Background
Asthma is a heterogeneous disease that can be divided into four inflammatory phenotypes: eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma (MGA), and paucigranulocytic asthma (PGA). While research has mainly focused on EA and NA, the understanding of PGA is limited. In this study, we aimed to identify underlying mechanisms and hub genes of PGA.
Methods
Based on the dataset from Gene Expression Omnibus(GEO), weighted gene coexpression network analysis (WGCNA), differentially expressed genes (DEGs) analysis and protein–protein interaction (PPI) network analysis were conducted to construct a gene network and to identify key gene modules and hub genes. Functional enrichment analyses were performed to investigate the biological process, pathways and immune status of PGA. The hub genes were validated in a separate dataset.
Results
Compared to non-PGA, PGA had a different gene expression pattern, in which 449 genes were differentially expressed. One gene module significantly associated with PGA was identified. Intersection between the differentially expressed genes (DEGs) and the genes from the module that were most relevant to PGA were mainly enriched in inflammation and immune response regulation. The single sample Gene Set Enrichment Analysis (ssGSEA) suggested a decreased immune infiltration and function in PGA. Finally six hub genes of PGA were identified, including ADCY2, CXCL1, FPRL1, GPR109B, GPR109A and ADCY3, which were validated in a separate dataset of GSE137268.
Conclusions
Our study characterized distinct gene expression patterns, biological processes and immune status of PGA and identified hub genes, which may improve the understanding of underlying mechanism and provide potential therapeutic targets for PGA.
Background: En bloc excision is increasingly used for the management of giant cell tumor in the distal radius. Osteoarticular allograft is extensively used for decades, also custom-made prosthesis reconstruction is recently applied widely. We aimed to firstly compare the clinical outcomes of the two procedures. Methods: We retrospectively analyzed thirty-two patients with Campanacci III or recurrent GCT of the distal radius for follow-up at a mean of 33.2 months. Sixteen underwent osteoarticular allograft reconstruction (allograft group) and sixteen received cementless three-dimensional(3D)-printed prosthesis reconstruction (prosthesis group) between March 18, 2013, and May 20, 2018. All patients were assessed by clinical and radiological examinations, including pre- and postoperative active range of motion (ROM) of the wrist, VAS score, grip strength, degenerative change of wrist, Mayo wrist score and Musculoskeletal Tumor Society (MSTS) score. Complications were evaluated on the Henderson classification. Results: Both groups showed significantly increased ROM, grip strength, Mayo score and MSTS score postoperatively. MSTS and Mayo score were significantly higher in prosthesis group. There was no significant difference in grip strength and VAS between two groups. In allograft group, one had a local recurrence; one had a late infection; four had wrist subluxation. All patients had degenerative changes (mean 9 months, 95% CI: 8.03-9.97). One had resorption of allograft without allograft bone fracture. In the prosthesis group, one had a local recurrence. Three developed wrist subluxation. Three had separation of the distal radioulnar joint. None of the patients developed degeneration of wrist. Conclusions: Our study firstly compared the objective functional outcomes and complications of two reconstructive methods for the Campanacci III or recurrent GCT in the distal radius. 3D-printed prosthesis replacement can preserve better wrist function than allograft reconstruction at short-term. During 3D-printed prosthesis design, preoperative morphological assessment of affected proximal row carpal is helpful to control the postoperative dislocation. After allograft reconstruction, degeneration of wrist, which has been proved in all patients, severely influence their wrist function. Therefore, compared with allograft reconstruction, 3D-printed prosthesis reconstruction shows its irreplaceable advantages at early-stage application, especially in wrist function, but its larger cases research at longer follow-up are needed.
Objective: VEGF-D is a potential biomarker for lymphangioleiomyomatosis (LAM); however, its diagnostic performance has yet to be systematically studied. Methods: We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library to identify primary studies on VEGF-D in relation to the diagnosis of LAM. The quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Summary estimates of diagnostic accuracy were pooled using a bivariate random effects model. Subgroup and sensitivity analyses were performed to explore possible heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was applied to rate the quality of evidence and indicate the strength of recommendations. Results: Ten studies involving 945 patients were of high risk in quality, as assessed using the QUADAS-2. The pooled diagnostic parameters were indicated as follows: sensitivity = 0.82 (95% CI, 0.71-0.90); specificity = 0.98 (95% CI, 0.94-0.99); and diagnostic OR = 197 (95% CI, 66-587). The AUC of summary ROC analysis was 0.98. The subgroup and sensitivity analyses revealed that the overall performance was not substantially affected by the composition of the control group, prespecified cutoff value, the country of origin, or different cutoff values (p > 0.05 for all). A strong recommendation for serum VEGF-D determination to aid in the diagnosis of LAM was made according to the GRADE. Conclusions: VEGF-D seems to have great potential implications for the diagnosis of LAM in clinical practice due to its excellent specificity and suboptimal sensitivity.
Purpose: Breast cancer is the most frequently diagnosed cancer and is the leading cause of cancer-associated mortality in women worldwide. Intermedin (IMD) is an endogenous peptide that belongs to the calcitonin gene-related peptide family and has been reported to play important roles in several types of cancers, including breast cancer. In this study, we sought to investigate how IMD affects the behavior of breast cancer cells, the underlying mechanism of these effects, and whether blockade of IMD has a therapeutic effect against breast cancer. Methods: Transcriptome sequencing (RNA-Seq), cell biological experiments, Western blotting (WB), immunoprecipitation (IP), and animal tumor models were used. Results: IMD expression was significantly increased in breast cancer samples, and the IMD level was positively correlated with lymph node metastasis and Ki67 expression. Cell biological experiments showed that IMD promoted the anchorage-independent growth, migration, and invasive ability of breast cancer cells. Inhibiting IMD activity with an anti-IMD monoclonal antibody blocked these tumor-promoting effects. In addition, blockade of IMD reduced in situ tumor growth and significantly decreased lung metastasis of 4T1 breast cancer in vivo. IMD induced Src kinase phosphorylation, which triggered the transcription of c-Myc, a major oncoprotein controlling the expression of genes that encode ribosomal components. Our data suggest that IMD is involved in breast cancer cell invasion and metastasis, potentially through increasing ribosome biogenesis and protein translation via the Src/c-Myc signaling pathway. Conclusion : These results suggest that IMD may be a novel target for the treatment of breast cancer.
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