Psittacosis caused severe community-acquired pneumonia accompanied by acute hypoxic respiratory failure: a multicenter retrospective cohort study from China.

INTRODUCTION: Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF). METHODS: This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods. RESULTS: This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO2/FiO2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline. CONCLUSION: Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative.

Expression and Related Mechanisms of miR-100 and TRIB2 in COPD Patients.

Background: Chronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases in the world. COPD is a general term for a class of lung diseases, including emphysema, chronic bronchitis, and refractory asthma. It is characterized by irreversible airflow obstruction and chronic tracheal inflammation. Objective: This study aimed to investigate the expression and related mechanisms of miR-100 and TRIB2 in patients with COPD. Methods: We collected the serum of patients admitted to our hospital and healthy volunteers undergoing physical examination at the same time, pulmonary fibroblasts were purchased for the experiments, miR-100 was overexpressed, and TRIB2 expression was inhibited in cells. The miR-100 and TRIB2 expression levels in serum and cells were detected by qRT-PCR and Western blot, cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, and the relationship between miR-100 and TRIB2 was explored by the dual-luciferase report. Results: The miR-100 expression in the serum of the COPD group was expressed normally, while the TRIB2 expression was expressed abnormally (p < 0.05). The AUC of serum miR-146a and TRIB2 for COPD diagnosis were 0.965 and 0.954, respectively. Overexpressing miR-100 and inhibiting the TRIB2 expression could decrease cell proliferation and increase apoptosis rate. According to the dual-luciferase report, miR-100 and TRIB2 had a targeted regulatory relationship. Rescue experiments showed that overexpressing TRIB2 could reverse the changes of cell proliferation and apoptosis caused by overexpression of miR-100. Conclusion: miR-100 and TRIB2 were expressed abnormally in serum of COPD patients, and miR-100 could inhibit proliferation of pulmonary fibroblasts and promote their apoptosis.

MicroRNA-140-3p represses the proliferation, migration, invasion and angiogenesis of lung adenocarcinoma cells via targeting TYMS (thymidylate synthetase).

MicroRNA (miR)-140-3p has been proved to repress lung adenocarcinoma (LUAD), and our study aims to further evaluate the mechanism. Bioinformatic analyses were performed. The viability, proliferation, migration, invasion and angiogenesis of transfected LUAD cells were all determined via Cell Counting Kit-8, colony formation, Scratch, Transwell, and tube formation assays. The targeting relationship between miR-140-3p and thymidylate synthetase (TYMS) was confirmed by dual-luciferase reporter assay. Relative expressions of miR-140-3p, TYMS, epithelial-to-mesenchymal transition- (E-cadherin, N-cadherin, vimentin), angiogenesis- (vascular endothelial growth factor (VEGF)), and apoptosis-related factors (cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax)) were quantified by quantitative real-time polymerase chain reaction or Western blot. TYMS was high-expressed yet miR-140-3p was low-expressed in LUAD cells. Upregulation of miR-140-3p inhibited TYMS expression, viability, colony formation, migration, invasion, and tube length within LUAD cells, while downregulation of miR-140-3p did oppositely. Silenced TYMS, the downstream target gene of miR-140-3p, reversed the effects of miR-140-3p downregulation on TYMS expression, cell viability, colony formation, migration, invasion, and tube length as well as the metastasis-, apoptosis- and angiogenesis-related proteins in LUAD cells. Upregulation of miR-140-3p inhibited the proliferation, migration, invasion and angiogenesis of LUAD cells via targeting TYMS.

Clinical features related to hospital expenses for non-cystic fibrosis bronchiectasis in China.

OBJECTIVE: Bronchiectasis is a common chronic airway disease. We investigated the economic burden and associated factors of bronchiectasis in China. METHODS: In this multicenter retrospective cohort study, we reviewed medical records of patients admitted to 18 tertiary hospitals during 2010 to 2014 with a bronchiectasis-related diagnosis. RESULTS: A total 5469 patients with bronchiectasis were admitted, accounting for 3.13% ± 1.80% of all discharged patients with any diagnosis during the same period; 13 patients died upon discharge. The median hospitalization cost was RMB 8421.52 (RMB 5849.88-12,294.47). Risk factors associated with hospitalization costs included age at admission (>70 vs. <40 years, odds ratio (OR) = 1.221, 95% confidence interval (CI) = 1.082-1.379; >80 vs. <40 years, OR = 1.251, 95% CI = 1.089-1.438), smoking (≤15 packs/year vs. non-smokers, OR = 1.125, 95% CI = 1.006-1.271; >15 packs/year vs. non-smokers, OR = 1.127, 95% CI = 1.062-1.228), length of hospitalization (OR = 1.05, 95% CI = 1.046-1.054), combination antibiotic treatment (OR = 1.089, 95% CI = 1.033-1.148), cough (OR = 0.851, 95% CI = 0.751-0.965), dyspnea (OR = 0.93, 95% CI = 0.878-0.984), chronic obstructive pulmonary disease (OR = 0.935, 95% CI = 0.878-0.996), respiratory failure (OR = 0.923, 95% CI = 0.862-0.989), cor pulmonale (OR = 0.919, 95% CI = 0.859-0.982), and death (OR = 1.816, 95% CI = 1.113-2.838). CONCLUSIONS: Age, smoking status, symptoms, and respiratory comorbidities were associated with hospitalization costs of bronchiectasis.

Mir-29b mediates the regulation of Nrf2 on airway epithelial remodeling and Th1/Th2 differentiation in COPD rats.

COPD, or Chronic obstructive pulmonary disease, is an inflammation-related disease and lead to cachexia and muscle wasting. Altered nuclear factor erythroid 2-related factor 2 (Nrf2) expression is found in patients of COPD because it is involved in pulmonary protective effects. MiR-29b could be activated by Nrf2. We hypothesized that miR-29b might mediate the regulation of Nrf2 on Th1/Th2 differentiation and airway epithelial remodeling in COPD rats. SD rats were exposed to smoke for COPD induction. Expression of Nrf2 mRNA and miR-29b in lung tissues was quantified. Expression of Nrf2 and matrix metalloproteinase 2 (MMP2) were also detected by immunohistochemistry and western blot. Th1 markers and Th2 markers were measured by ELISA in peripheral blood. Flow cytometry was used to detect the Th1/Th2 ratio. miR-29b and Nrf2 was manipulated at mRNA level in A549 cells using transfection. Cellular growth and migration were measured in transfectants. In lung tissues of COPD rats, expression of Nrf2 and miR-29b decreased. MMP2, a target of miR-29b, had an opposite expression to miR-29b in peripheral blood. Levels of inflammatory factors and Th1/Th2 ratio increased. MiR-29b mediated the regulation of Nrf2 on remodeling of lung epithelial cells. Blocking Nrf2 expression in A549 cells led to the opposite expression of miR-29b and further decreased MMP2 production; meanwhile, cell growth and motility were improved. Different miR-29b levels affected MMP2 expression and cellular characteristics. The findings suggested that miR-29b was a regulator the pathological progress of COPD. It mediates the effect of Nrf2 on Th1/Th2 differentiation and on remodeling process of airway epithelial cells.

Microarray profiles reveal that circular RNA hsa_circ_0007385 functions as an oncogene in non-small cell lung cancer tumorigenesis.

OBJECTIVE: Circular RNAs (circRNAs) are a novel class of non-protein-coding RNA. Emerging evidence indicates that circRNAs participate in the regulation of many pathophysiological processes. This study aims to explore the expression profiles and pathological effects of circRNAs in non-small cell lung cancer (NSCLC). METHODS: Human circRNAs microarray analysis was performed to screen the expression profile of circRNAs in NSCLC tissue. Expressions of circRNA and miRNA in NSCLC tissues and cells were quantified by qRTPCR. Functional experiments were performed to investigate the biological functions of circRNA, including CCK-8 assay, colony formation assay, transwell assay and xenograft in vivo assay. RESULTS: Human circRNAs microarray revealed a total 957 abnormally expressed circRNAs (> twofold, P < 0.05) in NSCLC tissue compared with adjacent normal tissue. In further studies, hsa_circ_0007385 was significantly up regulated in NSCLC tissue and cells. In vitro experiments with hsa_circ_0007385 knockdown resulted in significant suppression of the proliferation, migration and invasion of NSCLC cells. In vivo xenograft assay using hsa_circ_0007385 knockdown, significantly reduced tumor growth. Bioinformatics analysis and luciferase reporter assay verified the potential target miR-181, suggesting a possible regulatory pathway for hsa_circ_0007385. CONCLUSION: In summary, results suggest hsa_circ_0007385 plays a role in NSCLC tumorigenesis, providing a potential therapeutic target for NSCLC.

Crocin reduces Aspergillus fumigatus-induced airway inflammation and NF-κB signal activation.

Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammation and its exacerbation is often accompanied by Aspergillus fumigatus (A. fumigatus) infection. Increasing evidences demonstrated the potent antioxidant and -inflammatory effects of crocin. However, the role of crocin in A. fumigatus-induced inflammation is still unknown. We aimed to evaluate the role of crocin in inflammation response induced by A. fumigatus in human bronchial epithelial cells and the possible mechanisms. BEAS-2B and NHBE cells were pretreated with crocin for 24 h, and then A. fumigatus conidia were added for 24 h. A. fumigatus treatment exhibited a significant higher TNF-α, IL-8, IL-6, and IL-1ß level (P < 0.05), whereas crocin pretreatment significantly inhibited A. fumigatus induced the pro-inflammatory cytokines (P < 0.05). NF-κB inhibitor PDTC inhibited pro-inflammatory cytokines release triggered by A. fumigatus (P < 0.05). Furthermore, crocin suppressed A. fumigatus induced NF-κB p65 nuclear translocation, the phosphorylation of IKKα and IκBα, the degradation of IκBα and NF-κB reporter activity. Crocin pretreatment also resulted in an inhibition of A.fumigatus-induced ROS production (P < 0.05). Taken together, these results indicate that crocin may prevent A. fumigatus-induced inflammation through suppressing NF-κB signal pathway.

Polymorphisms of -800G/A and +915G/C in TGF-ß1 gene and lung cancer susceptibility.

We studied the relationship between the polymorphisms of -800G/A and +915G/C in transforming growth factor-ß1 (TGF-ß1) gene and lung cancer susceptibility. The sequence-specific primer polymerase chain reaction (PCR-SSP) technique was used to test 156 non-small cell lung cancer (NSCLC) patients that were selected as the observation group and 156 patients with pneumonia and tuberculosis that were selected as the control group (age and gender 1:1 proximal matching principle) and the polymorphisms of the first exon -800G/A and +915G/C TGF-ß1 genes. The expression of TGF-ß1 levels in peripheral blood was detected using ELISA. The proportion of -800G/A gene AA subtype and A allelic gene in the observation group was significantly higher than that in the control group, while the proportion of +915G/C gene CC subtype and C allelic gene was also significantly higher than that in the control group (P<0.05). The cancer risk [odds ratio (OR)] of patients with A allelic gene in -800G/A gene was 4.8 (95% CI=2.563-6.537, P<0.05), while the cancer risk (OR) of patients with C allelic gene in +915G/C gene was 4.7 (95% CI=2.317-5.864, P<0.05). The serum TGF-ß1 expression levels of -800G/A gene AA subtype in the observation group was significantly higher than the GG type, GA type and the control group, while the TGF-ß1 level of +915G/C gene CC subtype was significantly higher than the GG type, GC type and the control group (P<0.05). Therefore, the polymorphisms of -800G/A and +915G/C in TGF-ß1 gene are closely related to the lung cancer susceptibility.

MicroRNA-194 restrains the cell progression of non-small cell lung cancer by targeting human nuclear distribution protein C.

NSCLC accounts for over 80% of all lung cancers and is associated with poor prognosis. Human nuclear distribution C (hNUDC) was predicted to be the target gene of microRNA-194 (miR-194). The present study was designed to demonstrate the mechanism of miR-194 in the regulation of non-small cell lung cancer (NSCLC) via targeting the hNUDC. The hNUDC expression was found to strongly be increased while the miR-194 decreased significantly in the NSCLC cell lines when compared with the healthy controls. Moreover, the luciferase report confirmed the targeting reaction between miR-194 and hNUDC. After transfection with miR-194 mimic into NSCLC cells, we found that the miR-194 overexpression resulted in abnormal nuclear division, decreased cell proliferation and inhibited the expression of hNUDC and Mpl/ERK pathway proteins. Furthermore, the hNUDC overexpression affected the suppression effect of miR-194 in 95D cells, indicating that miR-194 suppresses tumor cell process by inhibiting the hNUDC expression. In brief, the present study suggests that the upregulation of miR-194 affects the hNUDC expression, leading to a downregulated expression of Mpl/ERK pathway proteins, and suppresses the mitosis and proliferation of NSCLC cells. These results offer a potential therapeutic strategy for the treatment of lung cancer.

[Clinical features of severe new influenza A (H1N1) in pregnant women].

OBJECTIVE: To investigate the clinical characteristics of severe influenza A (H1N1) in pregnant women. METHODS: Sixteen patients with severe pneumonia caused by influenza A (H1N1) were included in this study from November 26 to December 20, 2009. RESULTS: All of the sixteen patients were young women, and 15 of them were pregnant. Leukopenia was observed in 2 cases of the 16 patients, and lymphopenia in 14 cases. Data on the ratio of CD(4) cells to CD(8) cells were available for 12 patients, and 7 cases of whom had an abnormal CD(4)/CD(8) ratio (< 1.4). Eleven of the 15 patients had increased serum lactate dehydrogenase levels, which were above 245 U/L. Three patients had elevated creatine kinase levels at admission. Five cases of the 16 patients had decreased serum potassium levels, which were below 3.5 mmol/L. Four patients had C(4) levels greater than 36 mg per deciliter, and 4 cases had C(3) less than 75 mg per deciliter. All 16 patients had radiologically confirmed pneumonia with bilateral patchy alveolar opacities, affecting 3 or 4 lung quadrants. Findings on chest radiographs were consistent with acute respiratory distress syndrome in all patients requiring mechanical ventilation. A small amount of pleural effusion was found in 4 cases, and pericardial effusion was found in 1 of them. Respiratory distress requiring intubation and mechanical ventilation developed in 9 pregnant patients within the first 24 hours after admission, and 2 of them in the third trimester died, while 7 patients for whom pregnancy was timely terminated recovered. CONCLUSIONS: Pregnant women with 2009 pandemic influenza A (H1N1) appear to have an increased risk of severe disease characterized by severe pneumonia and respiratory failure. Early anti-viral therapy, early termination of pregnancy, and timely mechanical ventilation may bring clinical benefits to pregnant patients.