Defective modulation of LINE-1 retrotransposition by cancer-associated SAMHD1 mutants.

Long interspersed nuclear elements (LINE-1) is now considered as the only active autonomous mobile DNA in humans, LINE-1 retrotransposition activities are associated with and fluctuate during cancer initiation and progression; however, the mechanism underlying the increased LINE-1 activity in cancer is poorly understood. SAMHD1 has been reported to be a potent inhibitor of LINE-1 retrotransposition, and SAMHD1 mutations are frequently associated with cancer development. To gain insights on whether cancer-related SAMHD1 mutants affect LINE-1 activity, we explored the biochemical and cellular properties of some human mutants known correlate with the development of cancer. Most of the tested SAMHD1 cancer-related mutations were defective in LINE-1 inhibition. Interestingly we also found that SAMHD1 mutant K288T was defective for dNTPase activity but showed potent activity against LINE-1 retrotransposition. These findings suggest that LINE-1 inhibition does not depend solely on the dNTPase activity of SAMHD1. In contrast, SAMHD1's ability to inhibit ORF2p-mediated LINE-1 RNP reverse transcription was correlated with SAMHD1-mediated LINE-1 inhibition. Together, our data could also facilitate the deeper understanding for the inhibition of endogenous LINE-1 elements by SAMHD1.

Clinical diagnosis and treatment of seven patients diagnosed pneumonia caused by Chlamydia abortus: a case series report.

Background: Chlamydia abortus pneumonia is very rare in normal people. At present, there is a lack of clinical data on the clinical characteristics and diagnosis and treatment experience of patients with this type of infection. Our team had recently treated 7 cases of these patients. This study aims to comprehensively summarize and analyze the clinical characteristics and treatment methods of Chlamydia abortus pneumonia, and to provide clinical evidence for the diagnosis and treatment of Chlamydia abortus pneumonia. Methods: Clinical data were retrospectively collected from patients diagnosed with Chlamydia abortus pneumonia through metagenomic next-generation sequencing (mNGS) at the Department of Pulmonary and Critical Care Medicine, Meizhou People's Hospital. Results: Seven patients with Chlamydia abortus pneumonia reported a history of poultry exposure, experiencing fever alongside respiratory or digestive symptoms. Marked elevation of blood inflammation markers, accompanied by hypoproteinemia and liver damage, was observed. Chest CT scans revealed pneumonia and pleural effusion. Chlamydia abortus was detected in blood or bronchoalveolar lavage fluid (BALF) through mNGS, often co-occurring with Chlamydia psittaci or other bacteria infections. Notably, Doxycycline demonstrated efficacy in treating Chlamydia abortus. Conclusion: Chlamydia abortus infection is a zoonotic disease, particularly among individuals with a history of poultry exposure, and mNGS emerges as a reliable diagnostic tool for its detection. Chlamydia abortus infection manifests with systemic and lung inflammation, effectively addressed through Doxycycline therapy.

Diagnostic value of loop-mediated isothermal amplification in detecting lower respiratory pathogens.

INTRODUCTION: To investigate the diagnostic value of loop-mediated thermostatic amplification (LAMP) in detecting pathogenic bacteria from bronchoalveolar lavage fluid (BALF) of patients with pulmonary disorders combined with lower respiratory tract infections (LRTI). METHODOLOGY: This cross-sectional study included patients with pulmonary disorders combined with LRTI, including chronic obstructive pulmonary disease (COPD), bronchiectasis, or lung cancer, hospitalized in Meizhou People's Hospital between January 2020 and October 2021. BALF was collected using local bronchoalveolar lavage and electronic bronchoscopy. The presence of the pathogens was confirmed using the LAMP method and the bacterial culture method. RESULTS: In total, 249 patients were included (135 with COPD, 73 with bronchiectasis, and 41 with lung cancer). The proportions of Methicillin-resistant Staphylococcus aureus (4.8% vs 0.4%, p = 0.02) and Haemophilus influenzae (6.8% vs 0.4%, p < 0.001) detected by the LAMP method was higher, while the proportion of Pseudomonas aeruginosa was lower compared with that of the culture method (6.8% vs 12.4%, p = 0.034). The bacterial species with the highest agreement coefficient was Stenotrophomonas maltophilia (Kappa = 0.798, p < 0.001). Furthermore, 9 COPD patients exhibited mixed infections as determined by the LAMP method, whereas the culture method detected only 2 of these cases (1.48%) (p < 0.05). CONCLUSIONS: LAMP can detect more pathogenic bacteria, notably Haemophilus influenza, Methicillin-resistant Staphylococcus aureus, and atypical pathogens in patients with clinically common pulmonary disorders combined with LRTI. LAMP may provide etiological evidence to guide the clinical use of antibiotics in primary hospitals.

Correlation of Luminal Mucus Score in Large Airways with Lung Function and Quality of Life in Severe Acute Exacerbation of COPD: A Cross-Sectional Study.

BACKGROUND AND OBJECTIVE: Luminal mucus plugging in small airways is associated with lung function decline and death of patients with chronic obstructive pulmonary disease (COPD). However, little attention has been paid to the possible role of mucus in large airways in acute exacerbation of COPD (AECOPD). Therefore, this study aimed to explore the relationship between the luminal mucus score of large airways and other physiological parameters of severe AECOPD. SUBJECTS AND METHODS: A total of 74 AECOPD inpatients were enrolled in this cross-sectional study. All patients underwent lung function tests and bronchoscopy, and their luminal mucus was observed and scored through bronchoscopy. Four questionnaires, including the St. George Respiratory Questionnaire (SGRQ), modified Medical Research Council dyspnea scale (mMRC), COPD Assessment Test (CAT) and Exacerbation of Chronic pulmonary disease Tool (EXACT), were used to assess health-related quality of life (HRQoL). RESULTS: The luminal mucus score of large airways was significantly correlated with spirometry parameters and HRQoL score. Both mMRC grade and SGRQ score were significantly positively correlated with luminal mucus score (ρ=0.527, P<0.001; ρ=0.441, P<0.001, respectively). Forced expiratory flow at 25% to 75% of the FVC (FEF25%-75%) and FEV1% predicted, as functional measures reflecting small airway disease, were significantly negatively correlated with luminal mucus score (ρ=-0.518, P<0.001; ρ=-0.498, P<0.001, respectively). The stepwise multiple linear regression model suggested that mMRC grade and FEV1% predicted could predict luminal mucus score (R 2=0.348, F=18.960, P<0.001). CONCLUSION: For severe acute exacerbation of COPD, bronchoscopy-identified luminal mucus in large airways is associated with reduced lung function and worse health-related quality of life.