Analysis of the total serum IgE levels in patients with acute exacerbations chronic obstructive pulmonary disease: A retrospective study.

Currently, few studies have demonstrated the relationship between total serum IgE (T-IgE) and acute exacerbation chronic obstructive pulmonary disease (AECOPD). In this study, T-IgE in AECOPD patients were investigated and jointly analyzed with the clinical characteristics. AECOPD patients hospitalized from July 2018 to July 2019 were included in this study. In this patient cohort, clinical information was investigated. Routine blood tests, C-reactive protein and T-IgE levels of patients were determined along with blood gas analysis. The length of hospital stays, mechanical ventilation during hospitalization, ICU admission, glucocorticoid related clinical information were recorded. A total of 285 AECOPD patients were included in this study, which consisted of a high proportion of males. Of all patients, 49.82% patients exhibited higher T-IgE levels. Based on the reference T-IgE value 60 kU/L, patients were divided into high T-IgE group with T-IgE > 60 kU/L, and low T-IgE group with T-IgE ≤ 60 kU/L. There was no significant difference in the dosage of glucocorticoid between the two groups. Patients in the high T-IgE group had shorter hospital stays and lower probability of mechanical ventilation compared to the low T-IgE group. After adjustment for confounding factors, T-IgE was negatively correlated with the length of hospital stays. AECOPD patients with elevated T-IgE had shorter hospital stays and lower risks of mechanical ventilation and ICU admission. Our results showed that T-IgE might play an important role on evaluating the condition and guiding for treatment decisions in AECOPD patients.

ceRNA Network Analysis Reveals Potential Key miRNAs and Target Genes in COVID-19-Related Chronic Obstructive Pulmonary Disease.

The continued spread of SARS-CoV-2 has presented unprecedented obstacles to the worldwide public health system. Especially, individuals with chronic obstructive pulmonary disease (COPD) are at a heightened risk of contracting SARS-CoV-2 infection due to their pre-existing respiratory symptoms that are not well-managed. However, the viral mechanism of affecting the expression of host genes, COPD progression, and prognosis is not clear yet.This study integrated the differential expression information of COPD patients and then calculated the correlation between mRNAs and miRNAs to construct a COPD-specific ceRNA network. The DEGs of individuals with SARS-CoV-2 infection and anticipated miRNAs and their targets were analyzed in 9 SARS-CoV-2 sequences from different geographic locations. Furthermore, combining the experimentally validated miRNAs and genes, the regulatory miRNA-mRNA relationships were identified. All the regulatory relationships were integrated into the COPD-specific network and the network modules were explored to get insight into the functional mechanism of SARS-CoV-2 infection in COPD patients.A higher proportion of DEGs compete with the same miRNA suggesting a higher expression of genes in the COPD-specific ceRNA network. Hsa-miR-21-3p is the largest connected point in the network, but the proportion of genes upregulated by hsa-miR-21-3p is low (P = 0.1406). This indicates that the regulatory relationship of competitive inhibition has little effect on has-miR-21, and the high expression pattern is a poor prognostic factor in COPD. Hsa-miR-15a-5p is the most significant miRNA with the highest proportion of DEGs. And ANXA2P3 is the only gene in the COPD ceRNA network that interferes with hsa-miR-15a-5p. In addition, we found that has-miR-1184- and has-miR-99-cored modules were significant, and genes ZDHHC18, PCGF3, and KIAA0319L interacting with them were all associated with COPD prognosis, and high expression of these genes could lead to poor prognosis in COPD.The key regulators such as miR-21, miR-15a, ANXA2P3, ZDHHC18, PCGF3, and KIAA0319L can be used as prognostic biomarkers for early intervention in COPD with SARS-CoV-2 infection.

Value of the neutrophil-to-lymphocyte ratio in chronic obstructive pulmonary disease complicated with pulmonary hypertension.

OBJECTIVE: To investigate the relationship between the neutrophil-to-lymphocyte ratio and chronic obstructive pulmonary disease complicated with pulmonary hypertension (COPD + PH). METHODS: We retrospectively analyzed clinical data from 242 COPD patients at our hospital from July 2018 to July 2019. Patients underwent examinations including blood analysis, C-reactive protein, N-terminal brain natriuretic peptide (BNP), pulmonary function, and cardiac color ultrasound. RESULTS: Patients were divided into the COPD and COPD + PH groups using pulmonary arterial pressure (<50 and ≥50 mmHg, respectively). Compared with the COPD group, the COPD + PH group had greater pulmonary arterial pressure, smoking history, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, BNP, Chronic Obstructive Pulmonary Disease Assessment Test score, and right atrium and ventricular diameters, but smaller body mass index, forced vital capacity, lymphocyte count, and left ventricular diameter. BNP and NLR had positive effects on PH; forced vital capacity had a negative impact. Moreover, BNP (area under the curve [AUC] = 0.748, sensitivity = 0.692, specificity = 0.701) and NLR (AUC = 0.679, sensitivity = 0.831, specificity = 0.452) had predictive value for PH, and both were positively correlated with PH. CONCLUSIONS: NLR is associated with COPD + PH, and may be useful for its diagnosis.

The correlational study about neutrophil-to-lymphocyte ratio and exercise tolerance of chronic obstructive pulmonary disease patients.

To study the relationship between neutrophil to lymphocyte ratio (NLR) and exercise tolerance of patients with chronic obstructive pulmonary disease (COPD).235 patients with COPD were selected as the study subjects. Complete blood count, C reactive protein (CRP), pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council, the COPD assessment test, and clinical COPD questionnaire were tested. Heart rate, oxygen saturation, and Borg scale were tested before or after 6MWD test.By the median of NLR, the subjects were divided into 2 groups, NLR ≥4.5 group and NLR <4.5 group. The white blood cell count (WBC), CRP and deoxygenation saturation in the NLR ≥4.5 group were higher than those in the NLR <4.5 group, while the age, body mass index (BMI), 6MWD, and heart rate variation were lower than those in the NLR <4.5 group. CRP, WBC, and deoxygenation saturation had positive effects on NLR, BMI, 6MWT, and heart rate variation had negative effects on NLR. The Pearson correlation analysis showed NLR was positively correlated with WBC, CRP, BMI index, 6MWT, and deoxygenation saturation, while it was negatively correlated with BMI and heart rate variation.NLR might associate with exercise tolerance and cardiorespiratory reserve of COPD patients, and could be used as an indicator of muscle function in COPD patients.

Upregulation of microRNA-1303 is a potential prognostic marker of non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the major subtype of lung cancer, imposing a huge disease burden worldwide. MicroRNA-1303 (miR-1303) has been demonstrated to be involved in several diseases, including cancers. In this study, we aimed to investigate the role of miR-1303 in NSCLC. METHODS: We quantified the expression levels of miR-1303 in NSCLC tissues and cells using the qRT-PCR assay. Then the association between miR-1303 expression and clinical characteristics of patients was analyzed using the χ2 test. The Kaplan-Meier and multivariate Cox regression assays were used to investigate the prognostic value of miR-1303 in NSCLC. Furthermore, the functional proliferation, migration, and invasion assays were used to explore the miR-1303 functions in vitro. RESULTS: The expression of miR-1303 was upregulated in NSCLC tissue samples and cells. The upregulation of miR-1303 was associated with TNM stage and lymph node metastasis. The survival time of NSCLC patients with high expression of miR-1303 was shorter than those with low expression. The functional analyses revealed that overexpression of miR-1303 in H1299 and A549 cells promoted cell proliferation, migration, and invasion. CONCLUSION: These results suggest that miR-1303 may be a potential prognostic biomarker for NSCLC and be involved in the progression of NSCLC.

Differentially expressed lncRNAs in peripheral blood mononuclear cells from middle-aged female patients with rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: Interstitial lung disease (ILD) is frequently associated with rheumatoid arthritis (RA) and has a large impact on the prognosis of RA, particularly among females, with an increased prevalence and severity compared with that of males. Here, we aimed to investigate the lncRNA profiles in peripheral blood mononuclear cells (PBMCs) from middle-aged female patients with RA-ILD to determine whether they could help diagnose RA-ILD. METHOD: We collected PBMCs from middle-aged female healthy controls, and RA and RA-ILD patients, excluding those with known risk factors of RA-ILD, such as being elderly or male, smoking, and having a history of other diseases. Then, a microarray analysis was applied to profile the lncRNA and mRNA levels in 3 pairs of samples. qPCR was performed to evaluate the candidate lncRNAs from 20 participants of each group. RESULTS: The expression levels of NR_002819, NR_038935, and ENST00000603415 were significantly increased in the RA-ILD group, while the expression level of ENST00000560199 was significantly decreased. As risk factors for RA-ILD, the area under the curve (AUC) values of NR_002819, NR_038935, and ENST00000603415 were 0.858, 0.704 (medium diagnostic accuracy), and 0.976 (high diagnostic accuracy), respectively. As a protective factor for RA-ILD, the AUC of ENST00000560199 was 0.853(medium diagnostic accuracy). CONCLUSIONS: To the best of our knowledge, this is the first study of lncRNA profiles in RA-ILD. The expression levels of NR_002819 (MALAT1), NR_038935, ENST00000603415, and ENST00000560199 were significantly different in the RA-ILD group and could be potential biomarkers for the assessment and diagnosis of middle-aged female RA-ILD patients. Key Points • The expression profile of lncRNAs in PBMCs from RA-ILD patients was evaluated. • NR_002819, NR_038935, and ENST00000603415 increased in RA-ILD patients. •ENST00000560199 decreased in RA-ILD patients. • The 4 lncRNAs might be potential biomarkers for diagnosis of RA-ILD.

Effect of simvastatin on MMPs and TIMPs in cigarette smoke-induced rat COPD model.

BACKGROUND: Proteases may play an important role in the development of chronic obstructive pulmonary disease and emphysema in response to cigarette smoke exposure (CSE). The current study was designed to investigate the expression of matrix metalloproteinase (MMP)-8, MMP-9, MMP-12, tissue inhibitor of MMP (TIMP)-1, and TIMP-4 in rat lung tissues in response to CSE, and assessed the effect of simvastatin in regulating expression of MMPs and TIMPs. METHODS: Thirty normal Sprague Dawley (SD) rats were divided into control (n=10), CSE (n=10), and CSE plus simvastatin (n=10) groups. Animals were whole-body exposed to the cigarette smoke in the box for 1 hour each time, twice a day, 5 days a week for 16 weeks. Animals of CSE + simvastatin group were intra-gastrically administered simvastatin at a dose of 5 mg/kg/day followed by CSE. Bronchoalveolar lavage fluid was harvested for inflammatory cell count and lung tissues were stained for morphologic examination. Expression of mRNA and protein level of MMP-8, MMP-9, MMP-12, TIMP-1, and TIMP-4 was assessed by real-time reverse transcription polymerase chain reaction and immunohistochemistry, respectively. RESULTS: CSE resulted in a significant increase of mean linear intercept (MLI: 34.6±2.0 µm) and bronchial wall thickness and diameter (BWT/D, 0.250±0.062) compared to control (MLI: 24.0±1.7 µm, BWT/D: 0.160±0.034, P<0.01). In contrast, mean alveolar number was significantly decreased in the CSE group than that in the control group (13.5±2.0 of CSE vs 21.5±2.0 N/µm2 of control, P>0.01). Simvastatin slightly but not significantly prevented alteration of MLI, BWT/D, and mean alveolar number (MLI: 33.4±1.4 µm; BWT/D: 0.220±0.052; mean alveolar number: 15.5±2.5 N/µm2, P>0.05). Total white blood cell was significantly increased in the bronchoalveolar lavage fluid of smoking group (3.3±2.5×109 cells/L vs 1.1±1.3×109 cells/L of control, P<0.01), and it was significantly reduced by simvastatin (2.3±2.1×109 cells/L, P<0.01). CSE resulted in significantly increased accumulation of neutrophils and macrophages (neutrophils: 14.5%±1.3% of CSE group vs 9.1%±1.5% of control; macrophage: 91%±3% of CSE group vs 87%±2% of control, P<0.05), and simvastatin significantly reduced neutrophils (12.9%±2.0%, P<0.05) in the bronchoalveolar lavage fluid, but had no effect on macrophage (89%±1.6%, P>0.05). In response to CSE, MMP-8, MMP-9, and MMP-12 mRNA were upregulated more than sevenfold, while TIMP-1 and TIMP-4 increased two- to fivefold. Simvastatin significantly blocked upregulation of MMP-8 and -9 (P<0.01), but had no effect on MMP-12, TIMP-1 and TIMP-4 mRNA (P>0.05). In addition, simvastatin significantly blocked cigarette smoke-induced MMP-8 and -9 protein synthesis, while it had no significant effect on TIMP-1 and -4 protein synthesis even in the presence of cigarette smoke. CONCLUSION: CSE resulted in imbalance of MMPs and TIMPs, and by which mechanism, cigarette smoke may lead to insufficient lung tissue repair. Simvastatin partially blocked airway inflammation and MMP production and, thus, statins may modulate composition of the lung extracellular matrix.

Novel karyotypes of partial monosomy 21 and partial monosomy 1 and underlying etiology.

We report two novel karyotypes in the siblings of a Chinese family, 45,XY,der(1)t(1;21)(q44;q21)mat,-21 and 45,XX,der(1)t(1;21)(q44;q21)mat,-21. These karyotypes are the result of unbalanced inheritance of a maternal balanced reciprocal translocation 46,XX,t(1;21)(q44;q21). Both patients share a phenotype of intellectual disability, facial malformation, and infertility. The infertility is manifest by: azoospermia in the brother and recurrent spontaneous abortions (RSA) in the sister. Database search revealed recurrent copy number losses associated with these translocated regions. Here we propose that the partial deletion of the gene SMYD3 is responsible for both the intellectual disability in both patients, as well as the azoospermia in the male patient. Altogether, SMYD3 may be an important candidate gene for future research on male fertility.

Effect of Simvastatin on 5-HT and 5-HTT in a Rat Model of Pulmonary Artery Hypertension.

BACKGROUND/AIMS: To investigaterole of serotonin (5-HT) and serotonin transporter (5-HTT) in a rat model of cigarette smoke-induced pulmonary artery hypertension (PAH) and the effect of statins on regulating 5HT and 5-HTT. METHODS: A rat model of COPD comorbid with PAH was established by cigarette smoke exposure with or without simvastatin administration. The smoking and the simvastatin plus smoking groups were exposed to cigarette smoke daily, and the latter received simvastatin at 5mg/kg, once a day. After 16 weeks of cigarette smoke exposure, body weight and mean pulmonary arterial pressure (mPAP) were measured, bronchoalveolar lavage (BAL) was performed, and lung tissues and blood samples were collected to determine cardiopulmonary pathology, physiological indices, blood levelof 5-HT and expression of 5-HTT in the lung. RESULTS: In addition to alveolar structural damage (COPD-like injury), chronic cigarette smoke exposure lead to pulmonary artery remodeling and PAH as evidenced by significant elevation of mPAP, RVHI, WT%and WA%. Cigarette smoke exposure resulted in significant reduction in animal body weight, and simvastatin significantly prevented smoke-induced weight loss. The number of inflammatory cells in BALF was dramatically increased in smoke exposed rats, and simvastatin dampened the number of leukocytes, neutrophils, lymphocytes, and macrophages. In addition, circulating 5-HTand expression of 5-HTT in the lung were significantly increased in the smoked rats compared to control rats, and it was significantly reduced by simvastatin. Alteration of BALF inflammatory cells, 5-HT and 5-HTT was significantly correlated with changes of mPAP, RVHI, WT% and WA%. CONCLUSIONS: Cigarette smoke exposure could result in not only COPD, but also PAH, which may attribute to the alteration of blood 5-HT and lung tissue 5-HTT. Simvastatin could significantly inhibited 5-HT and 5-HTT expression, and by which mechanism, it may protect animals from development of PAH.