Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma.

BACKGROUND Lung adenocarcinoma (LUAD) is a type of non-small cell carcinoma. Its pathogenesis is being explored and there is no cure for the disease. MATERIAL AND METHODS The Gene Expression Omnibus (GEO) was searched to obtain data on expression of messenger RNA. GEO2R, an interactive web tool, was used to calculate the differentially expressed genes (DEGs) in LUAD. All the DEGs from different datasets were imported into VENNY 2.1 (https://bioinfogp.cnb.csic.es/tools/venny/index.html) to identify the intersection of the DEGs. An online analysis tool, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), was used to help understand the biological meaning of DEG enrichment in LUAD. Cytoscape 3.7.2 was used to perform centrality analysis and visualize hub genes and related networks. Furthermore, the prognostic value of the hub genes was evaluated with the Kaplan-Meier plotter survival analysis tool. RESULTS The GEO database was used to obtain RNA sequencing information for LUAD and normal tissue from the GSE118370, GSE136043, and GSE140797 datasets. A total of 376 DEGs were identified from GSE118370, 248 were identified from GSE136403, and 718 DEGs were identified from GSE140797. The 10 genes with the highest degrees of expression - the hub genes - were CAV1, TEK, SLIT2, RHOJ, DGSX, HLF, MEIS1, PTPRD, FOXF1, and ADRB2. In addition, Kaplan-Meier survival evaluation showed that CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1, and ADRB2 were associated with favorable outcomes for LUAD. CONCLUSIONS CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1, and ADRB2 are hub genes in the DEG interaction network for LUAD and are involved in the development of and prognosis for the disease. The mechanisms underlying these genes should be the subject of further studies.

The Effects of Nebulized Inhaled Triptolide on Airway Inflammation in a Mouse Model of Asthma.

Inhalation of nebulized TP has received little attention in the past. Here, we intend to investigate the effect of nebulized inhaled TP on airway inflammation in a mouse model of asthma. 29 SPF BALB/c mice were divided into four groups: blank control (Blk, n = 5), normal saline (NS, n = 8), dexamethasone (Dex, n = 8), and TP (n = 8). During the process of sensitization, mice in the three intervention groups were treated with nebulized NS, an injection of Dex, and nebulized triptolide, respectively. Then bronchoalveolar lavage fluid (BALF), peripheral blood, and lung tissue were collected. Relevant cytokines, transcriptional factors, and CD4+Th17+ T cell proportions were assessed and compared. IL-6, IL-17, IL-23, and TGF-ß1 demonstrated a significant difference between groups in the following order: Dex < TP < NS (P ≤ 0.001), while IL-10 changed in the opposite direction (P < 0.001). At the transcriptional level in lung tissue, the Ct value of IL-17 in the Dex group was significantly higher than in the NS and TP groups (P < 0.001). Meanwhile, it was higher in the TP group than in the NS group (P < 0.001). The Ct value of RORγt demonstrated a significant difference among three groups in the following order: Dex > TP > NS (P < 0.001). An opposite trend of FoxP3 Ct value was revealed in the order: NS > TP > Dex. The proportion of CD4+Th17+ cells was 9.53 ± 2.74% in the NS group, 4.23 ± 2.26% in the Dex group, and 6.76 ± 2.99% in the TP group, which shows significant differences between the NS and Dex (P < 0.001) or NS and TP groups (P < 0.05). Inhalation of nebulized triptolide can play a role in suppressing airway inflammation with inflammatory cytokines and transcriptional factors reduced and CD4+Th17+ T cells dampened, also in a manner less than injected dexamethasone.

The Predictive Value of microRNA-134 and microRNA-1233 for the Early Diagnosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Pulmonary Embolism.

Background: The differential diagnosis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with acute pulmonary embolism (APE) complications are difficult because of the variability of clinical presentations and the shortage of an unfailing screening biomarkers or instruments. Objective: Aimed to detect and compare the expression of serum microRNAs (miR-1233, miR-134) in AECOPD patients complicated with APE. Patients/Methods: Blood samples were collected from 52 AECOPD patients (13 patients with APE complications, 39 patients without APE) and 10 patients with stable COPD. Serum miRNAs expression was detected with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The levels of plasma D-dimers were determined by detection with an enzyme-linked immunosorbent assay (ELISA). The receiver-operator characteristic (ROC) curve was used for evaluating the diagnostic accuracy of the studied miRNAs. Results: According to the Wells score, 42 of the 52 AECOPD patients were unlikely to have APE (≤4 points), whereas the remaining 10 (>4 points) were likely to have APE. There were 4 cases (4/13 30.8%) in the AECOPD combined with APE group with a Wells score of >4 points. The expression levels of miR-1233 and miR-134 in the serum were considerably upregulated in the AECOPD+APE group compared with the AECOPD group and the stable COPD group (P<0.05). The areas under the curve (AUCs) for miR-134 and miR-1233 were, respectively, 0.931 (95% CI 0.863-0.999) (P<0.05) and 0.884 (95% CI 0.79-0.978) (P<0.05) and were higher compared with the AUC for D-dimer of 0.628 (95% CI 0.447-0.809), the AUC for age-adjusted D-dimer of 0.705 (95% CI 0.525-0.885) and the AUC for Wells score of 0.577 (95% CI 0.389-0.765). Conclusion: Our study indicated that serum miR-1233 and miR-134 have high clinical value in the early diagnosis of AECOPD patients combined with APE, or could be used as potential biomarkers for clinical identification of AECOPD with or without APE complication.

Improved Early Recognition of Coronavirus Disease-2019 (COVID-19): Single-Center Data from a Shanghai Screening Hospital.

BACKGROUND: In December 2019, an outbreak of a novel coronavirus disease (COVID-19; previously known as 2019-nCoV) was reported in Wuhan, Hubei province, China, which has subsequently affected more than 200 countries worldwide including Europe, North America, Oceania, Africa and other places. The number of infected people is rapidly increasing, while the diagnostic method of COVID-19 is only by nucleic acid testing. OBJECTIVE: To explain the epidemiological characteristics, clinical features, imaging manifestations and to judge diagnostic value of COVID-19 by analyzing the clinical data of COVID-19 suspected and confirmed patients in a non-outbreak, Shanghai, China. To clarify the early epidemiology and clinical characteristics about COVID-19. METHODS: Cross-sectional, single-center case reports of the 86 patients screened at Zhoupu Hospital in Pudong New District, Shanghai, China, from January 23 to February 16, 2020. Epidemiology, demography, clinical, laboratory and chest CTs were collected and analyzed. The screened patients were divided into COVID-19 and non-COVID-19 based on nucleic acid test results. RESULTS: Of the 86 screened patients, 11 were confirmed (12.8%) by nucleic acid testing (mean age 40.73 ± 11.32, 5 males). No significant differences were found in clinical symptoms including fever, cough, dyspnea, sore throat, and fatigue (P > 0.05). No statistical difference was observed in plasma C-reactive protein (CRP) between the two groups (COVID-19 and non-COVID-19 ) of patients (P = 0.402), while the white blood cell count and lymphocyte count of the confirmed patients were slightly lower than those of the suspected patients (P < 0.05). Some non-COVID-19 chest CTs also showed subpleural lesions, such as ground-glass opacities (GGO) combined with bronchiectasis; or halo nodules distributed under the pleura with focal GGO; consolidation of subpleural distribution or combined with air bronchi sign and vascular bundle sign, etc. CONCLUSION: The early clinical manifestations and imaging findings of COVID-19 are not characteristic in non-outbreak areas. Etiological testing should be performed as early as possible for clinically suspected patients.

Association study of genetic variations of inflammatory biomarkers with susceptibility and severity of obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) increases health risks of cardiovascular disease and stroke. Both genetic factors and environmental exposures contribute to the occurrence of OSA. The purpose of this study was to determine the role of four functional inflammatory single nucleotide polymorphisms (SNPs) (VWF rs1063856, IL-6 rs1800796, TNF rs1800629, and CRP rs2794521) in the susceptibility and severity of OSA. METHODS: A case-control study of OSA among Chinese population was conducted. Genotyping was performed using ABI TaqMan SNP genotyping technique. RESULTS: We found VWF rs1063856 (OR = 1.50, 95% CIs = 1.10-2.04; p = 0.010), IL-6 rs1800796 (OR = 1.32, 95% CIs = 1.11-1.56; p = 0.002), TNF rs1800629 (OR = 1.44, 95% CIs = 1.13-1.83; p = 0.003), and CRP rs2794521 (OR = 1.27, 95% CIs = 1.04-1.55; p = 0.021) were all significantly associated with increased susceptibility of OSA, while VWF rs1063856 (OR = 1.75, 95% CIs = 1.18-2.62; p = 0.006), IL-6 rs1800796 (OR = 1.39, 95% CIs = 1.10-1.76; p = 0.006) were associated with the severity of OSA. CONCLUSIONS: Our study indicated that functional variants of inflammatory biomarkers could cause the occurrence of OSA and influence the severity of OSA. These findings further support that inflammatory cytokines were closely related to the occurrence and development of OSA.

The SNPs (-1654C/T, -1641A/G and -1476A/T) of protein C promoter are associated with susceptibility to pulmonary thromboembolism in a Chinese population.

BACKGROUND: Pulmonary thromboembolism (PTE) is a common and potentially lethal disease. It is significant to investigate the gene mutations of protein C for clarifying the etiology of PTE. In this present study, we investigated the promoter region polymorphism sites including -1654C/T, -1641A/G and -1476A/T of the protein C gene in a Chinese population. METHODS: A total of 110 cases of PTE and one hundred and ninety healthy controls in a Chinese population were genotyped for three polymorphisms (-1654C/T, -1641A/G and -1476A/T) of the protein C promoter. The statistical analysis was performed by Stata 11.0. RESULTS: The single nucleotide polymorphisms (SNPs) (-1654C/T, -1641A/G and -1476A/T) in protein C gene were associated with the susceptibility to PTE in Chinese population. According to the binary logistic regression analysis, the independently significant risk factors for PTE were the complications of deep vein thrombosis (DVT) or cancer, history of operation or injury, and the homozygous carriers of the TT genotype (protein C -1654C/T). CONCLUSIONS: The SNPs (-1654C/T, -1641A/G and -1476A/T) of protein C promoter gene are associated with the susceptibility to PTE in a Chinese population. Especially, the homozygous carriers of genotype TT (-1654C/T) increase the risk of PTE in a Chinese population. Confirmation of our preliminary observations in a larger scale study is needed.

Protein C polymorphism and susceptibility to PTE in China.

Pulmonary thromboembolism (PTE) is a common clinical problem that is associated with substantial morbidity and mortality. We investigated the role of protein C polymorphism in patients with PTE in order to find out the correlation between its polymorphism and the susceptibility of the Chinese population to develop PTE. We used a case-control study design. Sixty-three consecutive patients with PTE were enrolled as the investigated group and 86 healthy people as the control group. Two novel polymorphisms, C/T at the position of 2405 and A/G at the position of 2418in the protein C gene promoter region were detected through PCR-restriction fragment length polymorphism analysis. The results suggested that the genotype frequencies of the two single-nucleotide polymorphisms (SNPs) when combined together were not significantly different between the case and control group (P > 0.05). However, the allele frequency of the C2405T SNP was significantly different between the case and control group. The frequency of T allele in the PTE group was higher when compared to the control, whereas the frequency of C allele was lower (P < 0.05). These results suggested that there were six different kinds of genotype distribution (TA-TA, TA-CA, TA-CG, CG-CG, CA-CG, CA-CA) and three different kinds of haplotype (TA, CG, CA). Our result showed that the frequency of the TA haplotype was significantly higher in the patients suffering from PTE (P < 0.05). These results suggest that the two polymorphisms present in the control region of the protein C gene are associated with an increased susceptibility to PTE in the Chinese population. The 2405T allele may be a possible risk factor for the development of PTE, whereas the C allele may probably be a protective factor of PTE Moreover, the TA haplotype may also be associated with an increased risk for developing PTE.