persistent and pervasive disease, the effects of which can be severe. MicroRNA (miR)-127-5p has been utilized as a novel biomarker for the diagnosis of severe pneumonia. The present study aimed to investigate the function of miR-127-5p during severe pneumonia. An in vitro model of severe pneumonia in Ana-1 murine macrophages was established using lipopolysaccharide (LPS). Subsequently, reverse transcription-quantitative PCR and ELISA were performed to detect the mRNA and protein expression levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α. Western blotting was also performed to measure the activity of AKT and NF-κB. The results indicated that compared with the control group, LPS treatment increased TNF receptor-associated factor 1 (TRAF1) expression levels and reduced miR-127-5p expression levels. Furthermore, the results revealed that the 3'-untranslated region of TRAF1 was targeted by miR-127-5p. miR-127-5p mimic reduced LPS-induced increases in IL-1ß, IL-6 and TNF-α expression by targeting TRAF1, which was potentially mediated by inactivation of the AKT and NF-κB signaling pathways. Collectively, the results demonstrated that miR-127-5p may attenuate severe pneumonia by reducing LPS-induced inflammatory cytokine production, and inactivating the AKT and NF-κB signaling pathways by targeting TRAF1.

Morusin alleviates mycoplasma pneumonia via the inhibition of Wnt/ß-catenin and NF-κB signaling.

Morusin has been traditionally used for the treatment of Mycoplasma pneumoniae pneumonia (MPP), but the underlying mechanism remains elusive. The present study aimed to explore the mechanism by which morusin achieves efficacy on mycoplasma pneumonia. Mycoplasma pneumonia model was established in BALB/c mouse and the effects of morusin were evaluated in the model. Compared with the model group, DNA amount of M. pneumoniae decreased by 24.6 ± 3.14% and 47.6 ± 6.78% in low morusin (20 mg/kg) and high morusin (50 mg/kg) groups, respectively (P<0.05). Moreover, morusin treatment led to decreased levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor α and increased level of anti-inflammatory IL-10 in mice lung tissue. Furthermore, morusin treatment inhibited the activation of Wnt/ß-catenin and NF-κB pathways in mice lung tissue. Taken together, our results suggest that morusin relieves mycoplasma pneumonia via the inhibition of the activation of Wnt/ß-catenin and NF-κB pathways, and is a potential natural agent for the treatment of mycoplasma pneumonia.

Clinicopathologic features and prognostic implications of MYBL2 protein expression in pancreatic ductal adenocarcinoma.

MYBL2 (B-MYB), a member of the MYB family of transcription factor genes, regulates the expression of genes in the process of tumorigenesis. Many studies have shown that MYBL2 is high expresssion in several human malignancies including pancreatic ductal adenocarcinoma (PDAC). However, its role in PDAC is still unclear. The present study is designed to investigate MYBL2 expression levels and prognostic significance in PDAC patients. We assessed MYBL2 expression level by immunohistochemistry in tumor tissues from 93 PDAC patients undergoing curative resection. The association of MYBL2 expression with clinicopathological parameters was evaluated by Pearson's chi-square (χ2) test, Fisher's exact test, and Spearman's rank. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of MYBL2 expression on survival. The expression of MYBL2 was significantly higher in PDAC cells compared with adjacent non-cancerous tissues (P=0.000). The overexpression of MYBL2 in the tumor tissues was significantly correlated with a higher T classification (p=0.002), peri-neural invasion (PNI) (p=0.013) and vital status (p=0.045). Kaplan-Meier analysis indicated that high MYBL2 expression was significantly associated with shorter overall survival times in PDAC patients. Moreover, univariate and multivariate analysis confirmed MYBL2 expression (P=0.010), histological grade (P=0.001) as independent prognostic factors in PDAC. These results suggested that overexpression of MYBL2 might serve as a novel prognostic biomarker in PDAC patients.