Background
Diabetic kidney disease (DKD) is a common microvascular complication of diabetes mellitus (DM), which is the main cause of end-stage renal disease and renal replacement therapy. In recent years, more and more studies have described the immune-related mechanisms of kidney injury such as inflammation. But anti-inflammatory therapies are difficult to gain effect.
Methods
To explore immune-related mechanisms of DKD, we compared it with immune-related kidney diseases using bioinformatics analysis. We searched for DKD and membranous nephropathy (MN), IgA nephropathy (IgAN), lupus nephritis (LN) and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) in Gene Expression Omnibus (GEO) database. We downloaded RNA sequences and patient information for these five kidney diseases. We used Metascape software to analyze the enrichment of differentially expressed genes (DEGs) and shared genes in these diseases. By drawing the protein-protein interaction (PPI) network map, we screened out the hub genes, and used receiver operating characteristics (ROC) curve to perform diagnostic tests.
Results
We found that DKD shares 66 pathways with MN, 9 pathways with IgAN, 85 pathways with LN, and 54 pathways with AAV. Among them, the number of up-regulated pathways shared in the glomeruli was the largest. These pathways were mainly immune related pathways such as inflammation. We further analyzed the shared genes between DKD and LN or AAV, and found that the hub genes were C1QA, C1QB, C1R and C1S. These genes are associated with complement activation. Moreover, compared with healthy controls, their abnormal expression levels have diagnostic significance for DKD. At last, we used a network meta-analysis to confirm that current anti-inflammatory therapy is difficult to effectively treat DKD.
Conclusions
This study suggests that although there may be an immunological cause of renal injury in DKD, complement activation plays the key role in the occurrence and development of DKD. This would provide potential targets for novel therapies of DKD.
In 2017, China made an ambitious statement of high-quality development (HQD) with which to realize the goals of sustainability proposed by the United Nations. Our paper sheds new light on how the corporate high-quality development is affected by the responsibility system for environmental protection targets using a sample of energy-intensive firms from 2003 to 2018. We calculate the indexes for corporate high-quality development using entropy weighting for the five dimensions: efficiency, innovation, openness, greenness, and social responsibility. Then, we develop a difference-in-differences model to reveal that the responsibility system for environmental protection targets significantly dampens high-quality development of corporations, as the estimated coefficient is −0.0420 with a t-statistic of −2.9384. In contrast with private firms, the high-quality development of state-owned firms shows no significant correlation with environmental policy constraints. The efficiency of capital allocation by corporations mediates the effects of responsibility for environmental protection targets on high-quality development. Our study suggests several policy implications: first, understand the connotation of a high-quality development system, and formulate diversified regulatory policies. Second, the responsibility system for environmental protection targets in China should be implemented steadily within the firm’s abilities. Next, the high-quality development of private firms should generate great attention. Finally, corporate internal governance should be designed to improve high-quality development.
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