A Novel Mitochondrial-Related Gene Signature for the Tumor Immune Microenvironment Evaluation and Prognosis Prediction in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. More and more studies have reported that mitochondrial-related genes (MTRGs) were associated with the clinical outcomes of multiple tumors solely. In this study, we aimed to develop a novel prognostic model based on MTRGs. Differentially expressed MTRGs were identified from TCGA-LUAD and GSE31210 cohorts. Univariate Cox regression analysis was utilized to screen differentially expressed MTRGs that were related to prognosis of LUAD. Then, LASSO Cox regression analysis was used to develop a prognostic signature. ESTIMATE was used for estimating the fractions of immune cell types. In this study, we identified 44 overlapping differentially expressed MTRGs in TCGA-LUAD and GSE31210 cohorts. Among 44 overlapping differentially expressed MTRGs, nine genes were associated with prognosis of LUAD. When the penalty parameter lambda was the minimum, there were six genes meeting the conditions of constructing the signature, including SERPINB5, CCNB1, FGR MAOB, SH3BP5, and CYP24A1. The survival analysis suggested that prognosis of patients in the high-risk group was significantly worse than that in the low-risk group. Cox regression analyses showed that the risk score was an independent predictor of LUAD prognosis. As with the results of ESTIMATE score, the degree of immune cell infiltration in the low-risk group was higher than that in the high-risk group, such as TIL, Treg, and B cells. In addition, TMB and cancer stem cell infiltration were higher in the low-risk group than the high-risk group. In conclusion, we developed a novel MTRG signature acting as a negative independent prognostic factor. In the future, individualized treatments and medical decision-making may benefit from using the predicted model.

Comparison of Immediate and Sequential Withdrawal of a Systemic Glucocorticoid in the Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Parallel-Controlled, Open-Label Study.

Patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) were treated with immediate or sequential withdrawal after 5 days of systemic glucocorticoids. The effects of the two withdrawal methods on the prognosis of patients were compared at 30, 90, 180, and 360 days after discharge. A multicenter, randomized, double-blind, parallel-controlled, open-label study was conducted in the respiratory department of tertiary hospitals in Central China. Patients met inclusion criteria for AECOPD and needed to use systemic glucocorticoids. They were randomly assigned to immediate and sequential withdrawal groups at a 1:1 ratio. The study was completed in August 2020 and is registered at the China Clinical Trials Registry (Chictr.org) (ChiCTR1800018894). According to general data and clinical characteristics, there were no statistically significant differences between the 329 patients in the immediate withdrawal group and the 310 patients in the sequential withdrawal group (P > 0.05). At the 30, 90, 180, and 360-days follow-up, the acute exacerbation frequency, rehospitalization rate, mortality, and intensive care unit (ICU) treatment rate were not significantly different between the immediate withdrawal group and sequential withdrawal group (P > 0.05). The modified Medical Research Council (mMRC) and COPD assessment test (CAT) scores were also not significantly different between the two groups. At the 180- and 360-day follow-up, forced expiratory volume in 1 s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups (P > 0.05). The time from discharge to first acute exacerbation was significantly lower in the immediate withdrawal group (46.12 days) than in sequential withdrawal group (49.02 days) (P < 0.05). The time of stay in the hospital for the first time after discharge was not significantly different between the two groups (P > 0.05). Adverse events were not significantly different between the immediate withdrawal group and sequential withdrawal group (P < 0.05). Subgroup analysis was performed according to age, degree of disease, and relevant indicators. At the 30-day follow-up, the acute exacerbation frequency of patients with advanced age, high global strategy for chronic obstructive lung disease (GOLD), and high fractional exhaled nitric oxide was significantly higher in the immediate withdrawal group than in the sequential withdrawal group (P < 0.05). In addition, according to receiver operating characteristic (ROC) curve analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly higher in patients with age > 63.5 years or GOLD > 3 in the immediate withdrawal group than in the sequential withdrawal group, suggesting that the short-term efficacy was poor.

Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province.

BACKGROUND: The 2019 novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. METHODS: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. RESULTS: None of the 137 patients (61 males, 76 females, aged 20-83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. CONCLUSIONS: The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.

The Screening Value Of ESS, SACS, BQ, And SBQ On Obstructive Sleep Apnea In Patients With Chronic Obstructive Pulmonary Disease.

Objective: To compare the performance of Epworth sleepiness scale (ESS), sleep apnea clinical score (SACS), Berlin questionnaire (BQ), and STOP-BANG questionnaire (SBQ) in screening for obstructive sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 431 patients were analyzed. All subjects completed lung function test, ESS, SACS, BQ, and SBQ survey and overnight polysomnography (PSG). According to lung function and PSG results, participants were divided into COPD with OSA group (OVS, AHI ≥5) and without OSA group (AHI <5). The value of ESS, SACS, BQ, and SBQ was compared in predicting OSA in patients with COPD by receiver-operating characteristic (ROC) curve statistics. Results: Of the 431 subjects, there were 96 cases in COPD without OSA group, and 335 cases in OVS group including 183, 96, and 56 cases of COPD combined with mild, moderate or severe OSA. In predicting different degrees of severity of OSA in patients with COPD, the value of ESS was poor with all the values of area under the curve (AUC) < 0.7. SACS and BQ had moderate predictive value in screening for severe OSA with the value of AUC of 0.750, 0.735 respectively. However, the SBQ performed best in predicting various degrees of OSA. For screening mild OSA (AHI ≥5), the ROC statistics recommended the cut-off score of SBQ >2 was considered high risk of OSA; the sensitivity, specificity, and AUC were 92.8%, 40.6%, and 0.723 respectively, the odds ratio (OR) was 2.161. When AHI ≥15, AUC for SBQ was 0.737. In predicting severe OSA (AHI ≥30), the ROC curve showed cut-off point, sensitivity, specificity, and AUC for SBQ was >4, 66.1%, 82.1%, and 0.824 respectively; the positive and negative likelihood ratio was 3.70, 0.41 separately, the OR was 2.977. Conclusion: SBQ performed better than ESS, SACS, and BQ in predicting OSA in patients with COPD.

A synergistic vascular effect of airborne particulate matter and nickel in a mouse model.

Both epidemiological and empirical studies have indicated that nickel (Ni) may play an important role in PM2.5 exposure-induced adverse cardiovascular effects. However, the underlying mechanism remains unclear. In the present study, we exposed mice to concentrated ambient PM2.5 (CAP), Ni, or coexposure to both CAP + Ni in a specially designed whole-body exposure system for a duration of 3 months and investigated their effects on vascular function, oxidative stress, and vascular inflammation. CAP + Ni exposure induced greater endothelial dysfunction compared with CAP or Ni alone. Ni exposure decreased endothelial nitric oxide synthase (eNOS) dimers in the aorta, which was potentiated by coexposure with CAP. CAP alone did not reduce NOS dimers but was more effective than Ni in decreasing phosphorylation of eNOS (S1177) and Akt (T308). Ni had minimal effects on the expression of vascular inflammatory genes but synergized with CAP in marked upregulation of tumor necrosis factor-alpha and monocyte chemotactic protein-1. The effects of Ni on NOS monomer formation in endothelial cells were redox dependent as evidenced by attenuation of effects by Tiron in cultured endothelial cells. Ni synergized with lipopolysaccharide, another bioactive component of CAP in reducing eNOS dimerization in cultured endothelial cells. Ni exposure induces endothelial dysfunction through oxidative stress-dependent inhibition of eNOS dimerization. Its interaction with other components of CAP may significantly contribute to the adverse cardiovascular effects of CAP exposure.

Effect of particulate and gaseous pollutants on spontaneous arrhythmias in aged rats.

Epidemiology studies suggest that exposure to air pollution increases the frequency of cardiac arrhythmias. A limitation of these studies is that it is difficult to link an increased risk of arrhythmias to a specific air pollutant. Animal exposure studies offer the opportunity to examine the effects of concentrated ambient fine particulate matter (PM), ultrafine PM, and copollutant gases separately. Male Fischer 344 rats, aged 18 mo, with implanted electrocardiograph (ECG) transmitters were used to determine the effects of PM on the frequency of arrhythmias. We found that old F344 rats had many spontaneous arrhythmias. An arrhythmia classification system was developed to quantify arrhythmia frequency. Arrhythmias were broadly grouped into two categories: premature beats and delayed beats. The rats were exposed to concentrated ambient PM (CAPS) or air for 4 h. The rats were exposed twice with a crossover design so each rat could serve as its own control. The CAPS concentrations were 160 microg/m(3) and 200 microg/m(3) for the first and second exposures, respectively. There was a significant increase in the frequency of irregular and delayed beats after exposure to CAPS. The same rats were subsequently exposed to laboratory-generated ultrafine carbon particles, to SO(2), or to air with a repeated crossover design. In these experiments there was no significant change in the frequency of any category of spontaneous arrhythmia following exposure to ultrafine carbon or SO(2). Thus, this study adds supporting evidence that acute exposure to elevated levels of ambient PM increases the frequency of cardiac arrhythmias.