Novel Patterns in High-Resolution Computed Tomography in Whipple Pneumonia.

With the use of metagenomic next-generation sequencing, patients diagnosed with Whipple pneumonia are being increasingly correctly diagnosed. We report a series of 3 cases in China that showed a novel pattern of movable infiltrates and upper lung micronodules. After treatment, the 3 patients recovered, and lung infiltrates resolved.

A novel multimodal prediction model based on DNA methylation biomarkers and low-dose computed tomography images for identifying early-stage lung cancer.

Objective: DNA methylation alterations are early events in carcinogenesis and immune signalling in lung cancer. This study aimed to develop a model based on short stature homeobox 2 gene (SHOX2)/prostaglandin E receptor 4 gene (PTGER4) DNA methylation in plasma, appearance subtype of pulmonary nodules (PNs) and low-dose computed tomography (LDCT) images to distinguish early-stage lung cancers. Methods: We developed a multimodal prediction model with a training set of 257 individuals. The performance of the multimodal prediction model was further validated in an independent validation set of 42 subjects. In addition, we explored the association between SHOX2/PTGER4 DNA methylation and driver gene mutations in lung cancer based on data from The Cancer Genome Atlas (TCGA) portal. Results: There were significant differences between the early-stage lung cancers and benign groups in the methylation levels. The area under a receiver operator characteristic curve (AUC) of SHOX2 in patients with solid nodules, mixed ground-glass opacity nodules and pure ground-glass opacity nodules were 0.693, 0.497 and 0.864, respectively, while the AUCs of PTGER4 were 0.559, 0.739 and 0.619, respectively. With the highest AUC of 0.894, the novel multimodal prediction model outperformed the Mayo Clinic model (0.519) and LDCT-based deep learning model (0.842) in the independent validation set. Database analysis demonstrated that patients with SHOX2/PTGER4 DNA hypermethylation were enriched in TP53 mutations. Conclusions: The present multimodal prediction model could more efficiently distinguish early-stage lung cancer from benign PNs. A prognostic index based on DNA methylation and lung cancer driver gene alterations may separate the patients into groups with good or poor prognosis.

Intermittent hypoxia-induced METTL3 downregulation facilitates MGLL-mediated lipolysis of adipocytes in OSAS.

Intermittent hypoxia (IH) is the core pathological feature of obstructive sleep apnea syndrome (OSAS), and insulin resistance (IR) is the most common metabolic complication of OSAS. Studies have shown that the levels of free fatty acids (FFAs), which are mainly released from adipocytes by lipolysis, are elevated in OSAS and play an important role in the development of IR. However, whether and how IH regulates adipocyte lipolysis in OSAS is not clear. Here, we revealed that the apnea hypopnea index was positively correlated with the serum levels of FFAs and FFA release from adipocytes in OSAS. In addition, IH facilitated lipolysis and FFA release from adipocytes by downregulating the level of METTL3. METTL3 downregulation impaired N6-methyladenosine (m6A) levels in MGLL mRNA and reduced MGLL expression, thereby promoting lipolysis. In addition, we identified YTHDF2 as the m6A reader that interacts with MGLL mRNA, accelerating its degradation. Furthermore, our data showed reduced levels of METTL3 and elevated levels of MGLL in the adipose tissues of OSAS patients and indicated an effect of METTL3 on lowering FFA levels and improving IR in rats with chronic IH. In conclusion, our study provides new insights into the development and treatment of IR in OSAS.

Expression of sirtuin type 3 in locus ceruleus is associated with long-term intermittent hypoxia-induced neurocognitive impairment in mice.

Recent studies revealed that increased oxidative stress is one of the major mechanisms underlying the cognitive dysfunction induced by long-term intermittent hypoxia (LTIH). Locus ceruleus (LC) neurons, which fire at high rate across wakefulness, are essential for optimal cognitive function. The aim of this study was to investigate whether sirtuin type 3 (SirT3), a redox responses coordinator, plays a role in LTIH-induced neurocognitive impairment. Mice were subjected to LTIH or room air [normal control (NC)] for 10 weeks (10 h/day). Morris water maze test was used to detect spatial learning and memory ability. The oxidative stress was evaluated through the level of superoxide dismutase 2 (SOD2) and dihydroethidium and ethidium (DHE). Then the correlation between the number of platform crossing and SirT3 content measured by western blot was analyzed. Results showed that performance on the Morris water maze test was significantly worse for LTIH mice than for NC mice. LTIH exposure downregulated SirT3 and SOD2 in LC neurons, increasing DHE immunodensity. In addition, the SirT3 protein levels in LC neurons were positively related to the number of platform crossing. These observations suggest that SirT3-SOD2-intracellular superoxide is a key component associated with the cognitive dysfunction induced by LTIH. Moreover, they lend support to a rational basis for targeting upregulation of SirT3 in LC as a disease modifying strategy.Video abstract: http://links.lww.com/WNR/A577.