BackgroundTuberculosis (TB) always runs in the forefront of the global burden when it comes to infectious diseases. Tuberculosis, which can lead to impairment of quality of life, financial hardship, discrimination, marginalization, and social barriers, is a major public health problem. The assessment of TB burden and trend can provide crucial information for policy decision and planning, and help countries in the world to achieve the goal of sustainable development of ending the epidemic of TB in 2030.MethodsAll data are from the Global Burden of Disease 2019 (GBD 2019) database, which analyzed the burden trend of age-standardized incidence, DALYs, and deaths rate in TB and HIV/AIDS-infected TB over the past 30 years. Also, GBD 2019 not only analyzed the burden distribution of TB in 204 countries and main regions of the world but also analyzed the relationship between the burden of global TB and the socio–demographic Index (SDI).ResultsThe age-standardized incidence, age-standardized disability-adjusted life years (DALYs), and age-standardized deaths rate for HIV-negative TB were 10,671.45 (9,395.60–12,194.10), 59,042.45 (53,684.78–64,641.53), and 1,463.62 (1,339.24–1,602.71) (95% CI, per 100,000 person-years) in 2019, respectively. Age-standardized incidence, age-standardized DALYs, and age-standardized deaths rate of HIV/AIDS-XDR-TB (95% CI, per 1,000 person-years) were 2.10 (1.51–2.90), 64.23 (28.64–117.74), and 1.01 (0.42–1.86), respectively. We found that TB is inversely proportional to SDI, the age-standardized incidence, DALYs, and deaths rate low burden countries were in high SDI areas, while high burden countries were in low SDI areas. The global TB showed a slow decline trend, but the age-standardized incidence of HIV-positive TB was increasing, and mainly distributed in sub-Saharan Africa.ConclusionAge-standardized incidence, age-standardized DALYs, and age-standardized deaths rate of TB is related to SDI, and the burden of low SDI countries is lighter than that of high SDI countries. Without effective measures, it will be difficult for countries around the world to achieve the goal of ending the TB epidemic by 2030. Effective control of the spread of TB requires concerted efforts from all countries in the world, especially in the countries with low SDI, which need to improve the diagnosis and preventive measures of TB and improve the control of HIV/AIDS-TB.
Background. Keloid has brought great trouble to people and currently has no uniformly successful treatment. It is urgent to find new targets to effectively prevent the progress of keloid. The current research mainly identifies the differentially expressed genes (DEGs) in keloid through high-throughput sequencing technology and bioinformatics analysis technology, to screen new therapeutic targets and potential biomarkers. However, due to the different samples, different control groups, and small sample sizes, the sequencing results obtained from different studies are quite different and lack reliability. It is necessary to analyze the existing datasets in a reasonable way. Methods. Datasets about keloid were filtered in Gene Expression Omnibus (GEO) and ArrayExpress databases according to the inclusion and exclusion criteria. The discovery datasets were used for summarizing significant DEGs, and the validation datasets were to validate the mRNA and miRNA expression levels. The Encyclopedia of RNA Interactomes (ENCORI) online platform was used to predict the interactions between miRNAs and their target mRNAs. Protein-protein interaction network (PPI network) analysis and functional enrichment analysis were conducted. miRNA-mRNA network was established by Cytoscape software and verified in keloid tissue ( n = 8 ) by RT-qPCR. miR-29a-3p mimic and inhibitor were transfected into keloid fibroblasts (KFs) to preliminary verify its targets, the prognostic value of which was estimated by the receiver operating characteristic (ROC) curve. Results. A total of 6 datasets involving 20 patients were included. 15 miRNAs and 12 target mRNAs were identified as potential biomarkers for keloid patients. The RT-qPCR results showed that miR-29a-3p, miR-92a-3p, and miR-143-3p were downregulated, and all their target mRNAs were upregulated in keloid tissue ( P < 0.05 ). The expression of COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2 decreased when miR-29a-3p was overexpressed but increased when miR-29a-3p was knocked down ( P < 0.05 ). And these genes had a good performance in the diagnosis of keloid, especially when using keloid nonlesional skin or normal scar tissues as controls. Conclusion. The miRNA-mRNA network, especially miR-29a-3p and its targets, may provide insights into the underlying pathogenesis of keloid and serve as potential biomarkers for keloid treatment.
Background Burn patients are prone to infection as well as immunosuppression, which is a significant cause of death. Currently, there is a lack of prognostic biomarkers for immunosuppression in burn patients. This study was conducted to identify immune-related genes that are prognosis biomarkers in post-burn immunosuppression and potential targets for immunotherapy. Methods We downloaded the gene expression profiles and clinical data of 213 burn patients and 79 healthy samples from the Gene Expression Omnibus (GEO) database. Immune infiltration analysis was used to identify the proportion of circulating immune cells. Functional enrichment analyses were carried out to identify immune-related genes that were used to build miRNA-mRNA networks to screen key genes. Next, we carried out correlation analysis between immune cells and key genes that were then used to construct logistic regression models in GSE77791 and were validated in GSE19743. Finally, we determined the expression of key genes in burn patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results A total of 745 differently expressed genes were screened out: 299 were up-regulated and 446 were down-regulated. The number of Th-cells (CD4+) decreased while neutrophils increased in burn patients. The enrichment analysis showed that down-regulated genes were enriched in the T-cell activation pathway, while up-regulated genes were enriched in neutrophil activation response in burn patients. We screened out key genes (NFATC2, RORA, and CAMK4) that could be regulated by miRNA. The expression of key genes was related to the proportion of Th-cells (CD4+) and survival, and was an excellent predictor of prognosis in burns with an area under the curve (AUC) value of 0.945. Finally, we determined that NFATC2, RORA, and CAMK4 were down-regulated in burn patients. Conclusion We found that NFATC2, RORA, and CAMK4 were likely prognostic biomarkers in post-burn immunosuppression and potential immunotherapeutic targets to convert Th-cell dysfunction.
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