Combination of IVIM with DCE-MRI for diagnostic and prognostic evaluation of breast cancer.

PURPOSE: To identify the most effective combination of DCE-MRI (Ktrans,Kep) and IVIM (D,f) and analyze the correlations of these parameters with prognostic indicators (ER, PR, and HER2, Ki-67 index, axillary lymph node (ALN) and tumor size) to improve the diagnostic and prognostic efficiency in breast cancer. METHODS: This is a prospective study. We performed T1WI, T2WI, IVIM, DCE-MRI at 3 T MRI examinations on benign and malignant breast lesions that met the inclusion criteria. We also collected pathological results of corresponding lesions, including ER, PR, and HER2, Ki-67 index, axillary lymph node (ALN) and tumor size. The diagnostic efficacy of DCE-MRI, IVIM imaging, and their combination for benign and malignant breast lesions was assessed. Correlations between the DCE-MRI and IVIM parameters and prognostic indicators were assessed. RESULTS: Overall,59 female patients with 62 lesions (22 benign lesions and 40 malignant lesions) were included in this study. The malignant group showed significantly lower D values (p < 0.05) and significantly higher Ktrans, Kep, and f values (p < 0.05). The AUC values of DCE, IVIM, DCE + IVIM were 0.828, 0.882, 0.901. Ktrans, Kep, D and f values were correlated with the pathological grade (p < 0.05); Ktrans was negatively correlated with ER expression (r = -0.519, p < 0.05); Kep was correlated with PR expression and the Ki-67 index (r = -0.489, 0.330, p < 0.05); the DCE and IVIM parameters showed no significant correlations with the HER2 and ALN (p > 0.05). Tumor diameter was correlated with the Kep, D and f values (r = 0.246, -0.278, 0.293; p < 0.05). CONCLUSION: IVIM and DCE-MRI allowed differential diagnosis of benign and malignant breast lesions, and their combination showed significantly better diagnostic efficiency. DCE- and IVIM-derived parameters showed correlations with some prognostic factors for breast cancer.

Associations of environmental cadmium exposure with kidney damage: Exploring mediating DNA methylation sites in Chinese adults.

Environmental exposure is widely recognized as the primary sources of Cadmium (Cd) in the human body, and exposure to Cd is associated with kidney damage in adults. Nevertheless, the role of DNA methylation in Cd-induced kidney damage remains unclear. This study aimed to investigate the epigenome-wide association of environmental Cd-related DNA methylation changes with kidney damage. We included 300 non-smoking adults from the China in 2019. DNA methylation profiles were measured with Illumina Infinium MethylationEPIC BeadChip array. Linear mixed-effect model was employed to estimate the effects of urinary Cd with DNA methylation. Differentially methylated positions (DMPs) associated with urinary Cd were then tested for the association with kidney damage indicators. The mediation analysis was further applied to explore the potential DNA methylation based mediators. The prediction model was developed using a logistic regression model, and used 1000 bootstrap resampling for the internal validation. We identified 27 Cd-related DMPs mapped to 20 genes after the adjustment of false-discovery-rate for multiple testing among non-smoking adults. 17 DMPs were found to be associated with both urinary Cd and kidney damage, and 14 of these DMPs were newly identified within the Chinese. Mediation analysis revealed that DNA methylation of cg26907612 and cg16848624 mediated the Cd-related reduced kidney damage. In addition, ten variables were selected using the LASSO regression analysis and were utilized to develop the prediction model. It found that the nomogram model predicted the risk of kidney damage caused by environmental Cd with a corrected C-index of 0.779. Our findings revealed novel DMPs associated with both environmental Cd exposure and kidney damage among non-smoking adults, and developed an easy-to-use nomogram-illustrated model using these novel DMPs. These findings could provide a theoretical basis for formulating prevention and control strategies for kidney damage from the perspective of environmental pollution and epigenetic regulation.

Characteristics of the presence and migration patterns of DOM between ice and water in the cold and arid Daihai Lake.

Seasonal ice cover plays a crucial role in shaping the physical characteristics of lakes in cold and arid regions. Moreover, the ice significantly affects the level and quality of dissolved organic matter (DOM) in the water column. We utilized spectroscopy and mass spectrometry to analyze the molecular composition and distribution of DOM in ice cores and under-ice water in Daihai Lake. We identified the main environmental factors affecting DOM migration through structural equation modelling (SEM). The freezing process created a repulsive effect on DOM, with water samples demonstrating a greater DOM content than ice. The dominant part of the DOM in the ice cores was mainly comprised of protein-like materials (71.45 %), whereas water consisted of humus-like materials (54.81 %). The average molecular weight of the ice cover DOM (m/z = 396.77) was smaller than in the under-ice water (m/z = 405.42). While low-molecular and low-aromatic protein-like material tended to be trapped in the ice layer during ice formation, large-molecular and highly aromatic humic substances were more easily expelled into the water. Interestingly, condensed aromatic hydrocarbons were found to occur less frequently in the ice phase (11 %) compared to the aqueous phase (13 %). Both the lipid and protein/aliphatic compound structures exhibited slightly higher ratios in the ice (6 % and 8 %, respectively) than in water (1 % and 5 %, respectively). SEM between the ice cover environment and DOM indicated that the ice can influence the distribution pattern of DOM through the regulation of internal solute factors and other chemicals. The nature of the DOM and the rate of ice growth also play critical roles in determining the distribution mechanism of DOM for ice and water. The pollutant distribution characteristics and migration patterns between ice and water are essential for comprehending environmental water pollution and promoting pollution management and protection measures in cold region lakes.

Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis.

Objective: This study aimed to identify candidate gene biomarkers associated with immune infiltration in idiopathic pulmonary fibrosis (IPF) based on machine learning algorithms. Methods: Microarray datasets of IPF were extracted from the Gene Expression Omnibus (GEO) database to screen for differentially expressed genes (DEGs). The DEGs were subjected to enrichment analysis, and two machine learning algorithms were used to identify candidate genes associated with IPF. These genes were verified in a validation cohort from the GEO database. Receiver operating characteristic (ROC) curves were plotted to assess the predictive value of the IPF-associated genes. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm was used to evaluate the proportion of immune cells in IPF and normal tissues. Additionally, the correlation between the expression of IPF-associated genes and the infiltration levels of immune cells was examined. Results: A total of 302 upregulated and 192 downregulated genes were identified. Functional annotation, pathway enrichment, Disease Ontology and gene set enrichment analyses revealed that the DEGs were related to the extracellular matrix and immune responses. COL3A1, CDH3, CEBPD, and GPIHBP1 were identified as candidate biomarkers using machine learning algorithms, and their predictive value was verified in a validation cohort. Additionally, ROC analysis revealed that the four genes had high predictive accuracy. The infiltration levels of plasma cells, M0 macrophages and resting dendritic cells were higher and those of resting natural killer (NK) cells, M1 macrophages and eosinophils were lower in the lung tissues of patients with IPF than in those of healthy individuals. The expression of the abovementioned genes was correlated with the infiltration levels of plasma cells, M0 macrophages and eosinophils. Conclusion: COL3A1, CDH3, CEBPD, and GPIHBP1 are candidate biomarkers of IPF. Plasma cells, M0 macrophages and eosinophils may be involved in the development of IPF and may serve as immunotherapeutic targets in IPF.

The Effectiveness and Safety of Huangqi Xixin Decoction for Cough Variant Asthma: A Systematic Review and Meta-Analysis.

Objective: A comprehensive and systematic review is needed to evaluate the safety and effectiveness of Huangqi Xixin decoction (HQXXD) for cough variant asthma (CVA). In this systematic review, we comprehensively interrogate the safety and effectiveness of HQXXD for CVA. Methods: An overall search for studies in main English and Chinese electronic databases from their inception to June 30, 2022, was performed. Randomized controlled trials (RCTs) involving HQXXD for CVA were included. According to Cochrane Reviewer's Handbook, the risk of bias related to the included studies was evaluated. A meta-analysis using RevMan 5.4 software from the Cochrane Collaboration was used to integrate the outcomes of the included RCTs. Results: A systematic review and meta-analysis were conducted using the seven eligible RCTs that had been retrieved. The included RCT-related risk of bias was evaluated. According to the findings of the meta-analysis, the HQXXD group had significantly higher total effective rates of clinical efficacy and airway responsiveness, and a significantly lower recurrence rate in comparison with the conventional Western medicine treatment group. Conclusion: In the treatment of CVA patients, HQXXD is safe and effective, which benefits clinical efficacy and airway responsiveness, reduces the recurrence rate, and has no adverse effects.

A novel defined cuproptosis-related gene signature for predicting the prognosis of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) has become the most prevalent histologic subset of primary lung cancer, and effective innovative prognostic models are needed to enhance the feasibility of targeted therapies for the disease. Programmed cell death (PCD) performs an integral function in the origin and treatment of cancer. Some PCD-related effective signatures for predicting prognosis in LUAD patients could provide potential therapeutic options in LUAD. A copper-dependent cell death referred to as cuproptosis is distinct from known PCD. However, whether cuproptosis is associated with LUAD patients' prognoses and the potential roles of cuproptosis-related genes involved is still unknown. For the prediction of LUAD prognosis, we developed a unique cuproptosis-associated gene signature. In The Cancer Genome Atlas (TCGA) cohort, the score derived from the risk signature on the basis of six cuproptosis-related genes was found to independently serve as a risk factor for anticipating lung cancer-related death. The differentially expressed genes between the high- and low-risk groups were linked to the cilium-related function. LUAD patients' prognoses may now be predicted by a unique gene signature identified in this work. This discovery also provides a substantial foundation for future research into the links between cuproptosis-associated genes and cilium-related function in LUAD patients.

Danggui Buxue Decoction Ameliorates Idiopathic Pulmonary Fibrosis through MicroRNA and Messenger RNA Regulatory Network.

OBJECTIVE: To develop a putative microRNA (miRNA) and messenger RNA (mRNA) regulatory network of Danggui Buxue decoction's (DGBXD) amelioration of idiopathic pulmonary fibrosis (IPF). METHODS: The Gene Expression Omnibus (GEO) database was used to identify differentially expressed miRNAs (DE-miRNAs) and differentially expressed mRNAs (DE-mRNAs). Using miRNet, the predicted target genes of identified DE-miRNAs were estimated, and then the target genes of DE-miRNAs in IPF were comprehensively examined. The Enrichr database was used to conduct functional enrichment and pathway enrichment. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was employed to obtain the target genes of DGBXD as well as active compounds. A putative miRNA-mRNA regulatory network of DGBXD acting on IPF was developed by intersecting the target genes of DGBXD with the DE-miRNA target genes in IPF. A bleomycin-induced mouse model was established and used to perform histopathology as well as real-time quantitative polymerase chain reaction (qRT-PCR) analyses of some miRNA-mRNA pairs. RESULTS: Fourteen upmodulated DE-miRNAs and six downmodulated DE-miRNAs were screened. The downstream target genes of upmodulated and downmodulated DE-miRNAs were predicted. Subsequently, 1160 upmodulated DE-mRNAs and 1427 downmodulated DE-mRNAs were identified. Then, target genes of DE-miRNAs comprising 49 downmodulated and 53 upmodulated target genes were further screened to perform functional enrichment and pathway enrichment analyses. Subsequently, 196 target genes of DGBXD were obtained from TCMSP, with six downregulated target genes and six upregulated target genes of DGBXD acting on IPF being identified. A promising miRNA-mRNA regulatory network of DGBXD acting on IPF was developed in this study. Moreover, mir-493 together with its target gene Olr1 and mir-338 together with Hif1a were further validated by qRT-PCR. CONCLUSION: This study proposed detailed possible processes of miRNA-mRNA modulatory axis in IPF and constructed a prospective IPF-related miRNA-mRNA modulatory network with the aim of alleviating IPF with DGBXD.

Construction of a potential microRNA and messenger RNA regulatory network of acute lung injury in mice.

Acute lung injury (ALI) is a life-threatening clinical condition associated with critically ill patients, and the construction of potential microRNA (miRNA) and messenger RNA (mRNA) regulatory networks will help to fully elucidate its underlying molecular mechanisms. First, we screened fifteen upregulated differentially expressed miRNAs (DE-miRNAs) and six downregulated DE-miRNAs from the Gene Expression Omnibus (GEO) database. Then, the predicted target genes of the upregulated and downregulated DE-miRNAs were identified from the miRNet database. Subsequently, differentially expressed mRNAs (DE-mRNAs) were identified from the GEO database and subjected to combined analysis with the predicted DE-miRNA target genes. Eleven target genes of the upregulated DE-miRNAs and one target gene of the downregulated DE-miRNAs were screened out. To further validate the prediction results, we randomly selected a dataset for subsequent analysis and found some accurate potential miRNA-mRNA regulatory axes, including mmu-mir-7b-5p-Gria1, mmu-mir-486a-5p-Shc4 and mmu-mir-486b-5p-Shc4 pairs. Finally, mir-7b and its target gene Gria1 and mir-486b and its target gene Shc4 were further validated in a bleomycin-induced ALI mouse model. We established a potential miRNA-mRNA regulatory network of ALI in mice, which may provide a basis for basic and clinical research on ALI and advance the available treatment options.

Arctigenin prevents monocrotaline-induced pulmonary arterial hypertension in rats.

The hallmark features of the development of pulmonary arterial hypertension (PAH) include the proliferation of pulmonary vascular smooth muscle cells, oxidative stress, inflammation, and pulmonary artery remodeling. Arctigenin is a bioactive component of Arctium lappa that exerts anti-inflammatory and antiproliferative effects in several diseases; however, its effects on pulmonary arteries are still unclear. This study aimed to investigate the efficacy of arctigenin to prevent PAH. Rats injected with monocrotaline (MCT) progressively developed PAH. Arctigenin treatment (50 mg per kg per day, intra-peritoneally) ameliorated right ventricular systolic pressure and pulmonary arterial remodeling, decreased the expression of inflammatory cytokines, and limited the proliferation of pulmonary vascular smooth muscle cells in lungs. Mechanistically, arctigenin effectively inhibited the MCT-induced elevation of NLRP3, caspase-1, and interleukin 1-beta expression in the lungs. These results indicate that arctigenin ameliorates MCT-induced PAH, at least in part, through exerting its anti-inflammatory, antioxidant, and antiproliferative effects, which inhibit the NLRP3 inflammasome signal pathway in rats.

Vitamin D Supplementation in the Treatment of Chronic Heart Failure: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: In recent years, there has been growing evidence that vitamin D deficiency is associated with the development and progression of chronic heart failure (CHF). HYPOTHESIS: Additional supplementation of vitamin D may have protective effects in patients with CHF. METHODS: We searched PubMed, Embase, and Cochrane databases through June 2015 and included 7 randomized controlled trials that investigated the effects of vitamin D on cardiovascular outcomes in patients with CHF. Then, we performed a meta-analysis of clinical trials to confirm whether vitamin D supplementation is beneficial in CHF patients. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated using fixed- or random-effects models. RESULTS: Our pooled results indicated that additional supplementation of vitamin D was not superior to conventional treatment in terms of left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and 6-minute walk distance. Moreover, vitamin D supplementation was associated with significant decreases in the levels of tumor necrosis factor-α (WMD: -2.42 pg/mL, 95% CI: -4.26 to -0.57, P < 0.05), C-reactive protein (WMD: -0.72 mg/L, 95% CI: -1.42 to -0.02, P < 0.05), and parathyroid hormone (WMD: -13.44 pg/mL, 95% CI: -21.22 to -5.67, P < 0.05). CONCLUSIONS: Vitamin D supplementation may decrease serum levels of parathyroid hormone and inflammatory mediators in CHF patients, whereas it has no beneficial effects on improvement of left ventricular function and exercise tolerance.

Long non-coding RNA PVT1 as a novel biomarker for diagnosis and prognosis of non-small cell lung cancer.

Accumulating evidence has indicated that long non-coding RNA PVT1 is upregulated in various human cancers. However, it remains unclear whether PVT1 is involved in the development and progression of non-small cell lung cancer (NSCLC). The present study was designed to investigate the expression, biological role, and clinical significance of PVT1 in NSCLC. Our results indicated that PVT1 expression was significantly increased in NSCLC tissues and cell lines, and its upregulation was associated with advanced T-stage and tumor-node-metastasis (TNM) stage and regional lymph node metastasis. PVT1 expression levels were robust in differentiating NSCLC tissues from controls. Kaplan-Meier curve and Cox regression analysis showed that high expression of PVT1 was associated with poor overall survival and disease-free survival in NSCLC patients. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays indicated that knockdown of PVT1 remarkably inhibited NSCLC cell proliferation, whereas overexpression of PVT1 significantly promoted cellular proliferation. In addition, PVT1 knockdown increased the number of cells in the G0/G1 phase and reduced the number of cells in the S phase, while overexpression of PVT1 could promote cell cycle progression. Furthermore, our findings also revealed that the messenger RNA (mRNA) and protein expression of P15 and P21 was significantly upregulated in NSCLC cells transfected with PVT1 small interfering RNA (siRNA) and downregulated in cells transfected with pcDNA3.1-PVT1. In conclusion, our study demonstrated that PVT1 might serve as a promising biomarker for diagnosis and prognosis of NSCLC, and it could promote the proliferation of NSCLC cells by downregulating p15 and p21 expression.

The plasma lncRNA acting as fingerprint in non-small-cell lung cancer.

Recent studies have indicated that long non-coding RNAs (lncRNAs) could act as non-invasive tumor markers in both diagnosis and predicting the prognosis. In this study, we focused to determine the expression of circulating lncRNAs in patients suffering from non-small-cell lung cancer (NSCLC), aiming to found the potential lncRNA as predictor. Twenty-one lncRNAs which previously identified were selected as candidate targets for subsequent circulating lncRNA assay. The candidate lncRNAs were validated by qRT-PCR arranged in the training and validation sets. Circulating SPRY4-IT1, ANRIL, and NEAT1 were significantly increased in plasma samples of NSCLC patients during training set and validation set. Receiver operating characteristic curve (ROC) analysis revealed that plasma ANRIL provided the highest diagnostic performance with an area under ROC curve value (AUC) of 0.798. Further combination with the three factors indicated a higher power (AUC, 0.876; sensitivity, 82.8 %; specificity, 92.3 %). The stableness detection of the three factors indicated that circulating SPRY4-IT1, ANRIL, and NEAT might serve as a predictor for the early warning of non-small-cell lung cancer.

MicroRNA-19a regulates lipopolysaccharide-induced endothelial cell apoptosis through modulation of apoptosis signal-regulating kinase 1 expression.

BACKGROUND: MicroRNAs, small non-encoding RNAs that post-transcriptionally modulate expression of their target genes, have been implicated as critical regulatory molecules in endothelial cells. RESULTS: In the present study, we found that overexpression of miR-19a protects endothelial cells from lipopolysaccharide (LPS)-induced apoptosis through the apoptosis signal-regulating kinase 1 (ASK1)/p38 pathway. Quantitative real-time PCR demonstrated that the expression of miR-19a in endothelial cell was markedly down-regulated by LPS stimulation. Furthermore, LPS-induced apoptosis was significantly inhibited by over-expression of miR-19a. Finally, both a luciferase reporter assay and western blot analysis showed that ASK1 is a direct target of miR-19a. CONCLUSIONS: MiR-19a regulates ASK1 expression by targeting specific binding sites in the 3' untranslated region of ASK1 mRNA. Overexpression of miR-19a is an effective method to protect against LPS-induced apoptosis of endothelial cells.