Search

Genome-wide association studies have identified 19p13.3 locus associated with primary biliary cholangitis (PBC). Here we aim to identify causative variant(s) and initiate efforts to define the mechanism by which the 19p13.3 locus variant(s) contributes to the pathogenesis of PBC. A genome-wide meta-analysis of 1931 PBC subjects and 7852 controls in two Han Chinese cohorts confirms the strong association between 19p13.3 locus and PBC. By integrating functional annotations, luciferase reporter assay and allele-specific chromatin immunoprecipitation, we prioritize rs2238574, an AT-Rich Interaction Domain 3A (ARID3A) intronic variant, as a potential causal variant at 19p13.3 locus. The risk allele of rs2238574 shows higher binding affinity of transcription factors, leading to an increased enhancer activity in myeloid cells. Genome-editing demonstrates the regulatory effect of rs2238574 on ARID3A expression through allele-specific enhancer activity. Furthermore, knock-down of ARID3A inhibits myeloid differentiation and activation pathway, and overexpression of the gene has the opposite effect. Finally, we find ARID3A expression and rs2238574 genotypes linked to disease severity in PBC. Our work provides several lines of evidence that a non-coding variant regulates ARID3A expression, presenting a mechanistic basis for association of 19p13.3 locus with the susceptibility to PBC.

Objective Liver damage is a common manifestation and can be life-threatening in adult-onset Still's disease (AOSD), an autoinflammatory disease. The hallmark of AOSD is activation of neutrophils, whose infiltration in liver is suspected to promote tissue injury. Here we aimed to identify a candidate biomarker and to validate its association with liver damage in AOSD. Methods Transcriptome analysis of neutrophils from treatment-naïve active AOSD patients and healthy donors was performed. Lipocalin-2 (LCN2) expression was assessed in neutrophils, plasma and liver biopsies of AOSD. The correlations of LCN2 with different variables and its ability to identify liver damage from AOSD patients were analysed. Results LCN2, a novel biomarker in hepatic inflammation, was found to be upregulated in AOSD neutrophils by RNA sequencing and confirmed at the mRNA and protein levels. Plasma levels of LCN2 were significantly higher in AOSD patients than healthy controls, RA and SLE patients. Plasma LCN2 levels were closely correlated with inflammatory markers, systemic score, HScore and cytokines. Moreover, LCN2 levels were increased in active AOSD with liver involvement and independently associated with liver dysfunction. Enhanced expression of LCN2 was detected in liver biopsies from three patients with ongoing liver injury. Furthermore, the area under the curve value of LCN2 for identifying AOSD with liver injury from other liver diseases was 0.9694. Conclusion Our results reveal that neutrophils-derived LCN2 is higher in plasma and liver tissue in AOSD patients than in healthy controls, and it could serve as a potent biomarker for identifying AOSD with systemic inflammation, especially liver damage caused by hyperinflammation. [ABSTRACT FROM AUTHOR]

Background: The concept of healthy aging has become a global health strategy in response to the population aging. In China, old-aged migrants are facing serious health care challenges due to the obstacles in the utilization of health services, social integration and ignored public policies. We aimed to examine the old-aged migrants' utilization of the essential public health services and its underlying factors on account of change of residence, and social support.Methods: Data came from the senior sample (aged over 65 years, n = 11 161) of the 2015 National Migrant Dynamic Monitoring Survey in China that employed Probability Proportionate to Size method as a sampling strategy. χ2 tests and binary multilevel model were conducted to analyze the difference and the underlying factors of the utilization of essential health services among old-aged migrants.Results: Approximately 66.2% of old-aged migrants did not receive free physician examination services from health institutions in the past year, and 34.6% of old-aged migrants with chronic disease have been followed up by doctors. There were significant differences in the utilization of essential public health services among old-aged migrants across different individuals and families. It showed that exercise time, migrating range, migrating reason, physical health condition, chronic disease, local friends, health insurance, household expenditure, and income were significantly associated with the elderly migrants' utilization of essential public health services.Conclusions: The utilization of essential public health services among old-aged migrants was insufficient in comparison with the general population. The government should launch targeted policies such as production and work-related injuries for the floating population. The supply side should promote the equalization of essential public health services for migrants. Social organizations and community should undertake the responsibility in social support for old-aged migrants. [ABSTRACT FROM AUTHOR]

The diabetic gastroparesis is one of most common complications of diabetic mellitus. The insufficient intake of calories and fluid may cause malnutrition, resulting in fluid and electrolyte imbalance. The occurrence of diabetic ketoacidosis is associated with glucose variation and imbalanced fluid and electrolyte, This paper reviewed the nursing management of a type 1 diabetic patient with diabetic gastroparesis. Key issues of nursing included correcting imbalances of fluid and electrolyte, individualized diet guidance and management of glucose variation. According to the malnutrition and characteristics of glucose variation, individualized nursing was carried out to improve the clinical symptoms and blood glucose control. [ABSTRACT FROM AUTHOR]