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Abstract Background A previous study demonstrated that N-glycosylation profiles of IgG are associated with subclinical atherosclerosis in a British population. However, the generalisability of this finding to other ethnic groups remains to be investigated, and it has yet to account for additional traditional atherosclerotic risk factors. The present study, thus, aims to explore IgG N-glycosylation profiles in Han Chinese with atherosclerosis, and their potential role in atherosclerosis, while controlling for traditional atherosclerotic risk factors. Methods Data of this case-control study were obtained from an established umbrella Health Examination Cohort Study (registration number: ChiCTR2100048740). The investigation was conducted at the Health Care Centre of the First Affiliated Hospital of Shantou University Medical College in China, from August 1, 2021, to July 31, 2022. A sample of 69 carotid atherosclerosis (CAS) cases was recruited from the umbrella cohort, along with 69 controls without carotid atherosclerosis, matched by traditional atherosclerosis-related risk factors, including gender, age, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia and obesity. Subsequently, serum IgG N-glycosylation was profiled using Ultra-Performance Liquid Chromatography. Results After propensity score matching, the relative abundance of IgG fucosylation in CAS cases was significantly lower than that in controls [95.32 (92.96, 95.99) vs. 95.96 (94.70, 96.58), P = 0.022]. The traditional atherosclerosis-related risk factors showed no statistically significant difference between CAS cases and controls (P > 0.05). Conclusions The reduced fucosylation of IgG in CAS cases underscores the pivotal role of afucosylation in CAS. Enhancing the inflammatory capability of IgG via initiating antibody-dependent cell-mediated cytotoxicity could be the potential mechanism behind this, which should be further verified by functional studies.

Circular RNAs (circRNAs) play a crucial role in cancer development and progression. This study aimed to identify potential circRNA biomarkers for osteosarcoma. Articles published from January 2010 to September 2023 were searched across eight databases to compare circRNA expression profiles in osteosarcoma and control samples (human, animal and cell lines). Meta-analysis was conducted under a random effects model. Subgroup analysis of circRNAs in different samples and tissues was performed. Diagnostic value was evaluated using receiver operator characteristic curves. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis explored functions of circRNA host genes. A circRNA-miRNA-mRNA axis depicted the regulatory mechanism in osteosarcoma. Among 1356 circRNAs with differential expression were identified across 226 original studies, only 74 were reported in at least three published sub-studies. Meta-analysis identified 58 dysregulated circRNAs (52 upregulated and 6 downregulated). Eleven circRNAs consistently showed dysregulation in tissues and cell lines, with hsa_circ_0005721 showing potential as a circulating biomarker in osteosarcoma. Sensitivity analysis demonstrated 97 % consistency. The overall area under the curve was 0.87 (95 % CI, 0.83–0.89). GO and KEGG enrichment analyses revealed host gene involvement in cancer. The circRNA-miRNA-mRNA axis revealed the regulatory axis and interactions within osteosarcoma specifically. This study demonstrates circRNAs as potential diagnostic biomarkers for osteosarcoma. Consistently reported dysregulated circRNAs are potential biomarkers in osteosarcoma pathogenesis, with hsa_circ_0005721 as a potential circulating biomarker for diagnosis and treatment.

Abstract Background Both elevated inflammation and atherogenic dyslipidemia are prominent in young-onset diabetes and are increasingly identified as biologically intertwined processes that contribute to diabetogenesis. We aimed to investigate the age-specific risks of type 2 diabetes (T2D) upon concomitant chronic inflammation and atherogenic dyslipidemia. Methods Age-stratified Cox regression analysis of the risk of incident diabetes upon co-exposure to time-averaged cumulative high-sensitivity C-reactive protein (CumCRP) and atherogenic index of plasma (CumAIP) among 42,925 nondiabetic participants from a real-world, prospective cohort (Kailuan Study). Results During a median 6.41 years of follow-up, 3987 T2D developed. Isolated CumAIP and CumCRP were significantly associated with incident T2D in the entire cohort and across all age subgroups. Both CumAIP and CumCRP were jointly associated with an increased risk of diabetes (P-interaction = 0.0126). Compared to CumAIP

Immunoglobulin G (IgG) is the most abundant plasma glycoprotein and a prominent humoral immune mediator. Glycan composition affects the affinity of IgG to ligands and consequent immune responses. The modification of IgG N-glycosylation is considered to be one of the various mechanisms by which sex hormones modulate the immune system. Although the menstrual cycle is the central sex hormone-related physiological process in most women of reproductive age, IgG N-glycosylation dynamics during the menstrual cycle have not yet been investigated. To fill this gap, we profiled the plasma IgG N-glycans of 70 healthy premenopausal women at 12 time points during their menstrual cycles (every 7 days for 3 months) using hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC). We observed cyclic periodic changes in the N-glycosylation of IgG in association with the menstrual cycle phase and sex hormone concentration in plasma. On the integrated cohort level, the modeled average menstrual cycle effect on the abundance of IgG N-glycosylation traits was low for each trait, with the highest being 1.1% for agalactosylated N-glycans. However, intrapersonal changes were relatively high in some cases; for example, the largest difference between the minimum and maximum values during the menstrual cycle was up to 21% for sialylated N-glycans. Across all measurements, the menstrual cycle phase could explain up to 0.72% of the variation in the abundance of a single IgG glycosylation trait of monogalactosylation. In contrast, up to 99% of the variation in the abundance of digalactosylation could be attributed to interpersonal differences in IgG N-glycosylation. In conclusion, the average extent of changes in the IgG N-glycopattern that occur during the menstrual cycle is small; thus, the IgG N-glycoprofiling of women in large sample-size studies can be performed regardless of menstrual cycle phase.

Although the association between immunoglobulin G (IgG) N-glycosylation and metabolic traits has been previously identified, the causal association between them remains unclear. In this work, we used Mendelian randomization (MR) analysis to integrate genome-wide association studies (GWASs) and quantitative trait loci (QTLs) data in order to investigate the bidirectional causal association of IgG N-glycosylation with metabolic traits. In the forward MR analysis, 59 (including nine putatively causal glycan peaks (GPs) for body mass index (BMI) (GP1, GP6, etc.) and seven for fasting plasma glucose (FPG) (GP1, GP5, etc.)) and 15 (including five putatively causal GPs for BMI (GP2, GP11, etc.) and four for FPG (GP1, GP10, etc.)) genetically determined IgG N-glycans were identified as being associated with metabolic traits in one- and two-sample MR studies, respectively, by integrating IgG N-glycan-QTL variants with GWAS results for metabolic traits (all P

Abstract Background Concurrent atherogenic dyslipidemia and elevated inflammation are commonly observed in overt hyperglycemia and have long been proposed to contribute to diabetogenesis. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident type 2 diabetes (T2D) remains unclear. Methods Longitudinal analysis of data on 52,224 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between high-sensitivity C-reactive protein (hsCRP) and the atherogenic index of plasma (AIP, calculated as triglyceride/high-density lipoprotein) in an approximately 4-year exposure period (2006/2007 to 2010/2011). After excluding 8824 participants with known diabetes, 43,360 nondiabetic participants were included for further analysis of the T2D outcome. Cox regression models were used to examine the adjusted hazard ratios (aHRs) upon the cumulative hsCRP (CumCRP) and AIP (CumAIP) in the exposure period. Results In temporal analysis, the adjusted standardized correlation coefficient (β1) of hsCRP_2006/2007 and AIP_2010/2011 was 0.0740 (95% CI, 0.0659 to 0.0820; P < 0.001), whereas the standardized correlation coefficient (β2) of AIP_2006/2007 and hsCRP_2010/2011 was − 0.0293 (95% CI, − 0.0385 to − 0.0201; P < 0.001), which was significantly less than β1 (P < 0.001). During a median follow-up of 7.9 years, 5,118 T2D cases occurred. Isolated exposure to CumAIP or CumCRP was dose-dependently associated with T2D risks, independent of traditional risk factors. Significant interactions were observed between the median CumAIP (− 0.0701) and CumCRP thresholds (1, 3 mg/L) (P = 0.0308). Compared to CumAIP < − 0.0701 and CumCRP < 1 mg/L, those in the same CumAIP stratum but with increasing CumCRP levels had an approximately 1.5-fold higher T2D risk; those in higher CumAIP stratum had significantly higher aHRs (95% CIs): 1.64 (1.45–1.86), 1.87 (1.68–2.09), and 2.04 (1.81–2.30), respectively, in the CumCRP < 1, 1 ≤ CumCRP < 3, CumCRP ≥ 3 mg/L strata. Additionally, the T2D risks in the co-exposure were more prominent in nonhypertensive, nondyslipidemic, nonprediabetic, or female participants. Conclusions These findings suggest a stronger association between elevated hsCRP and future AIP changes than vice versa and highlight the urgent need for combined assessment and management of chronic inflammation and atherogenic dyslipidemia in primary prevention, particularly for those with subclinical risks of T2D.

Abstract Background Immunoglobulin G (IgG) N-glycans have been shown to be associated with the risk of type 2 diabetes (T2D) and its risk factors. However, whether these associations reflect causal effects remain unclear. Furthermore, the associations of IgG N-glycans and inflammation are not fully understood. Methods We examined the causal associations of IgG N-glycans with inflammation (C-reactive protein (CRP) and fibrinogen) and T2D using two-sample Mendelian randomization (MR) analysis in East Asian and European populations. Genetic variants from IgG N-glycan quantitative trait loci (QTL) data were used as instrumental variables. Two-sample MR was conducted for IgG N-glycans with inflammation (75,391 and 18,348 participants of CRP and fibrinogen in the East Asian population, 204,402 participants of CRP in the European population) and T2D risk (77,418 cases and 356,122 controls of East Asian ancestry, 81,412 cases and 370,832 controls of European ancestry). Results After correcting for multiple testing, in the East Asian population, genetically determined IgG N-glycans were associated with a higher risk of T2D, the odds ratios (ORs) were 1.009 for T2D per 1- standard deviation (SD) higher GP5, 95% CI = 1.003–1.015; P = 0.0019; and 1.013 for T2D per 1-SD higher GP13, 95% CI = 1.006–1.021; P = 0.0005. In the European population, genetically determined decreased GP9 was associated with T2D (OR = 0.899 per 1-SD lower GP9, 95% CI: 0.845–0.957). In addition, there was suggestive evidence that genetically determined IgG N-glycans were associated with CRP in both East Asian and European populations after correcting for multiple testing, but no associations were found between IgG N-glycans and fibrinogen. There was limited evidence of heterogeneity and pleiotropy bias. Conclusions Our results provided novel genetic evidence that IgG N-glycans are causally associated with T2D.

Objectives Over the coming decades, China is expected to face the largest worldwide increase in dementia incidence. Mobile health (mHealth) may improve the accessibility of dementia prevention strategies, targeting lifestyle-related risk factors. Our aim is to explore the needs and views of Chinese older adults regarding healthy lifestyles to prevent cardiovascular disease (CVD) and dementia through mHealth, supporting the Prevention of Dementia using Mobile Phone Applications (PRODEMOS) study.Design Qualitative semi-structured interview study, using thematic analysis.Setting Primary and secondary care in Beijing and Tai’an, China.Participants Older adults aged 55 and over without dementia with an increased dementia risk, possessing a smartphone. Participants were recruited through seven hospitals participating in the PRODEMOS study, purposively sampled on age, sex, living area and history of CVD and diabetes.Results We performed 26 interviews with participants aged 55–86 years. Three main themes were identified: valuing a healthy lifestyle, sociocultural expectations and need for guidance. First, following a healthy lifestyle was generally deemed important. In addition to generic healthy behaviours, participants regarded certain specific Chinese lifestyle practices as important to prevent disease. Second, the sociocultural context played a crucial role, as an important motive to avoid disease was to limit the care burden put on family members. However, time-consuming family obligations and other social values could also impede healthy behaviours such as regular physical activity. Finally, there seemed to be a need for reliable and personalised lifestyle advice and for guidance from a health professional.Conclusions The Chinese older adults included in this study highly value a healthy lifestyle. They express a need for personalised lifestyle support in order to adopt healthy behaviours. Potentially, the PRODEMOS mHealth intervention can meet these needs through blended lifestyle support to improve risk factors for dementia and CVD.Trial registration number ISRCTN15986016; Pre-results.

Background Suboptimal Health Status Questionnaire-25 (SHSQ-25) is an established tool for measuring a precision health state between health and illness. The present study aims to assess the validity and reliability of a Persian version of SHSQ-25 (P-SHSQ-25) in a university staff Iranian population. Methods A sample of 316 academic and supporting staff (163 males, age range from 23 to 64 years old) from Hamadan University of Medical Sciences, Hamadan, Iran was recruited in this population-based cross-sectional study with a questionnaire validation from Apri1 to October 2022. Forward-backward translation method was performed for the SHSQ-25 translation from English to Persian. Internal reliability, content, convergence, discriminative and construct validity of the P-SHSQ-25 were examined. The factorial structure of the P-SHSQ-25 across groups was examined using measurement invariant test. Results In the translation process, the conceptual equivalence of the P-SHSQ-25 with the English version was confirmed. The item-content validity index and content validity ratio of all P-SHSQ-25 items were higher than the cut-off values of 0.70 and 0.62, respectively. Cronbach's a was higher than 0.70 for all P-SHSQ-25 domains. The confirmatory factor analysis (CFA) showed the fitness of five factors on the data set (comparative fit index = 0.88, and root mean square error of approximation = 0.07). The CFA model fit did not change substantially across sex, age, occupation, economic status, and body mass index (≥ comparative fit index (CFI)<0.01). Conclusions The P-SHSQ-25 can be used as a reliable and valid tool to measure health status for screening pre-chronic disease conditions in a primary care setting among Iranian population. [ABSTRACT FROM AUTHOR]