Shared genetic architecture between type 2 diabetes and COVID-19 severity.

PURPOSE: Patients with type 2 diabetes (T2D) have demonstrated a higher risk for developing more severe cases of COVID-19, but the complex genetic mechanism between them is still unknown. The aim of the present study was to untangle this relationship using genetically based approaches. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D and COVID-19 severity, linkage disequilibrium score regression and Mendelian randomization (MR) analyses were utilized to quantify the genetic correlations and causal relationships between the two traits. Gene-based association and enrichment analysis were further applied to identify putative functional pathways shared between T2D and COVID-19 severity. RESULTS: Significant, moderate genetic correlations were detected between T2D and COVID-19 hospitalization (rg = 0.156, SE = 0.057, p = 0.005) or severe disease (rg = 0.155, SE = 0.057, p = 0.006). MR analysis did not support evidence for a causal effect of T2D on COVID-19 hospitalization (OR 1.030, 95% CI 0.979, 1.084, p = 0.259) or severe disease (OR 0.999, 95% CI 0.934, 1.069, p = 0.982). Genes having pgene < 0.05 for both T2D and COVID-19 severe were significantly enriched for biological pathways, such as response to type I interferon, glutathione derivative metabolic process and glutathione derivative biosynthetic process. CONCLUSIONS: Our findings further confirm the comorbidity of T2D and COVID-19 severity, but a non-causal impact of T2D on severe COVID-19. Shared genetically modulated molecular mechanisms underlying the co-occurrence of the two disorders are crucial for identifying therapeutic targets.

Relationship between the IL-4 gene promoter -590C/T (rs2243250) polymorphism and susceptibility to autoimmune diseases: a meta-analysis.

OBJECTIVE: Studies investigating the association between interleukin (IL)-4 gene promoter -590C/T (rs2243250) polymorphism and autoimmune diseases report conflicting results. To derive a more precise estimation of the relationship, a meta-analysis was performed. METHODS: A systematic literature search was conducted to identify relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to estimate the strength of association. RESULTS: A total of 6001 cases and 6788 controls from 24 studies were analysed. Significant association of the C allele of IL-4 rs2243250 polymorphism with rheumatoid arthritis (RA) was detected (odds ratio (OR) = 0.696, 95% confidence interval (CI) = 0.601-0.807). Stratification by ethnicity indicated an association between the IL-4 rs2243250 polymorphism and RA in Caucasians. Furthermore, the overall ORs of the associations between the C allele and multiple scleorosis (MS) were 1.340 (95% CI = 1.102-1.630). However, we failed to reveal any association between IL-4 rs2243250 polymorphism and systemic lupus erythematosus (SLE), type 1 diabetes (T1D) or Graves' disease (GD). CONCLUSIONS: The present study suggests that the IL-4 rs2243250 polymorphism might be associated with genetic susceptibility to autoimmune diseases, including RA and MS.

Lung, liver, prostate, bladder malignancies risk in systemic lupus erythematosus: evidence from a meta-analysis.

OBJECTIVE: The objective of this paper is to examine some solid tumors incidence in patients with systemic lupus erythematosus (SLE) derived from population-based cohort studies by means of meta-analysis. METHODS: Relevant electronic databases were searched for studies characterizing the associated risk of overall malignancy and four site-specific malignancies (lung, liver, prostate, bladder cancer) in patients with SLE. The meta-analysis procedure was used to pool standardized incidence rates (SIRs) with 95% confidence intervals (CIs) to evaluate the association. RESULTS: A total of seven cohort studies were identified, of which six provided the SIR for overall malignancy, seven reported the SIR for lung cancer, five for liver cancer, four for prostate cancer and six for bladder cancer. Overall, lung and liver cancers were more frequently observed in patients with SLE with SIR of 1.16 (95% CI = 1.12-1.21), 1.68 (95% CI = 1.33-2.13) and 2.44 (95% CI = 1.46-4.05), respectively. However, the risk of prostate cancer appeared to be somewhat reduced in male patients with SLE (SIR = 0.71, 95% CI = 0.57-0.89). CONCLUSIONS: This meta-analysis shows that SLE patients are at increased risk of developing cancer, particularly of the lung, bladder and liver. However, males with SLE have a decreased risk of prostate cancer.

[Non-linear compression for noises in non-contact vital signs detecting system].

A method for compressing the noises overlapping in the breath and heart signals of human beings, detected by the non-contact vital signs detecting system during the display of the waveforms in time domain, is discussed in this paper in detail. And what's more, the problem that the noise level is changed along with the increase of the gain of AD data-acquisition card and the display--gain of the software is solved by researching into the threshold of noise-level contraction in two types of circumstance in the lab, and the result of the breath and heart signal in the condition of lower noise is realized as well.

[The study on non-contact detection of breathing and heartbeat based on radar principles].

The paper introduces the design of hardware and software of non-contact detection system for breathing and heartbeat in human body with radar principles and technology. The detection technology is discussed. Under conditions of the illuminating power P < 1 mW and the distance S < 10 m, the non-contact breathing and heartbeat measurement, can be in different positions and with different clothing on the subject. The results show that the system with the technology has a high sensitivity, and is harmless to the health. It is a practicable non-contact detection technology for breathing and heartbeat of human body.

The role of oxidative stress in neuromelanin synthesis in PC12 cells.

Previous research has indicated that neuromelanin (NM) is involved in the pathogenesis of Parkinson's disease (PD). Increased reactive oxygen species (ROS) generation in PD sufferers is thought to be related to enhanced tyrosine hydroxylase (TH) activity and NM production. However, few reports have confirmed this hypothesis. In this study, PC12 cells of all experiments were exposed to 50 µmol/L levodopa (l-DOPA) to generate a model for NM synthesis. Meanwhile, PC12 cells were treated with glucose oxidase (GO) at different concentrations to generate oxidative stress. Finally, cell viability, TH activity, and NM generation in PC12 cells were measured. The results showed that GO dose-dependently stimulated oxidative stress generation in PC12 cells. Moderate increases in oxidative stress enhanced the viability of PC12 cells. However, an excessive level of oxidative stress can lead to the degeneration of PC12 cells. Notably, in the surviving PC12 cells, ROS significantly increased the TH activity, and the NM production was also upregulated. Thus, oxidative stress may upregulate the synthesis of NM, which may be a result of the increased TH activity observed in response to the elevated ROS in l-DOPA-treated PC12 cells.

Biological dose estimation for two severely exposed patients in a radiation accident in Shandong Jining, China, in 2004.

PURPOSE: To estimate the biological doses for two severely exposed subjects (A and B) in a radiation accident in Shandong Jining, China in 2004. MATERIALS AND METHODS: Conventional chromosome aberration analysis and cytokinesis-block micronuclei (CBMN) assay were performed in peripheral blood and bone marrow samples on two subjects after the accident. A new dose-effect curve and the nuclear division index (NDI) obtained from in vitro irradiation experiments using high dose of (60)Co gamma-rays were used to estimate the exposed doses. RESULTS: No metaphases or binucleated cells were observed in the peripheral blood cultures from either of the subjects. However, metaphases and binucleated cells were obtained from both subjects after bone marrow cultures. Both dicentric/ring and micronuclei yields were very high. The dose estimated for A and B were 20.0 Gy and 8.8 Gy, respectively, by dicentric/ring scoring, similar to the data by combination of the CBMN and NDI (CBMN + NDI) assay. The estimated doses by the two methods were in accordance with the clinical symptoms. CONCLUSION: The new curve, together with the CBMN + NDI assay, are reliable for estimating higher doses of irradiation. In future radiation accidents, the accuracy and significance of these methods can be further tested.