Background: Diabetes stands as a principal risk factor for severe complications including renal and cardiovascular diseases. The gradual rise in type 2 diabetes cases globally, coupled with a trend towards younger demographics, has led to an escalating prevalence of chronic kidney disease. However, its etiology is multifaceted, necessitating individualized treatment and refinement, particularly crucial in screening and managing the burden of CKDT2DM. A comprehensive analysis of CKD-T2DM burden at global, regional, and national levels from 2000 to 2019, based on the latest data, can inform screening, early diagnostics, and treatment strategies, thereby optimizing healthcare resource allocation. Methods: Utilizing data sourced from the Global Burden of Disease (GBD) database, we delineated the incidence, mortality, and DALYs rates of CKD-T2DM from 2000 to 2019 across global, regional, and national scales. We summarized the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and agestandardized death rate (ASDR) of CKD-T2DM globally, regionally, and nationally, presenting them visually. Moreover, we calculated and visually depicted the estimated annual percentage change (EAPC) of various CKDT2DM indicators at these levels. Additionally, CKD-T2DM patients were stratified by age to compare the age distribution of patient deaths and the age burden between 2000 and 2019. Findings: The disease burden of CKD-T2DM among young and middle-aged individuals globally has shown a sustained increase from 2000 to 2019. Incidence, mortality, and DALYs rates have exhibited an overall upward trend, with males showing higher rates compared to females. Significant disparities exist among different countries and regions, with India, China, and Mexico emerging as the countries with the highest number of new cases. Nicaragua, Mexico, and the United Arab Emirates have the highest age-standardized incidence rates, whereas Uganda, Ethiopia, and Burundi have the lowest. At the age level, the burden of CKD-T2DM exhibits varying trends among different age groups but generally shows an upward trajectory, particularly in the 45-49 age bracket. High systolic blood pressure and high BMI stand as the primary contributing factors to mortality and DALYs, with variations in their influence observed across different regions and levels of development. Interpretation: ver the past 20 years, the burden of CKD-T2DM among young and middle-aged individuals globally has continued to increase, with disparities existing among different countries, regions, and age groups, but overall showing an upward trend. The reasons for this trend are multifaceted, including global lifestyle changes such as dietary shifts, sedentary lifestyles, obesity, as well as population aging and inadequate preventive measures in certain regions. Addressing these challenges necessitates optimizing screening methods, adjusting lifestyles, enhancing management strategies, improving medical care and awareness levels, particularly intensifying awareness and screening efforts among males, reinforcing prevention and control measures for the 45-49

Hashimoto’s thyroiditis (HT) is a prevalent autoimmune thyroid disease, necessitating further research to identify effective treatment strategies. Two key pathophysiological factors of HT are inflammation and oxidative stress. Petunidin (PET) is an anthocyanin with anti-inflammatory and antioxidant properties. This study aimed to investigate the effect and mechanism of PET on HT. C57BL/6N mice were injected with thyroglobulin emulsified with adjuvant to establish the HT animal model. Our results showed that PET administration decreased the concentrations of TPOAb, TgAb, T3, T4, IgG, IgA and IgM in HT mice, accompanied by significant alterations in follicle shape and increased lymphocyte infiltrations. Additionally, the apoptosis rate, ROS level, MDA content, CD4+ level, IFN-γ and IL-17A levels, as well as the concentrations of IFN-γ and IL-17, were elevated in HT mice and reduced by PET treatment. Furthermore, HT patients exhibited higher levels of NOX4 and PKM2, which were positively correlated with TPOAb, IFN-γ, and IL-17 concentrations. In HT mice, PET therapy decreased the expression of PKM2 and NOX4 proteins. In summary, PET can improve thyroid dysfunction by suppressing apoptosis, oxidative stress and Th1/Th17 differentiation through regulation of the NOX4/PKM2 axis in HT mice, suggesting its promising potential for HT intervention

This research attempts to explore a simple and sensitive colorimetric method to detect metformin by using synthesized gold nanoparticles (AuNPs). Spherical AuNPs were synthesized by reducing HAuCl4 with EDTA. Transmission electron microscopy (TEM) and Zeta potential were used to observe AuNPs size and solution stability before and after the addition of metformin. AuNPs became unstable and aggregated after the addition of metformin, and the absorption peak changed from 520 to 654 nm after adding metformin. NaCl concentration is an important factor in AuNPs aggregation, as low as 70 nM metformin can induce the aggregation of AuNPs under 40 mM NaCl. The linear relationship of metformin detecting was gained in the range of 150 nM similar to 500 nM (R-2=0.955). The application of this method to the detection of metformin in actual samples has been verified. Therefore, AuNPs is considered to be a potential multidrug detection tool based on AuNPs surface modifiers.

Background: There are many patients, who start with the symptoms of ketosis or ketoacidosis, but their clinical and genetic characteristics are distinct. In this research, we studied the clinical, immune, and genetic characteristics of ketosis-onset diabetes, and the relationship between the clinical characteristics, anti-aminoacyl-tRNA synthetase antibody, and microRNAs. Methods: To study the clinical characteristics, 200 patients with newly onset diabetes mellitus along with ketosis or ketoacidosis were randomly selected. The male population in this study was 60.9%, with ages ranging from 7 to 72 years old, where 27% of the patients’ body mass index was ≥ 25 kg/m2 and the average HbA1c was 10.4 ±1.81%. Simultaneously, 50 healthy people with similar age and gender were chosen as the control group. Patients were divided into four subgroups based on the existing autoimmune antibodies and the preservation of β-cell function. The expression of microRNA-191 (miRNA-191) and microRNA-342 (miRNA-342) in plasma was detected by quantitative fluorescence PCR. Results: The frequency of anti-histidyl-tRNA synthetase antibody in A+ β+ and A+ β- subgroups was significantly higher than that in the other subgroups. There were no significant differences in the concentration of the anti-glycyl-tRNA synthetase antibody between the groups, but the frequency was higher in the A+ subgroup. The expression of miRNA-191 and miRNA-342 in plasma was up-regulated compared to the normal control group. Conclusion: The anti-histidyl and anti-glycyl-tRNA synthetase antibodies can be used as immunological markers to distinguish the subgroups of ketosis-onset diabetes mellitus, where anti-histidyl-tRNA synthetase antibody was more significant, comparatively. The miRNA-191 and miRNA-342 in plasma are related to ketosis-onset diabetes and can be used as biomarkers to predict ketosis-onset diabetes in the future.

Preeclampsia (PE) is a common pregnancy-specific disorder associated with significant maternal and fetal morbidity and mortality worldwide.The present study was performed to investigate the role of a CXC chemokine interleukin-8 (IL-8), in the pathogenesis of PE. IL-8 expression levels were assessed in placental and serum samples from 160 pregnant women with PE (N = 68 severe, 92 mild) and 140 healthy donors.Results from enzyme-linked immunosorbent assay showed that the concentration of serum IL-8 in PE patients (180.27 ± 5.81 ng/L) was significantly higher than that in healthy controls (41.57 ± 5.67 ng/L). Patients with severe PE had even higher serum IL-8 levels. Similar messenger RNA and protein expression patterns of IL-8 in placental tissues were confirmed by quantitative real-time polymerase chain reaction and immunohistochemical assay (N = 30 each in the mild PE, severe PE, and control groups). In addition, single nucleotide polymorphisms of IL-8 gene were detected with polymerase chain reaction-restricted fragment length polymorphism/SSP. The frequency of IL-8-251A allele was significantly higher than that in controls (58.4% vs 48.9%, P < 0.05). The occurrence frequency of haplotype -353A/-251A/+678T (AAT) in PE subjects was 27.2% as compared to 21.9% in the control participants (P < 0.05).Our study reveals that IL-8 expression is positively associated with the severity of PE. Presence of haplotype AAT in pregnant women appears to be a risk factor for PE.

Objective. To compare clinical characteristics, immunological markers, and β-cell functions of 4 subgroups (“Aβ” classification system) of ketosis-onset diabetes and ketosis prone diabetes patients without known diabetes, presenting with ketosis or diabetic ketoacidosis (DKA) and admitted to our department from March 2011 to December 2011 in China, with 50 healthy persons as control group. Results. β-cell functional reserve was preserved in 63.52% of patients. In almost each subgroup (except A− β− subgroup of ketosis prone group), male patients were more than female ones. The age of the majority of patients in ketosis prone group was older than that of ketosis-onset group, except A− β− subgroup of ketosis prone group. The durations from the patient first time ketosis or DKA onset to admitting to the hospital have significant difference, which were much longer for the ketosis prone group except the A+ β+ subgroup. BMI has no significant difference among subgroups. FPG of ketosis prone group was lower than that of A− β+ subgroup and A+ β+ subgroup in ketosis-onset group. A− β− subgroup and A+ β+ subgroup of ketosis prone group have lower HbA1c than ketosis-onset group. Conclusions. Ketosis-onset diabetes and ketosis prone diabetes do not absolutely have the same clinical characteristics. Each subgroup shows different specialty.

Purpose Endothelial dysfunction underlies the pathogenesis of preeclampsia, but its mechanism has not yet been completely understood. In this study we have aimed to measure homocysteine (Hcy), asymmetric dimethylarginine (ADMA), and nitric oxide (NO) levels as endothelial dysfunction markers in preeclamptic women.Methods Control-case study with 62 preeclamptic patients and 30 controls without pregnancy complications was conducted. Plasma total Hcy, determined by capillary column gas chromatography/mass spectrometry (GC/MS), was correlated with serum ADMA (determined by liquid chromatography/tandem mass spectrometry using (13)C(6)-L-arginine as the internal standard) and NO (analyzed by GC/MS).Results There was a highly significant increase in the plasma concentration of homocysteine (P < 0.001) and ADMA (P < 0.001) and a highly significant decrease in the plasma concentration of nitric oxide (P < 0.001) among the preeclamptic patients. The differences were more significant between mild and severe preeclampsia, with and without eclampsia, with and without HELLP (hemolysis, elevated serum level of liver enzymes, and low platelets). In the combined patients and control groups a highly significant positive correlation was found between the plasma concentrations of homocysteine and ADMA (r = 0.853, P < 0.001). In addition, significant negative correlations were detected between the plasma concentrations of nitric oxide and the plasma concentration of homocysteine (r = -0.870, P < 0.001) and ADMA (r = -0.895, P < 0.001). These significant correlations were found to persist, even when they were restricted to the preeclamptic patients.Conclusions The homocysteine ADMA NO may be at least partly responsible for etiology in preeclampsia and could be regarded as markers for the severity of the disease. Therefore, L-arginine may represent a novel therapy for the treatment of preeclampsia.