Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study.

BACKGROUND: The question as to whether or not diabetes mellitus increases the risk of idiopathic pulmonary fibrosis (IPF) remains controversial. This study aimed to investigate the causal association between type 1 diabetes (T1D), type 2 diabetes (T2D), and IPF using Mendelian randomization (MR) analysis. METHODS: We used two-sample univariate and multivariate MR (MVMR) analyses to investigate the causal relationship between T1D or T2D and IPF. We obtained genome-wide association study (GWAS) data for T1D and T2D from the European Bioinformatics Institute, comprising 29,652 T1D samples and 101,101 T1D single nucleotide polymorphisms (SNPs) and 655,666 T2D samples and 5,030,727 T2D SNPs. We also used IPF GWAS data from the FinnGen Biobank comprising 198,014 IPF samples and 16,380,413 IPF SNPs. All cases and controls in these datasets were derived exclusively from European populations. In the univariate MR analysis, we employed inverse variance-weighted (IVW), weighted median (WM), and MR-Egger regression methods. For the MVMR analysis, we used the multivariate IVW method primarily, and supplemented it with multivariate MR-Egger and multivariate MR- least absolute shrinkage and selection operator methods. Heterogeneity tests were conducted using the MR-IVW and MR-Egger regression methods, whereas pleiotropic effects were assessed using the MR-Egger intercept. The results of MR and sensitivity analyses were visualized using forest, scatter, leave-one-out, and funnel plots. RESULTS: Univariate MR revealed a significant causal relationship between T1D and IPF (OR = 1.118, 95% CI = 1.021-1.225, P = 0.016); however, no significant causal relationship was found between T2D and IPF (OR = 0.911, 95% CI = 0.796-1.043, P = 0.178). MVMR analysis further confirmed a causal association between T1D and IPF (OR = 1.133, 95% CI = 1.011-1.270, P = 0.032), but no causal relationship between T2D and IPF (OR = 1.009, 95% CI = 0.790-1.288, P = 0.950). Sensitivity analysis results validated the stability and reliability of our findings. CONCLUSION: Univariate and multivariate analyses demonstrated a causal relationship between T1D and IPF, whereas no evidence was found to support a causal relationship between T2D and IPF. Therefore, in clinical practice, patients with T1D should undergo lung imaging for early detection of IPF.

Yellow nail syndrome accompanied by minimal-change nephrotic syndrome: A case report.

BACKGROUND: In most cases of yellow nail syndrome (YNS), the classic triad of yellow nails, lymphedema and respiratory manifestations rarely manifest simultaneously. Therefore, diagnosis is delayed or frequently missed. CASE SUMMARY: We report a 62-year-old YNS patient presenting with bilateral pleural, pericardial and peritoneal effusions who, 2 mo later, developed minimal-change nephrotic syndrome. After treatment with vitamin E, clarithromycin and prednisone for 3 mo, effusions in the chest, pericardium and abdominal cavity decreased while urine protein levels returned to within normal ranges. CONCLUSION: Clinicians should consider the possibility of YNS for patients presenting with multiple serous effusions and nephrotic syndromes.

Disturbance of serum lipid metabolites and potential biomarkers in the Bleomycin model of pulmonary fibrosis in young mice.

BACKGROUND: Altered metabolic pathways have recently been considered as potential drivers of idiopathic pulmonary fibrosis (IPF) for the study of drug therapeutic targets. However, our understanding of the metabolite profile during IPF formation is lacking. METHODS: To comprehensively characterize the metabolic disorders of IPF, a mouse IPF model was constructed by intratracheal injection of bleomycin into C57BL/6J male mice, and lung tissues from IPF mice at 7 days, 14 days, and controls were analyzed by pathology, immunohistochemistry, and Western Blots. Meanwhile, serum metabolite detections were conducted in IPF mice using LC-ESI-MS/MS, KEGG metabolic pathway analysis was applied to the differential metabolites, and biomarkers were screened using machine learning algorithms. RESULTS: We analyzed the levels of 1465 metabolites and found that more than one-third of the metabolites were altered during IPF formation. There were 504 and 565 metabolites that differed between M7 and M14 and controls, respectively, while 201 differential metabolites were found between M7 and M14. In IPF mouse sera, about 80% of differential metabolite expression was downregulated. Lipids accounted for more than 80% of the differential metabolite species with down-regulated expression. The KEGG pathway enrichment analysis of differential metabolites was mainly enriched to pathways such as the metabolism of glycerolipids and glycerophospholipids. Eight metabolites were screened by a machine learning random forest model, and receiver operating characteristic curves (ROC) assessed them as ideal diagnostic tools. CONCLUSIONS: In conclusion, we have identified disturbances in serum lipid metabolism associated with the formation of pulmonary fibrosis, contributing to the understanding of the pathogenesis of pulmonary fibrosis.

Diffuse pulmonary lymphangiomatosis: A rare case report in an adult.

RATIONALE: Diffuse pulmonary lymphangiomatos (DPL) is a rare aggressive lymphatic disorder characterized by proliferation of anastomozing lymphatic vessels and extremely rare in adult patients. PATIENT CONCERNS: We report a case of diffuse pulmonary lymphangiomatosis in 59-year-old man presented with cough and sputum for 2 months. DIAGNOSES: Combining clinical manifestations with results of radiological, bronchoscopy, and surgical lung biopsy, it was consistent with the diagnosis of DPL. INTERVENTIONS: After bronchoalveolar lavage and biopsy, symptom of cough got worse suddenly accompanied by excessive chyloptysis. The patient received an emergency surgical intervention and low fat medium chain fat treatment. OUTCOMES: The patient was discharged with a much better health condition. LESSONS: This case report is the oldest patient reported in the English literature, to the best of our knowledge. Serious complications of bronchoscopy should be considered, especially in DPL patients with severely enlarged mediastinum or with thin-walled translucent vesicles under endoscopy.

LINC00702 suppresses proliferation and invasion in non-small cell lung cancer through regulating miR-510/PTEN axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been consistently reported to be involved in the progression of non-small cell lung cancer (NSCLC). In this study, we aimed to identify aberrantly expressed lncRNAs in NSCLC, in order to explore new therapeutic targets for NSCLC. METHODS: Two pairs of NSCLC and adjacent normal tissues were first analyzed by RNA sequencing. The expressions of LINC00702 in 40 pairs patient samples and in 4 NSCLC cell lines was measured by quantitative real-time PCR. Putative target miRNAs of LINC00702 were predicted by the bioinformatics tools. The effect of LINC00702 on tumor growth in vivo was evaluated. RESULTS: LINC00702 was significantly down-regulated in patients with NSCLC, which was correlated with tumor size and metastasis. In addition, overexpression of LINC00702 markedly suppressed proliferation and metastasis in NSCLC cells via inducing apoptosis in vitro and in vivo. Moreover, bioinformatics and luciferase reporter assays demonstrated that LINC00702 functioned as a competing endogenous RNA (ceRNA) for miR-510 in NSCLC, and upregulated its target gene PTEN. CONCLUSION: Our results indicated that LINC00702 modulated the expression of PTEN gene by acting as a ceRNA for miR-510 in NSCLC. Therefore, LINC00702 may serve as a potential target for the diagnosis and treatment of patients with NSCLC.

Expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)/Tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary diseases and their relationships with pulmonary vascular remodelling.

OBJECTIVE: This study aims at investigating the expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)/ tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary disease (COPD) and their relationships with pulmonary vascular remodelling (PVR). METHODS: 60 para-tumour tissues were divided into the COPD group and the control group (n=30); the inflammations, pulmonary artery wall area/total artery area (WA%), and wall thickness/vascular outer diameter (WT%) were compared. The expressions of TLR-4, MMP-9/TIMP-1, and PCNA in pulmonary vascular smooth muscle cells were detected, and their relationships with PVR were then analysed. RESULTS: The inflammations (1.6±0.8), WA% (44.0±6.4), and WT% (27.3±3.3) in the COPD group were higher than in the control group (0.3±0.5, 26.1±2.8, 15.6±1.8), and the expressions of TLR-4 (31.4±147) and MMP-9/TIMP-1 (2.2±2.6) were increased compared to the control group (4.7±4.5, 1.9±12). Correlation analysis: TLR-4 and MMP-9/TIMP-1 were positively correlated with the inflammations (r=0.18, P<0.01), WA% (r=0.68, P<0.01), and WT% (r=0.73, P<0.01), as well as positively correlated with the expression of PCNA (r=0.44, P<0.01); the upregulation of TLR-4 was positively correlated with the expressions of MMP-9 and TIMP-1. CONCLUSIONS: The upregulation of TLR-4 in the pulmonary arterial smooth muscle cells of COPD patients could promote the inflammations and the MMP-9 expression, thus causing abnormal degradation of extracellular matrix, so it played an important role in the process of PVR.

Expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)/Tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary diseases and their relationships with pulmonary vascular remodelling

SUMMARY OBJECTIVE: This study aims at investigating the expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)/ tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary disease (COPD) and their relationships with pulmonary vascular remodelling (PVR). METHODS: 60 para-tumour tissues were divided into the COPD group and the control group (n=30); the inflammations, pulmonary artery wall area/total artery area (WA%), and wall thickness/vascular outer diameter (WT%) were compared. The expressions of TLR-4, MMP-9/TIMP-1, and PCNA in pulmonary vascular smooth muscle cells were detected, and their relationships with PVR were then analysed. RESULTS: The inflammations (1.6±0.8), WA% (44.0±6.4), and WT% (27.3±3.3) in the COPD group were higher than in the control group (0.3±0.5, 26.1±2.8, 15.6±1.8), and the expressions of TLR-4 (31.4±147) and MMP-9/TIMP-1 (2.2±2.6) were increased compared to the control group (4.7±4.5, 1.9±12). Correlation analysis: TLR-4 and MMP-9/TIMP-1 were positively correlated with the inflammations (r=0.18, P<0.01), WA% (r=0.68, P<0.01), and WT% (r=0.73, P<0.01), as well as positively correlated with the expression of PCNA (r=0.44, P<0.01); the upregulation of TLR-4 was positively correlated with the expressions of MMP-9 and TIMP-1. CONCLUSIONS: The upregulation of TLR-4 in the pulmonary arterial smooth muscle cells of COPD patients could promote the inflammations and the MMP-9 expression, thus causing abnormal degradation of extracellular matrix, so it played an important role in the process of PVR.

RESUMO OBJETIVO: Este estudo tem como objetivo investigar as expressões de TOLL-like receptor 4 (TLR-4) e metaloproteinase 9 da matriz (MMP-9)/inibidor de tecido da metaloproteinase 1 (TIMP-1) em vasos sanguíneos pulmonares com doença pulmonar obstrutiva crônica (DPOC) e suas relações com o remodelamento vascular pulmonar (PVR). MÉTODOS: Sessenta tecidos paratumorais foram divididos em grupo COPD e o grupo controle (n = 30). Foram comparadas as inflamações, área da parede da artéria pulmonar/área da artéria total (WA%) e espessura da parede/diâmetro externo vascular (WT%). As expressões de TLR-4, MMP-9/TIMP-1 e PCNA em células de músculo liso vascular pulmonar foram detectadas, e suas relações com PVR foram então analisadas. RESULTADOS: As inflamações (1,6 ± 0,8), WA% (44,0 ± 6,4) e WT% (27,3 ± 3,3) no grupo COPD foram maiores que no grupo controle (0,3 ± 0,5; 26,1 ± 2,8; 15,6 ± 1,8). E as expressões de TLR-4 (31,4 ± 14,7) e MMP-9/TIMP-1 (2,2 ± 2,6) foram aumentadas em relação ao grupo controle (4,7 ± 4,5, 1,9 ± 1,2). Na análise de correlação, TLR-4 e MMP-9/TIMP-1 foram positivamente correlacionadas com as inflamações (r = 0,18; P <0,01), WA% (r = 0,68; P <0,01) e WT% (r = 0,73; P <0,01), bem como correlacionadas positivamente com a expressão de PCNA (r = 0,44; P <0,01). A elevação da TLR-4 foi correlacionada positivamente com as expressões de MMP-9 e TIMP-1. CONCLUSÕES: A regulação positiva do TLR-4 nas células do músculo liso arterial pulmonar de pacientes com DPOC poderia promover as inflamações e a expressão de MMP-9, causando assim uma degradação anormal da matriz extracelular, por isso desempenhou um papel importante no processo de PVR.