Close Relationship between cIAP2 and Human ARDS Induced by Severe H7N9 Infection.

BACKGROUND: cIAP2 is involved in necroptosis as a key upstream regulation factor. We aimed to investigate the role of cIAP2 in ARDS/ALI induced by H7N9 virus through regulating the RIPK1/3 necroptosis pathway. METHODS: Lung tissues of 11 patients who died from ARDS-complicated H7N9 infection between 2013 and 2016 were obtained as the H7N9-ARDS group. Lung tissues near benign lung nodules were acquired as the control group. Histological changes were evaluated by H&E staining. Protein levels of cIAP2, RIPK1, RIPK3, p-RIPK3, MLKL, and p-MLKL in the lung tissues were detected by Western Blot. The mRNA levels of cIAP2, RIPK1, and RIPK3 were detected by real-time PCR. RESULTS: H7N9 virus infection had a high mortality, with ARDS being the leading cause of death. The protein level of cIAP2 in the experimental group was lower than that in the control group (P<0.05). However, the experimental group showed higher RIPK1, RIPK3, and p-RIPK3 protein levels than the control group (P<0.05), as well as the expression level of MLKL and p-MLKL protein, which is a key downstream protein in necroptosis (P<0.05). CONCLUSION: In tissues from patients with fatal H7N9, downregulation of cIAP2 and induction of necroptosis was observed. We could speculate that necroptosis of the pulmonary epithelium is associated with severe H7N9 infection leading to ARDS. Thus, necroptosis inhibition may be a novel therapy for H7N9 influenza virus.

miR-371, miR-138, miR-544, miR-145, and miR-214 could modulate Th1/Th2 balance in asthma through the combinatorial regulation of Runx3.

Asthma is tightly related to the imbalance of Th1/Th2 cells, and Runx3 plays a pivotal role in the differentiation of T helper cells. The present study aimed to investigate dysregulated microRNAs that may target Runx3 in CD4+ T cells from asthmatic patients and reveal Runx3 function in Th1/Th2 balance regulation. We detected the levels of Th1- and Th2-related cytokines by ELISA and analyzed the differentiation marker gene of T helper cells by qRT-PCR. Results indicated that an imbalance of Th1/Th2 cells was present in our asthmatic subject. Runx3 expression was reduced in the CD4+ T cells from asthmatic patients. Overexpression of Runx3 could restore the Th1/Th2 balance. After performing microRNA microarray assay, we found a series of microRNAs that were considerably altered in the CD4+ T cells from asthmatic patients. Among these upregulated microRNAs, eight microRNAs that may target Runx3 were selected by bioinformatics prediction. Five microRNAs, namely miR-371, miR-138, miR-544, miR-145, and miR-214, were confirmed by qRT-PCR and selected as candidate microRNAs. Luciferase reporter assay showed that these five microRNAs could directly target the 3'-UTR of Runx3. However, only simultaneous inhibition of these five microRNAs could alter the expression of Runx3. Most importantly, only simultaneous inhibition could improve the Th1/Th2 balance. Thus, we suggest that miR-371, miR-138, miR-544, miR-145, and miR-214 can modulate the Th1/Th2 balance in asthma by regulating Runx3 in a combinatorial manner.

1,25-dihydroxyvitamin D3 reduces mouse airway inflammation of neutrophilic asthma by transcriptional modulation of interleukin-17A.

Corticosteroid resistance and severe airflow obstruction have been proved to participate in the neutrophilic inflammation of airway in uncontrollable asthmatics. IL-17 is one of the pro-inflammatory cytokines produced by Th17 cells, and it plays an important role in the neutrophilic inflammation of airway in steroid-resistant asthmatics. Recent data have proved that 1,25(OH)2D3 represses IL-17A in inflammation and Th17-mediated autoimmunity through vitamin D receptors(VDR) at the level of transcription. Our study validated that 1,25-(OH)2D3 can modulate IL-17A on the transcriptional level by using Runx1, thus reducing inflammation in the airway of mice with neutrophilic asthma. 1,25(OH)2D3 may be promising for the therapeutic applications of neutrophilic asthma.

[Diagnosis and treatment of pulmonary hypertension caused by sleep hypoventilation: analysis of 4 cases in a family].

OBJECTIVE: To summarize the experience in diagnosis and treatment of pulmonary hypertension caused by sleep hypoventilation. METHODS: The clinical data of 4 patients in a family with pulmonary hypertension caused by sleep hypoventilation, full brothers and sisters, 2 (Cases 1 and 2) being treated presently and 2 (Cases 3 and 4) being deceased and traced by family medical history, were retrospectively analyzed. RESULTS: Three of the 4 cases (cases 1, 3, and 4) were misdiagnosed as with cor pulmonale combined with pulmonary hypertension, and one case (case 2) was misdiagnosed as with primary pulmonary hypertension. Polysomnography (PSG) revealed alveolar hypoventilation-induced long period of oxygen desaturation at sleep in Cases 1 and 2, thus confirming the diagnosis. Pulmonary function test showed that the percentage of maximum inspiratory pressure (PImax) in predicted value (51.5% and 20.9%) and the maximum expiratory pressure (PEmax) in predicted value (51.3% and 29.6%) decreased, the percentage of mouth occlusion pressure (P0.1) in predicted value (141% and 133%) compensatively increased, and the respiratory muscle strength decreased in Cases 1 and 2, which suggested that there was neuromuscular disorder in these patients. Treated by noninvasive ventilation the symptoms of these 2 patients were improved and they were discharge at last. Subsequently, they were treated by long-term night noninvasive ventilation at home, and returned to normal work and life. During the follow-up for 22 and 12 months respectively after discharge, PSG showed that the alveolar hypoventilation-induced long period oxygen desaturation at sleep had been greatly improved, and echocardiogram showed that the pulmonary pressure was greatly decreased. CONCLUSION: For the patients with unexplained pulmonary hypertension, PSG monitoring and pulmonary function tests such as PImax, PEmax, and P0.1 help determine the etiology, and long-term night noninvasive ventilation at home can improve the outcome of sleep hypoventilation-induced pulmonary hypertension.

[Lung transplantation in the treatment of ventilator dependent end-stage lung diseases: report of three cases].

OBJECTIVE: To investigate the perioperative management, recipient selection of end-stage lung diseases dependent on ventilator, and the strategy of ventilator weaning. METHODS: Fifteen patients underwent lung transplantation in our hospital from 2002 to 2005. Of them, three were dependent on ventilator for 89, 120 and 107 days respectively because of end-stage pulmonary emphysema before operation. Single-lung transplantation was performed in one patient and sequential bilateral single-lung transplantations were performed in two patients without extracorporeal circulation. RESULTS: The three patients were weaned from ventilator in the sixth, eleventh and twenty second day respectively after operation. They were discharged from hospital 71 d, 41 d, and 67 d respectively after operation. They had been followed up for 22, 4, and 2 months respectively before this analysis. Their quality of life improved significantly. CONCLUSION: Lung transplantation is effective for the treatment of ventilator dependent end-stage lung diseases.