RespirAnalyzer: an R package for analyzing data from continuous monitoring of respiratory signals.

Motivation: The analysis of data obtained from continuous monitoring of respiratory signals (CMRS) holds significant importance in improving patient care, optimizing sports performance, and advancing scientific understanding in the field of respiratory health. Results: The R package RespirAnalyzer provides an analytic tool specifically for feature extraction, fractal and complexity analysis for CMRS data. The package covers a wide and comprehensive range of data analysis methods including obtaining inter-breath intervals (IBI) series, plotting time series, obtaining summary statistics of IBI series, conducting power spectral density, multifractal detrended fluctuation analysis (MFDFA) and multiscale sample entropy analysis, fitting the MFDFA results with the extended binomial multifractal model, displaying results using various plots, etc. This package has been developed from our work in directly analyzing CMRS data and is anticipated to assist fellow researchers in computing the related features of their CMRS data, enabling them to delve into the clinical significance inherent in these features. Availability and implementation: The package for Windows is available from both Comprehensive R Archive Network (CRAN): https://cran.r-project.org/web/packages/RespirAnalyzer/index.html and GitHub: https://github.com/dongxinzheng/RespirAnalyzer.

MIRS: An AI scoring system for predicting the prognosis and therapy of breast cancer.

Tumor-infiltrating immune cells (TIICs) and metastasis are crucial characteristics for tumorigenesis. However, the potential role of their combination in breast cancer (BRCA) remains elusive. Herein, on the basis of quantifying TIICs and tumor metastasis together, we established a precise prognostic scoring system named metastatic and immunogenomic risk score (MIRS) using a neural network model. MIRS showed better performance when compared with other published signatures. MIRS stratifies patients into a high risk subtype (MIRShigh) and a low risk subtype (MIRSlow). The MIRShigh patients exhibit significantly lower survival rate compared with MIRSlow patients (P<0.0001), higher response to chemotherapy, but lower response to immunotherapy. Conversely, higher infiltration level of TIICs and significantly prolonged survival (P=0.029) are observed in MIRSlow patients, indicating sensitive response in immunotherapy. This work presents a promising indicator to guide treatment options of the BRCA population and provides a predicted webtool that is almost universally applicable to BRCA patients.

Comprehensive Analysis of Tumor Microenvironment Reveals Prognostic ceRNA Network Related to Immune Infiltration in Sarcoma.

PURPOSE: Sarcoma is the second most common solid tumor type in children and adolescents. The high level of tumor heterogeneity as well as aggressive behavior of sarcomas brings serious difficulties to developing effective therapeutic strategies for clinical application. Therefore, it is of great importance to identify accurate biomarkers for early detection and prognostic prediction of sarcomas. EXPERIMENTAL DESIGN: In this study, we characterized three subtypes of sarcomas based on tumor immune infiltration levels (TIIL), and constructed a prognosis-related competing endogenous RNA (ceRNA) network to investigate molecular regulations in the sarcoma tumor microenvironment (TME). We further built a subnetwork consisting of mRNAs and lncRNAs that are targets of key miRNAs and strongly correlated with each other in the ceRNA network. After validation using public data and experiments in vivo and in vitro, we deeply dug the biological role of the miRNAs and lncRNAs in a subnetwork and their impact on TME. RESULTS: Altogether, 5 miRNAs (hsa-mir-125b-2, hsa-mir-135a-1, hsa-mir92a-2, hsa-mir-181a-2, and hsa-mir-214), 3 lncRNAs (LINC00641, LINC01146, and LINC00892), and 10 mRNAs (AGO2, CXCL10, CD86, CASP1, IKZF1, CD27, CD247, CD69, CCR2, and CSF2RB) in the subnetwork were identified as vital regulators to shape the TME. On the basis of the systematic network, we identified that trichostatin A, a pan-HDAC inhibitor, could potentially regulate the TME of sarcoma, thereby inhibiting the tumor growth. CONCLUSIONS: Our study identifies a ceRNA network as a promising biomarker for sarcoma. This system provides a more comprehensive understanding and a novel perspective of how ceRNAs are involved in shaping sarcoma TME.

Metabolic Pathway Pairwise-Based Signature as a Potential Non-Invasive Diagnostic Marker in Alzheimer's Disease Patients.

Alzheimer's disease (AD) is an incurable neurodegenerative disorder. Early screening, particularly in blood plasma, has been demonstrated as a promising approach to the diagnosis and prevention of AD. In addition, metabolic dysfunction has been demonstrated to be closely related to AD, which might be reflected in the whole blood transcriptome. Hence, we hypothesized that the establishment of a diagnostic model based on the metabolic signatures of blood is a workable strategy. To that end, we initially constructed metabolic pathway pairwise (MPP) signatures to characterize the interplay among metabolic pathways. Then, a series of bioinformatic methodologies, e.g., differential expression analysis, functional enrichment analysis, network analysis, etc., were used to investigate the molecular mechanism behind AD. Moreover, an unsupervised clustering analysis based on the MPP signature profile via the Non-Negative Matrix Factorization (NMF) algorithm was utilized to stratify AD patients. Finally, aimed at distinguishing AD patients from non-AD groups, a metabolic pathway-pairwise scoring system (MPPSS) was established using multi-machine learning methods. As a result, many metabolic pathways correlated to AD were disclosed, including oxidative phosphorylation, fatty acid biosynthesis, etc. NMF clustering analysis divided AD patients into two subgroups (S1 and S2), which exhibit distinct activities of metabolism and immunity. Typically, oxidative phosphorylation in S2 exhibits a lower activity than that in S1 and non-AD group, suggesting the patients in S2 might possess a more compromised brain metabolism. Additionally, immune infiltration analysis showed that the patients in S2 might have phenomena of immune suppression compared with S1 and the non-AD group. These findings indicated that S2 probably has a more severe progression of AD. Finally, MPPSS could achieve an AUC of 0.73 (95%CI: 0.70, 0.77) in the training dataset, 0.71 (95%CI: 0.65, 0.77) in the testing dataset, and an AUC of 0.99 (95%CI: 0.96, 1.00) in one external validation dataset. Overall, our study successfully established a novel metabolism-based scoring system for AD diagnosis using the blood transcriptome and provided new insight into the molecular mechanism of metabolic dysfunction implicated in AD.

Public Health Measures and the Control of COVID-19 in China.

In December 2019, the COVID-19 pandemic quickly spread throughout China and beyond, posing enormous global challenges. With prompt, vigorous, and coordinated control measures, mainland China contained the spread of the epidemic within two months and halted the epidemic in three months. Aggressive containment strategy, hierarchical management, rational reallocation of resources, efficient contact tracing, and voluntary cooperation of Chinese citizens contributed to the rapid and efficient control of the epidemic, thus promoting the rapid recovery of the Chinese economy. This review summarizes China's prevention and control strategies and other public health measures, which may provide a reference for the epidemic control in other countries.

T cells dominate peripheral inflammation in a cross-sectional analysis of obesity-associated diabetes.

OBJECTIVE: Myeloid cells dominate metabolic disease-associated inflammation (metaflammation) in mouse obesity, but the contributions of myeloid cells to the peripheral inflammation that fuels sequelae of human obesity are untested. This study used unbiased approaches to rank contributions of myeloid and T cells to peripheral inflammation in people with obesity across the spectrum of metabolic health. METHODS: Peripheral blood mononuclear cells (PBMCs) from people with obesity with or without prediabetes or type 2 diabetes were stimulated with T cell-targeting CD3/CD28 or myeloid-targeting lipopolysaccharide for 20 to 72 hours to assess cytokine production using Bio-Plex. Bioinformatic modeling ranked cytokines with respect to their predictive power for metabolic health. Intracellular tumor necrosis factor α was quantitated as a classical indicator of metaflammation. RESULTS: Cytokines increased over 72 hours following T cell-, but not myeloid-, targeted stimulation to indicate that acute myeloid inflammation may shift to T cell inflammation over time. T cells contributed more tumor necrosis factor α to peripheral inflammation regardless of metabolic status. Bioinformatic combination of cytokines from all cohorts, stimuli, and time points indicated that T cell-targeted stimulation was most important for differentiating inflammation in diabetes, consistent with previous identification of a mixed T helper type 1/T helper type 17 cytokine profile in diabetes. CONCLUSIONS: T cells dominate peripheral inflammation in obesity; therefore, targeting T cells may be an effective approach for prevention/management of metaflammation.

Major Grass Pollen Allergen Components and Cross-Reactive Carbohydrate Determinants in Mugwort-Sensitized Child Patients With Allergic Respiratory Disease in Western China.

Mugwort is a common pollen allergen in western China, and this study aimed to investigate the patterns of molecular sensitization to major grass pollen allergens (mugwort, ragweed, bermuda grass, and timothy grass) and cross-reactive carbohydrate determinants (CCD) in children who were sensitized to mugwort in western China. Serum-specific IgE (sIgE) of major allergen components and CCD were detected among 121 mugwort SPT-positive children via the EUROBlotMaster system if the mugwort-sIgE was positive (MSP). A CCD inhibition test was further performed on the serum of patients with positive CCD-sIgE. Latent class analysis was used to identify the patterns of potential sensitization to major grass pollen allergens. Of a total of 100 patients with mugwort-sIgE positive (MSP), 52.0, 41.0, and 31.0% of them were positive to Art v 1, Art v 3, and Art v 4, respectively. An optimal model with three latent classes was determined using grass pollen allergens, components, and CCD. The sensitization patterns can be summarized as (1) MSP and cosensitized to ragweed, bermuda grass, and timothy grass (23.74%); (2) MSP and cosensitized to Art v 1 (54.08%); (3) MSP and cosensitized to Art v 4, Cyn d 12, Phl p 12 (22.18%). Additionally, CCD sIgE levels had a significant positive correlation with ragweed, bermuda grass, and timothy grass (P < 0.05), and CCD-Inhibitor can highly inhibit the above allergens sIgE. Our findings suggest that Art v 4 was the typical cross-reaction component of mugwort, which is cosensitized to Phl p 12 and Cyn d 12. A wide cross-reaction among ragweed, bermuda grass, and timothy grass caused by CCD was observed.

Profiles of sensitization and comorbidity in asthma patients with markedly increased serum total IgE (>1000kU/L).

Background: Immunoglobulin E (IgE) plays an important role in asthma, but a few patients exhibit extremely high levels of serum total IgE. Objective: This study aimed to investigate the profiles of comorbidity and/or complications, severity, and sensitizations in patients with asthma and with a total IgE level > 1000 kU/L. Methods: We retrospectively analyzed 170 patients with asthma and with total IgE levels of >1000 kU/L from the inpatient data base. Available information, including age, gender, body mass index, diagnosis, results of routine blood tests, pulmonary function, fractional exhaled nitric oxide, induced sputum (if any), IgE (both total and specific) tests and medication records were analyzed. Results: In the study subjects, >80% were adults, and the average total IgE level was median (interquartile range) 1438 kU/L (1181-2255 kU/L). Approximately 15% of the subjects had at least one comorbidity and/or complication, and 78.82% of the subjects were positive for at least one allergen. Airway infections (44.71%) and rhinosinusitis (41.18%) accounted for the two most common conditions despite age groups. Total IgE levels did not differ among the subjects with different conditions. Overall, mites had the highest positive rate (59.4%). Serum total IgE levels were positively correlated with house-dust mite specific IgE (sIgE) levels (r = 0.23; p < 0.05), peripheral blood eosinophil counts (r = 0.21; p < 0.01), and the number of confirmed sIgE positivity (r = 0.19; p < 0.01), and optimal scaling analysis showed that asthma severity was associated with Aspergillus fumigatus sIgE levels. Conclusion: In the subjects with asthma and with a total IgE level of >1000 kU/L, the two most common conditions were airway infections and rhinosinusitis, despite sensitization. A. fumigatus sIgE levels were closely associated with total IgE levels and asthma severity.

Clinical utility of heparin-binding protein as an acute-phase inflammatory marker in interstitial lung disease.

The role of heparin-binding protein (HBP) as an acute inflammatory marker in acute exacerbations of interstitial lung disease (AE-ILD) and some stable ILD patients is not well-established. The significance of increasing HBP during an AE-ILD is examined and the first attempt to incorporate HBP into the ILD evaluation system is made. Then, the benefit of HBP in AE-ILD was investigated. ILD patients (n = 108) were divided into subgroups based on the phase and severity of the disease. Linear trends of HBP across subgroups were observed, and correlations with common inflammatory markers were examined. Further, the HBP detection was adopted between serum and bronchoalveolar lavage fluid (BALF). Imaging and pathology changes were evaluated using various scoring criteria and compared to HBP. The relationship between HBP with ventilation, fibrosis progression, and changes in arterial oxygen levels and inflammatory markers were investigated to understand the mechanistic pathways. HBP was significantly higher in patients with AE-ILD at the early stage, compared to patients with ILD at the stable phase and its increase was both found in the serum and BALF. With the remission of the disease, there was a linear trend of progressive decline. HBP identified ILD patients who had co-infections. HBP levels increased earlier than CRP, PCT, and SAA. HBP was associated with pulmonary levels of ventilation and lesions by radiology examination, and its levels were significantly worse in AE-ILD patients. However, HBP did not show a correlation to the pathology quantitative evaluation. In conclusion, HBP could potentially evaluate the progression and prognosis of AE-ILD. Because ILD patients are susceptible to infection, and since HBP can identify co-infection, this marker would be of great clinical importance. HBP is possibly predictive of acute exacerbation.

Integrative omics analysis identifies biomarkers of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by chronic progressive pulmonary fibrosis and a poor prognosis. Genetic studies, including transcriptomic and proteomics, have provided new insight into revealing mechanisms of IPF. Herein we provided a novel strategy to identify biomarkers by integrative analysis of transcriptomic and proteomic profiles of IPF patients. We examined the landscape of IPF patients' gene expression in the transcription and translation phases and investigated the expression and functions of two new potential biomarkers. Differentially expressed (DE) mRNAs were mainly enriched in pathways associated with immune system activities and inflammatory responses, while DE proteins are related to extracellular matrix production and wound repair. The upregulated genes in both phases are associated with wound repair and cell differentiation, while the downregulated genes in both phases are associated with reduced immune activities and the damage of the alveolar tissues. On this basis, we identified thirteen potential marker genes. Among them, we validated the expression changes of butyrophilin-like 9 (BTNL9) and plasmolipin (PLLP) and investigated their functional pathways in the IPF mechanism. Both genes are downregulated in the tissues of IPF patients and Bleomycin-induced mice, and co-expression analysis indicates that they have a protective effect by inhibiting extracellular matrix production and promoting wound repair in alveolar epithelial cells.

Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing.

Background: BRCA1 plays critical roles in mammary gland development and mammary tumorigenesis. And loss of BRCA1 induces mammary tumors in a stochastic manner. These tumors present great heterogeneity at both intertumor and intratumor levels. Methods: To comprehensively elucidate the heterogeneity of BRCA1 deficient mammary tumors and the underlying mechanisms for tumor initiation and progression, we conducted bulk and single cell RNA sequencing (scRNA-seq) on both mammary gland cells and mammary tumor cells isolated from Brca1 knockout mice. Results: We found the BRCA1 deficient tumors could be classified into four subtypes with distinct molecular features and different sensitivities to anti-cancer drugs at the intertumor level. Whereas within the tumors, heterogeneous subgroups were classified mainly due to the different activities of cell proliferation, DNA damage response/repair and epithelial-to-mesenchymal transition (EMT). Besides, we reconstructed the BRCA1 related mammary tumorigenesis to uncover the transcriptomes alterations during this process via pseudo-temporal analysis of the scRNA-seq data. Furthermore, from candidate markers for BRCA1 mutant tumors, we discovered and validated one oncogene Mrc2, whose loss could reduce mammary tumor growth in vitro and in vivo. Conclusion: Our study provides a useful resource for better understanding of mammary tumorigenesis induced by BRCA1 deficiency.

Increase in Indoor Inhalant Allergen Sensitivity During the COVID-19 Pandemic in South China: A Cross-Sectional Study from 2017 to 2020.

PURPOSE: Public health measures during COVID-19 have led to an unprecedented change in social lifestyle which might have an impact on the allergen sensitization in population. We sought to explore the prevalence patterns of serum inhalant and food allergen-specific IgE (sIgE) sensitization and serum total immunoglobulin E (tIgE) level among patients with clinical symptoms of suspected allergic diseases before and during the COVID-19 pandemic in south China. PATIENTS AND METHODS: A large epidemiology study was conducted on the prevalence patterns of sIgE sensitization and serum tIgE level among 13,715 patients with allergic symptoms in south China from 2017 to 2020. Chi-square test and Fisher exact test were used to test statistical significance of allergen sensitization difference among years. Logistic regression was performed to assess the magnitudes of the differences among years by adjusted odds ratios and 95% confidence intervals. RESULTS: The number of hospital visits for patients with suspected allergy symptoms decreased during COVID-19. The positive rates of indoor inhalant allergens (house dust mites, German cockroach, dog dander) and tIgE increased significantly in 2020, while no significant differences were found in food allergens (egg white, milk, soya bean, shrimp) before and during the COVID-19 pandemic. The odds of sIgE positives in indoor inhalant allergens and tIgE positive for 2017 and 2020 were all larger than 1.00. After grouping by age and gender, there were significant differences in the positive rates of indoor inhalant allergens and tIgE when comparing 2020 with 2017. CONCLUSION: The prevalence of sensitization increased significantly to indoor inhalant allergens but not to food allergens in south China during the COVID-19 pandemic.

Factors Affecting the Antibody Immunogenicity of Vaccines against SARS-CoV-2: A Focused Review.

Vaccines are a crucial part of the global anti-pandemic effort against COVID-19. The effects of vaccines, as well as their common influencing factors, are the most important issues that we should focus on at this time. To this end, we review statistics on immunogenicity after vaccination, using neutralizing antibodies as the main reference index. Age, infection history, and virus variants are compared, and vaccination program recommendations are made accordingly. Suggestions are made to address concerns raised by the vaccines' shortened development cycle, as well as the emergence of immunity escape of viral variants. Finally, a brief description and future prospects are provided based on the principle of the ADE effect and previous experience with similar viruses.

The Molecule Sensitized Pattern of Atopic Dermatitis Patients Who Co-Sensitized to Shrimp, Cockroaches, Crab and House Dust Mites.

This study investigated the molecule sensitized pattern of atopic dermatitis patients who co-sensitized to shrimp, cockroaches, crab and house dust mites allergens and promoted the development of clinical accurate diagnosis and treatment.

Short-term exposure to ambient air pollution and hospital visits for IgE-mediated allergy: A time-stratified case-crossover study in southern China from 2012 to 2019.

BACKGROUND: Because of the limited epidemiological evidence on the association between acute air pollutants and allergy, there is a need to investigate this association, especially between the short-term exposure to air pollution and the serum Immunoglobulin E (IgE)-mediated allergy. METHODS: A total of 39,569 IgE test results and demographic characteristics were obtained in the First Affiliated Hospital of Guangzhou Medical University between August 2012 and September 2019. Ninety-nine specific allergens were tested according to clinical diagnosis. The logistic regression was used to assess the effects of CO, NO2 and PM2.5 exposure on the risk of sensitization to specific inhalant/food allergens. Generalized additive models with multivariate adjustments were utilized to model the exposure-response relationship. Stratified analyses were performed to estimate the reliability of correlations in various subgroups. FINDINGS: Single-pollutant models indicate that the 3-day moving average (lag2-4) of CO, PM2.5 or NO2 is associated with the increased risk for allergic diseases related to specific inhaled allergens. In multi-pollutant models, the adjusted Odds Ratio (OR) 95% (Confidence Interval, CI) increases by 8% (95% CI, 2%-15%) for per increment of 0.2 mg/m3 in CO levels, and rises by 8% (95% CI, 2%-13%) for each increase of 16.3 µg/m3 in PM2.5 concentration. The associations are stronger in youngsters (<18, years) but not significantly different by gender. Particularly, a significantly stronger association between PM2.5 exposure and hospital visits for inhaled allergy is observed in patients who are exposed to lower concentration of SO2 (<10.333 µg/m3) and higher levels of NO2 (≥42.0 µg/m3), as well as patients enrolled after 2017. INTERPRETATION: The short-term exposure to CO/PM2.5 increases the number of hospital visits for IgE-mediated allergy, especially for the sensitization to specific inhalant allergens. Therefore, to prevent inhaled allergies, the public policy for controlling air pollution needs to be considered seriously. FUNDING: This study was supported by the University of Macau (grant numbers: FHS-CRDA-029-002-2017 and MYRG2018-00,071-FHS) as well as the Science and Technology Development Fund, Macau SAR (File no. 0004/2019/AFJ and 0011/2019/AKP). This work was also supported by the National Natural Science Foundation of China (81,871,736), the National Key Technology R&D Program (2018YFC1311902), the Guangdong Science and Technology Foundation (2019B030316028), the Guangzhou Municipal Health Foundation (20191A011073), and the Guangzhou Science and Technology Foundation (201,804,020,043).

Comprehensive transcriptome analysis of peripheral blood unravels key lncRNAs implicated in ABPA and asthma.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity lung disease caused by a fungus known as Aspergillus fumigatus. It complicates and aggravates asthma. Despite their potential associations, the underlying mechanisms of asthma developing into ABPA remain obscure. Here we performed an integrative transcriptome analysis based on three types of human peripheral blood, which derived from ABPA patients, asthmatic patients and health controls, aiming to identify crucial lncRNAs implicated in ABPA and asthma. Initially, a high-confidence dataset of lncRNAs was identified using a stringent filtering pipeline. A comparative mutational analysis revealed no significant difference among these samples. Differential expression analysis disclosed several immune-related mRNAs and lncRNAs differentially expressed in ABPA and asthma. For each disease, three sub-networks were established using differential network analysis. Many key lncRNAs implicated in ABPA and asthma were identified, respectively, i.e., AL139423.1-201, AC106028.4-201, HNRNPUL1-210, PUF60-218 and SREBF1-208. Our analysis indicated that these lncRNAs exhibits in the loss-of-function networks, and the expression of which were repressed in the occurrences of both diseases, implying their important roles in the immune-related processes in response to the occurrence of both diseases. Above all, our analysis proposed a new point of view to explore the relationship between ABPA and asthma, which might provide new clues to unveil the pathogenic mechanisms for both diseases.

Soluble form of suppression of tumorigenicity-2 predicts clinical stability of inpatients with community-acquired pneumonia.

The soluble form of the suppression of tumorigenicity-2 (sST2) is a biomarker for risk classification and prognosis of heart failure, and its production and secretion in the alveolar epithelium are significantly correlated with the inflammation-inducing in pulmonary diseases. However, the predictive value of sST2 in pulmonary disease had not been widely studied. This study investigated the potential value in prognosis and risk classification of sST2 in patients with community-acquired pneumonia. Clinical data of ninety-three CAP inpatients were retrieved and their sST2 and other clinical indices were studied. Cox regression models were constructed to probe the sST2's predictive value for patients' restoring clinical stability and its additive effect on pneumonia severity index and CURB-65 scores. Patients who did not reach clinical stability within the defined time (30 days from hospitalization) have had significantly higher levels of sST2 at admission (P < 0.05). In univariate and multivariate Cox regression analysis, a high sST2 level (≥72.8 ng/mL) was an independent reverse predictor of clinical stability (P < 0.05). The Cox regression model combined with sST2 and CURB-65 (AUC: 0.96) provided a more accurate risk classification than CURB-65 (AUC:0.89) alone (NRI: 1.18, IDI: 0.16, P < 0.05). The Cox regression model combined with sST2 and pneumonia severity index (AUC: 0.96) also provided a more accurate risk classification than pneumonia severity index (AUC:0.93) alone (NRI: 0.06; IDI: 0.06, P < 0.05). sST2 at admission can be used as an independent early prognostic indicator for CAP patients. Moreover, it can improve the predictive power of CURB-65 and pneumonia severity index score.

Metabolomic profiling of anaerobic and aerobic energy metabolic pathways in chronic obstructive pulmonary disease.

While there is no cure for chronic obstructive pulmonary disease (COPD), its progressive nature and the formidable challenge to manage its symptoms warrant a more extensive study of the pathogenesis and related mechanisms. A new emphasis on COPD study is the change of energy metabolism. For the first time, this study investigated the anaerobic and aerobic energy metabolic pathways in COPD using the metabolomic approach. Metabolomic analysis was used to investigate energy metabolites in 140 COPD patients. The significance of energy metabolism in COPD was comprehensively explored by the Global Initiative for Chronic Obstructive Lung Disease-GOLD grading, acute exacerbation vs. stable phase (either clinical stability or four-week stable phase), age group, smoking index, lung function, and COPD Assessment Test (CAT) score. Through comprehensive evaluation, we found that COPD patients have a significant imbalance in the aerobic and anaerobic energy metabolisms in resting state, and a high tendency of anaerobic energy supply mechanism that correlates positively with disease progression. This study highlighted the significance of anaerobic and low-efficiency energy supply pathways in lung injury and linked it to the energy-inflammation-lung ventilatory function and the motion limitation mechanism in COPD patients, which implies a novel therapeutic direction for this devastating disease.

Epidemiological Characteristics of Influenza A and B in Macau, 2010-2018.

Influenza is one of the major respiratory diseases in humans. Macau is a tourist city with high density of population and special population mobility. The study on the epidemiological characteristics of influenza in Macau should bring great value for preventing influenza in tourist cities like Macau in the world. In this study, we collected a total of 104,874 samples with influenza-like illness (ILI) in Macau from 2010 to 2018. Chi-square test and binary multivariable logistic regression were used to investigate the epidemiological characteristics of influenza A and B in Macau. Among these ILI samples, the overall positive rate is 17.17% for influenza A and 6.97% for influenza B. The epidemics of influenza in three years (i.e., 2012, 2017 and 2018) differ from the remaining years (i.e., normal years). In a normal year, influenza A occurs year-round whereas influenza B is seasonal. Our research shows significant differences in influenza infections between different age groups in normal years. Interestingly, our analysis shows no significant difference between locals and tourists in influenza A and B infection in a normal year, whereas the odds of influenza A in tourists were significantly higher than those in locals in July 2017 and the odds of influenza B in tourists were significantly higher than those in locals in January-February 2012 and January-February 2018. This is possibly attributed by the policy of free vaccination to everyone in Macau. These findings should be valuable for preventing influenza in not only Macau but also the world.

Krebs Von den Lungen-6 as a predictive indicator for the risk of secondary pulmonary fibrosis and its reversibility in COVID-19 patients.

Dysregulated immune response and abnormal repairment could cause secondary pulmonary fibrosis of varying severity in COVID-19, especially for the elders. The Krebs Von den Lungen-6 (KL-6) as a sensitive marker reflects the degree of fibrosis and this study will focus on analyzing the evaluative efficacy and predictive role of KL-6 in COVID-19 secondary pulmonary fibrosis. The study lasted more than three months and included total 289 COVID-19 patients who were divided into moderate (n=226) and severe groups (n=63) according to the severity of illness. Clinical information such as inflammation indicators, radiological results and lung function tests were collected. The time points of nucleic acid test were also recorded. Furthermore, based on Chest radiology detection, it was identified that 80 (27.7%) patients developed reversible pulmonary fibrosis and 34 (11.8%) patients developed irreversible pulmonary fibrosis. Receiver operating characteristic (ROC) curve analysis shows that KL-6 could diagnose the severity of COVID-19 (AUC=0.862) and predict the occurrence of pulmonary fibrosis (AUC = 0.741) and irreversible pulmonary fibrosis (AUC=0.872). Importantly, the cross-correlation analysis demonstrates that KL-6 rises earlier than the development of lung radiology fibrosis, thus also illuminating the predictive function of KL-6. We set specific values (505U/mL and 674U/mL) for KL-6 in order to assess the risk of pulmonary fibrosis after SARS-CoV-2 infection. The survival curves for days in hospital show that the higher the KL-6 levels, the longer the hospital stay (P<0.0001). In conclusion, KL-6 could be used as an important predictor to evaluate the secondary pulmonary fibrosis degree for COVID-19.