Influencing Factors of Glycemic Variability in Type 1 Diabetes Patients

BackgroundThe prevalence of T1DM (type 1 diabetes) is increasing year by year, and its autoimmunity can easily lead to the destruction of pancreaticβcells and insulin deficiency, making blood glucose difficult to reach the target.ObjectiveTo investigate the influencing factors of glucose variability in patients with T1DM by using flash glucose monitoring system (FGMS) , and to provide basis for future clinical use of targeted hypoglycemic treatment.MethodsUsing convenience sampling method, 85 patients with T1DM admitted to the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from May 2019 to April 2020 were selected as the research objects. The gender, age, diabetesduration, marital status, education level, smoking history, drinking history and other general data to determine body mass index (BMI) , waist hip ratio (WHR) , blood pressure (BP) , glycosylated hemoglobin (HbA1c) , total cholesterol (TC) , total triglycerides (TG) , high-density lipoprotein cholesterol (HDL-C) , low-density lipoprotein cholesterol (HDL-C) , estimated glomerular filtration rate (eGFR) , and urinary albumin creatinine ratio (UACR) of patients were collected. According to whether the mean amplitude of glycemic excursions (MAGE) of patient is higher than the overall average value of 0.82 mmol/L, patients were divided into high blood glucose fluctuation group and low blood glucose fluctuation group. The scores of the Summary of Diabetes Self Care Activities (SDSCA) and the Diabetes Empowerment Scale-Short Form (DES-SF) were calculated. Multiple linear regression was used to analyze the influencing factors of blood glucose fluctuation.ResultsThere were statistically significant difference between two groups in age, diabetes duration, HbA1c, TG, UACR, MEAN, SD, TIR, DES-SF scores and SDSCA scores (P<0.05) . Multiple linear regression analysis showed that age was the influencing factor of MEAN (β=-0.272, P=0.019) , SD (β=-0.300, P=0.009) , and MAGE (β=-0.254, P=0.007) , diabetes durationwas the influencing factor of MEAN (β=0.466, P=0.029) , HbA1cwas the influencing factor of MEAN (β=0.416, P<0.001) , SD (β=0.330, P=0.004) , TIR (β=-0.287, P=0.014) , MAGE (β=0.182, P<0.001) , UACR was the influencing factor of SD (β=0.264, P=0.040) , TIR (β=-0.350, P=0.006) , MAGE (β=0.236, P=0.009) , the total score of SDSCA was the influencing factor of MEAN (β=0.416, P<0.001) , SD (β=0.330, P=0.004) and TIR (β=-0.287, P=0.014) , the total score of DES-SF was the influencing factor of MEAN (β=-0.271, P=0.045) and TIR (β=0.865, P=0.016) .ConclusionAge, diabete duration, HbA1c, UACR, self-management behavior and self management potential were the influencing factors of glucose variability in patients with T1DM, individual hypoglycemic strategies should be formulated for patients according to these factors, so as to reduce patients' blood glucose fluctuations and delay the occurrence and development of the complications

Burden of liver cancer due to hepatitis C from 1990 to 2019 at the global, regional, and national levels

BackgroundLiver cancer due to hepatitis C (LCDHC) is one of the leading causes of cancer-related deaths worldwide, and the burden of LCDHC is increasing. We aimed to report the burden of LCDHC at the global, regional, and national levels in 204 countries from 1990 to 2019, stratified by etiology, sex, age, and Sociodemographic Index.MethodsData on LCDHC were available from the Global Burden of Disease, Injuries, and Risk Factors (GBD) study 2019. Numbers and age-standardized mortality, incidence, and disability-adjusted life year (DALY) rates per 100,000 population were estimated through a systematic analysis of modeled data from the GBD 2019 study. The trends in the LCDHC burden were assessed using the annual percentage change.ResultsGlobally, in 2019, there were 152,225 new cases, 141,810 deaths, and 2,878,024 DALYs due to LCDHC. From 1990 to 2019, the number of incidences, mortality, and DALY cases increased by 80.68%, 67.50%, and 37.20%, respectively. However, the age-standardized incidence, mortality, and DALY rate had a decreasing trend during this period. In 2019, the highest age-standardized incidence rates (ASIRs) of LCDHC were found in high-income Asia Pacific, North Africa and the Middle East, and Central Asia. At the regional level, Mongolia, Egypt, and Japan had the three highest ASIRs in 2019. The incidence rates of LCDHC were higher in men and increased with age, with a peak incidence in the 95+ age group for women and the 85–89 age group for men in 2019. A nonlinear association was found between the age-standardized rates of LCDHC and sociodemographic index values at the regional and national levels.ConclusionsAlthough the age-standardized rates of LCDHC have decreased, the absolute numbers of incident cases, deaths, and DALYs have increased, indicating that LCDHC remains a significant global burden. In addition, the burden of LCDHC varies geographically. Male and older adult/s individuals have a higher burden of LCDHC. Our findings provide insight into the global burden trend of LCDHC. Policymakers should establish appropriate methods to achieve the HCV elimination target by 2030 and reducing the burden of LCDHC

Identification and validation of potential diagnostic signature and immune cell infiltration for HIRI based on cuproptosis-related genes through bioinformatics analysis and machine learning

Background and aimsCuproptosis has emerged as a significant contributor in the progression of various diseases. This study aimed to assess the potential impact of cuproptosis-related genes (CRGs) on the development of hepatic ischemia and reperfusion injury (HIRI).MethodsThe datasets related to HIRI were sourced from the Gene Expression Omnibus database. The comparative analysis of differential gene expression involving CRGs was performed between HIRI and normal liver samples. Correlation analysis, function enrichment analyses, and protein-protein interactions were employed to understand the interactions and roles of these genes. Machine learning techniques were used to identify hub genes. Additionally, differences in immune cell infiltration between HIRI patients and controls were analyzed. Quantitative real-time PCR and western blotting were used to verify the expression of the hub genes.ResultsSeventy-five HIRI and 80 control samples from three databases were included in the bioinformatics analysis. Three hub CRGs (NLRP3, ATP7B and NFE2L2) were identified using three machine learning models. Diagnostic accuracy was assessed using a receiver operating characteristic (ROC) curve for the hub genes, which yielded an area under the ROC curve (AUC) of 0.832. Remarkably, in the validation datasets GSE15480 and GSE228782, the three hub genes had AUC reached 0.904. Additional analyses, including nomograms, decision curves, and calibration curves, supported their predictive power for diagnosis. Enrichment analyses indicated the involvement of these genes in multiple pathways associated with HIRI progression. Comparative assessments using CIBERSORT and gene set enrichment analysis suggested elevated expression of these hub genes in activated dendritic cells, neutrophils, activated CD4 memory T cells, and activated mast cells in HIRI samples versus controls. A ceRNA network underscored a complex regulatory interplay among genes. The genes mRNA and protein levels were also verified in HIRI-affected mouse liver tissues.ConclusionOur findings have provided a comprehensive understanding of the association between cuproptosis and HIRI, establishing a promising diagnostic pattern and identifying latent therapeutic targets for HIRI treatment. Additionally, our study offers novel insights to delve deeper into the underlying mechanisms of HIRI

Cpg-ODN, a TLR9 Agonist, Aggravates Myocardial Ischemia/Reperfusion Injury by Activation of TLR9-P38 MAPK Signaling

Background/Aims: Toll-like receptors (TLRs) have been implicated in myocardial ischemia/ reperfusion (I/R) injury. We examined the effect of CpG-oligodeoxynucleotide (ODN) on myocardial I/R injury. Methods: Male Sprague-Dawley rats were treated with either CpG-ODN or control ODN 1 h prior to myocardial ischemia (30 min) followed by reperfusion. Rats treated with phosphate-buffered saline (PBS) served as I/R controls (n = 8/group). Infarct size was determined by 2,3,5-triphenyltetrazolium chloride and Evans blue straining. Cardiac function was examined by echocardiography before and up to 14 days after myocardial I/R. Results: CpG-ODN administration significantly increased infarct size and reduced cardiac function and survival rate after myocardial I/R, compared to the PBS-treated I/R group. Control-ODN did not alter I/R-induced myocardial infarct size, cardiac dysfunction, and survival rate. Additionally, CpG-ODN promoted I/R-induced myocardial apoptosis and cleaved caspase-3 levels in the myocardium. CpG-ODN increased TLR9 activation and p38 phosphorylation in the myocardium. In vitro data also suggested that CpG-ODN treatment induced TLR9 activation and p38 phosphorylation. Importantly, p38 mitogen-activated protein kinase (MAPK) inhibition abolished CpG-ODN-induced cardiac injury. Conclusion: CpG-ODN, the TLR9 ligand, accelerates myocardial I/R injury. The mechanisms involve activation of the TLR9-p38 MAPK signaling pathway

Identification and validation of potential diagnostic signature and immune cell infiltration for NAFLD based on cuproptosis-related genes by bioinformatics analysis and machine learning

Background and aimsCuproptosis has been identified as a key player in the development of several diseases. In this study, we investigate the potential role of cuproptosis-related genes in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).MethodThe gene expression profiles of NAFLD were obtained from the Gene Expression Omnibus database. Differential expression of cuproptosis-related genes (CRGs) were determined between NAFLD and normal tissues. Protein–protein interaction, correlation, and function enrichment analyses were performed. Machine learning was used to identify hub genes. Immune infiltration was analyzed in both NAFLD patients and controls. Quantitative real-time PCR was employed to validate the expression of hub genes.ResultsFour datasets containing 115 NAFLD and 106 control samples were included for bioinformatics analysis. Three hub CRGs (NFE2L2, DLD, and POLD1) were identified through the intersection of three machine learning algorithms. The receiver operating characteristic curve was plotted based on these three marker genes, and the area under the curve (AUC) value was 0.704. In the external GSE135251 dataset, the AUC value of the three key genes was as high as 0.970. Further nomogram, decision curve, calibration curve analyses also confirmed the diagnostic predictive efficacy. Gene set enrichment analysis and gene set variation analysis showed these three marker genes involved in multiple pathways that are related to the progression of NAFLD. CIBERSORT and single-sample gene set enrichment analysis indicated that their expression levels in macrophages, mast cells, NK cells, Treg cells, resting dendritic cells, and tumor-infiltrating lymphocytes were higher in NAFLD compared with control liver samples. The ceRNA network demonstrated a complex regulatory relationship between the three hub genes. The mRNA level of these hub genes were further confirmed in a mouse NAFLD liver samples.ConclusionOur study comprehensively demonstrated the relationship between NAFLD and cuproptosis, developed a promising diagnostic model, and provided potential targets for NAFLD treatment and new insights for exploring the mechanism for NAFLD

Enhanced photovoltage in perovskite-type artificial superlattices on Si substrates

Abstract We have fabricated a three-component perovskite-type superlattice (SL) consisting of La 0.9 Sr 0.1 MnO 3 , SrTiO 3 and LaAlO 3 with atomic scale control by laser molecular beam epitaxy on Si substrates. When a He-Ne laser irradiated the superlattice by side illumination, a stable photovoltage was produced and the responsivity reached 46.7 mV mW −1 which is six times higher than that of a similarly grown La 0.9 Sr 0.1 MnO 3 single layer on Si substrates. This work demonstrates the potential of the present SL in photo-detectors operating at room temperature

E3 ubiquitin ligase CHIP facilitates Toll-like receptor signaling by recruiting and polyubiquitinating Src and atypical PKCζ

In mouse macrophages and dendritic cells, the CHIP E3 ubiquitin ligase is needed for transduction of signals initiated by TLR4 and TLR9 stimulation