Novel 15N Metabolic Labeling-Based Large-Scale Absolute Quantitative Proteomics Method for Corynebacterium glutamicum.

With fast growth, synthetic biology powers us with the capability to produce high commercial value products in an efficient resource/energy-consuming manner. Comprehensive knowledge of the protein regulatory network of a bacterial host chassis, e.g., the actual amount of the given proteins, is the key to building cell factories for certain target hyperproduction. Many talent methods have been introduced for absolute quantitative proteomics. However, for most cases, a set of reference peptides with isotopic labeling (e.g., SIL, AQUA, QconCAT) or a set of reference proteins (e.g., commercial UPS2 kit) needs to be prepared. The higher cost hinders these methods for large sample research. In this work, we proposed a novel metabolic labeling-based absolute quantification approach (termed nMAQ). The reference Corynebacterium glutamicum strain is metabolically labeled with 15N, and a set of endogenous anchor proteins of the reference proteome is quantified by chemically synthesized light (14N) peptides. The prequantified reference proteome was then utilized as an internal standard (IS) and spiked into the target (14N) samples. SWATH-MS analysis is performed to obtain the absolute expression levels of the proteins from the target cells. The cost for nMAQ is estimated to be less than 10 dollars per sample. We have benchmarked the quantitative performance of the novel method. We believe this method will help with the deep understanding of the intrinsic regulatory mechanism of C. glutamicum during bioengineering and will promote the process of building cell factories for synthetic biology.

Early detection of COPD based on graph convolutional network and small and weakly labeled data.

Chronic obstructive pulmonary disease (COPD) is a common disease with high morbidity and mortality, where early detection benefits the population. However, the early diagnosis rate of COPD is low due to the absence or slight early symptoms. In this paper, a novel method based on graph convolution network (GCN) for early detection of COPD is proposed, which uses small and weakly labeled chest computed tomography image data from the publicly available Danish Lung Cancer Screening Trial database. The key idea is to construct a graph using regions of interest randomly selected from the segmented lung parenchyma and then input it into the GCN model for COPD detection. In this way, the model can not only extract the feature information of each region of interest but also the topological structure information between regions of interest, that is, graph structure information. The proposed GCN model achieves an acceptable performance with an accuracy of 0.77 and an area under a curve of 0.81, which is higher than the previous studies on the same dataset. GCN model also outperforms several state-of-the-art methods trained at the same time. As far as we know, it is also the first time using the GCN model on this dataset for COPD detection.

A Novel CT-Based Radiomics Features Analysis for Identification and Severity Staging of COPD.

RATIONALE AND OBJECTIVES: To evaluate the role of radiomics based on Chest Computed Tomography (CT) in the identification and severity staging of chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: This retrospective analysis included 322 participants (249 COPD patients and 73 control subjects). In total, 1395 chest CT-based radiomics features were extracted from each participant's CT images. Three feature selection methods, including variance threshold, Select K Best method, and least absolute shrinkage and selection operator (LASSO), and two classification methods, including support vector machine (SVM) and logistic regression (LR), were used as identification and severity classification of COPD. Performance was compared by AUC, accuracy, sensitivity, specificity, precision, and F1-score. RESULTS: 38 and 10 features were selected to construct radiomics models to detect and stage COPD, respectively. For COPD identification, SVM classifier achieved AUCs of 0.992 and 0.970, while LR classifier achieved AUCs of 0.993 and 0.972 in the training set and test set, respectively. For the severity staging of COPD, the mentioned two machine learning classifiers can better differentiate less severity (GOLD1 + GOLD2) group from greater severity (GOLD3 + GOLD4) group. The AUCs of SVM and LR is 0.907 and 0.903 in the training set, and that of 0.799 and 0.797 in the test set. CONCLUSION: The present study showed that the novel radiomics approach based on chest CT images that can be used for COPD identification and severity classification, and the constructed radiomics model demonstrated acceptable performance.

Efficacy and safety of aerosol inhalation of recombinant human interferon α1b (IFNα1b) injection for noninfluenza viral pneumonia, a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: To investigate the efficacy and safety of aerosol inhalation of recombinant human interferon α1b (IFNα1b) injection for noninfluenza viral pneumonia. METHODS: One hundred sixty-four patients with noninfluenza viral pneumonia were divided into IFNα1b and control groups. The IFNα1b group received routine treatment + aerosol inhalation of recombinant human IFNα1b injection (50 µg × 2 injections, bid). The control group received routine treatment + IFN analog (two injections, bid). Overall response rate (ORR) of five kinds clinical symptoms. Further outcomes were daily average score and the response rate of each of the symptoms above. RESULTS: A total of 163 patients were included in the full analysis set (FAS) and 151 patients were included in the per-protocol set (PPS). After 7 days of treatment, ORR of clinical symptoms was higher in IFNα1b group than that in control group for both the FAS and PPS. Moreover, after 7 days of treatment, the daily score of three efficacy indexes including expectoration, respiratory rate, and pulmonary rales were improved. The ORRs for expectoration and pulmonary rales were higher in the IFNα1b group than in the control group (P < 0.05). There were no significant differences of the ORRs for coughing, chest pain and respiratory rate between the two groups (P > 0.05). The incidence of adverse events was 6.5% (n = 5) in IFNα1b group and 3.5% (n = 3) in control group (P > 0.05). CONCLUSION: Aerosol inhalation of recombinant human IFNα1b is safe and it can improve the clinical symptoms of noninfluenza viral pneumonia.

Anxiety and depression in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Results from a Chinese survey.

Limited studies have focused on mental symptoms (anxiety and depression) and their impact on quality of life (QoL) in patients with pulmonary hypertension (PH). The objective of the present study was to assess the prevalence of anxiety and depression and their association with QoL in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH) in a Chinese population. Patients diagnosed with PH by right heart catheterization between March 2015 and February 2016 were recruited. QoL [short form 36 Health Survey Questionnaire (SF-36)] and depression (Patient Health Questionnaire depression scale-9) and anxiety (Generalized Anxiety Disorder-7) were assessed at baseline. Patients were followed up every 3 months. A total of 36 patients with PAH and 62 patients with CTEPH were enrolled. According to the results of the clinical examination and the questionnaires for depression and anxiety, patients were divided into two groups: Group 1, with depression and/or anxiety (n=65, 66.3%) and group 2, without depression or anxiety (n=33, 33.7%). At baseline, the two groups did not differ in their hemodynamics. Patients with depression and/or anxiety (group 1) had a significantly lower score in all subscales of SF-36 (P<0.05). The impairment of QoL significantly correlated with the severity of depression (P<0.001) and anxiety (P<0.05). During the follow-up period, end-point events (death or admission due to deterioration) occurred in 17 patients (17.3%); 8 patients (8.1%) were lost to follow-up. The end-point event-free survival rate in group 2 was significantly higher than that in group 1. Multivariate logistic regression analysis suggested that the financial situation and right ventricular enlargement were influencing factors of depression and/or anxiety. In conclusion, in patients with PH from a Chinese population, anxiety and depression were frequently encountered and significantly correlated with QoL. The significant relevant factors influencing anxiety/depression were the financial situation and right ventricular enlargement and patients with depression had a worse prognosis than those without.

Disease severity and clinical outcomes of community-acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicentre prospective registry study from the CAP-China Network.

Although broad knowledge of influenza viral pneumonia has been established, the significance of non-influenza respiratory viruses in community-acquired pneumonia (CAP) and their impact on clinical outcomes remains unclear, especially in the non-immunocompromised adult population.Hospitalised immunocompetent patients with CAP were prospectively recruited from 34 hospitals in mainland China. Respiratory viruses were detected by molecular methods. Comparisons were conducted between influenza and non-influenza viral infection groups.In total, 915 out of 2336 adult patients with viral infection were enrolled in the analysis, with influenza virus (28.4%) the most frequently detected virus, followed by respiratory syncytial virus (3.6%), adenovirus (3.3%), human coronavirus (3.0%), parainfluenza virus (2.2%), human rhinovirus (1.8%) and human metapneumovirus (1.5%). Non-influenza viral infections accounted for 27.4% of viral pneumonia. Consolidation was more frequently observed in patients with adenovirus infection. The occurrence of complications such as sepsis (40.1% versus 39.6%; p=0.890) and hypoxaemia (40.1% versus 37.2%; p=0.449) during hospitalisation in the influenza viral infection group did not differ from that of the non-influenza viral infection group. Compared with influenza virus infection, the multivariable adjusted odds ratios of CURB-65 (confusion, urea >7 mmol·L-1, respiratory rate ≥30 breaths·min-1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) ≥3, arterial oxygen tension/inspiratory oxygen fraction <200 mmHg, and occurrence of sepsis and hypoxaemia for non-influenza respiratory virus infection were 0.87 (95% CI 0.26-2.84), 0.72 (95% CI 0.26-1.98), 1.00 (95% CI 0.63-1.58) and 1.05 (95% CI 0.66-1.65), respectively. The hazard ratio of 90-day mortality was 0.51 (95% CI 0.13-1.91).The high incidence of complications in non-influenza viral pneumonia and similar impact of non-influenza respiratory viruses relative to influenza virus on disease severity and outcomes suggest more attention should be given to CAP caused by non-influenza respiratory viruses.

[Proportion and prevention of venous thromboembolism among hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease in Beijing].

OBJECTIVE: To explore the proportion and prevention status of venous thromboembolism (VTE) among hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing. METHODS: Based on a multi-center retrospective study, a total of 636 hospitalized AECOPD patients from 17 class 2/3 hospitals in Beijing were examined from September 1, 2011 to March 31, 2012. They fulfilled one of the following criteria: respiratory failure type II, on invasive or non-invasive mechanical ventilation, hospitalization for pulmonary infection, bedridden duration ≥ 3 days and congestive heart failure. All investigators received standardized training and used a standardized questionnaire to collect data on VTE risk factors, the diagnosis of VTE and the utilization of VTE prophylaxis. According to Caprini score, they were categorized into 3 groups of lower risk (Caprini score ≤ 3), moderate risk (Caprini score 4-6) and high risk ( ≥ 7) to compare the intergroup differences in the VTE proportion and the utilization of VTE prophylaxis. RESULTS: A total of 636 patients were assessed. There were 416 males and 220 females with a mean (SD) age of 74.9 ± 9.3 years. Among them, 133 patients received lower extremity venous ultrasonic examination and 92 were diagnosed with deep venous thrombosis (DVT) including 2 patients with pulmonary thromboembolism (PTE). Thus the overall incidence of VTE was 14.5% (92/636) and increased with age (Ptrend = 0.044). The proportion of VTE in asymptomatic patients was higher in those symptomatic ones (21.1% vs 8.0%, P = 0.000). And it was the highest in high risk group, followed by lower risk and moderate risk groups at 17.9% (14/78), 16.0% (26/163) and 13.2% (52/395) respectively, There was no statistical significance (P = 0.450 for group difference, Ptrend = 0.946). Among 544 patients without VTE, only 19.1% (104/544) employed the pharmacologic and/or mechanical methods for preventing VTE. The prevention proportion gradually increased with rising Caprini score, i.e. 17.5%, 18.4% and 26.6% for lower, moderate and higher risk group respectively. There was no statistical significance (P = 0.266 for group difference, Ptrend = 0.201). CONCLUSIONS: The proportion of VTE is relatively higher. However, the preventive methods are significantly underutilized among hospitalized AECOPD patients in Beijing.