Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets.

BACKGROUND: The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. METHODS: The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and Fe2+ in both serum and synovium. RESULTS: JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and Fe2+ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. CONCLUSIONS: The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis.

The independent and combined effects of dietary and sleep patterns on the risk of metabolic dysfunction-associated fatty liver disease: a population-based cohort study.

Background & aims: accumulating evidence shows that various sleep behaviors are related to metabolic dysfunction-associated fatty liver disease (MAFLD), and that diet plays an important role in both preventing and treating this condition. However, the overall effect of a healthy sleep pattern and its joint effect with diet on the risk of MAFLD remain unclear. The aim of this study is to explore the independent and combined effects of dietary and sleep patterns on the MAFLD risk. Methods: this population-based prospective cohort study was conducted in China with a sample size of 13 687 participants. MAFLD was diagnosed through abdominal ultrasound and international expert consensus. Five healthy sleep behaviors were identified to create a healthy sleep pattern, while factor analysis was used to determine dietary patterns. Cox proportional hazards regression was utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: during a total of 49 912 person-years of follow-up, 2977 new cases of MAFLD were identified. The adjusted HRs (95% CIs) of MAFLD in relation to the healthy sleep pattern score were 0.87 (0.78-0.97), 0.83 (0.75-0.92), and 0.77 (0.68-0.87) for scores of 3, 4, and 5, respectively, compared to participants with the lowest score (0-2). A higher intake of animal food (adjusted HR4th quartile vs. 1st quartile, 1.15, 95% CI, 1.03-1.27) and a lower intake of vegetables (adjusted HR4th quartile vs. 1st quartile, 0.88, 95% CI, 0.78-0.99) were associated with a higher risk of MAFLD. Participants who adhered to both healthy dietary and sleep patterns had the lowest MAFLD risk compared to those who followed only one or neither of them. Conclusions: a healthy sleep pattern, especially in combination with a healthy diet, was associated with a lower risk of MAFLD. Future prevention strategies for MAFLD should include consideration of sleep behaviors, in addition to the current recommendations.

Waist-corrected BMI predicts incident diabetes mellitus in a population-based observational cohort study.

Introduction: Waist-corrected body mass index (wBMI), which combines BMI and waist circumference (WC) measurements, has proven superior to either measure alone for predicting obesity but has not yet been applied to the prediction of diabetes mellitus (DM). Methods: Over a 5-year period, 305,499 subjects were eligible for this study based on citizen health check-ups in the Tacheng Area of northwest China. Diagnosis of DM was defined as the end point. Results: After exclusion, a total of 111,851 subjects were included in the training cohort and 47,906 in the validation cohort. Participants of both sexes with wBMI in the upper quartiles had significantly higher incidence of DM than those with wBMI in the lower quartiles (log-rank χ2 = 236, p< 0.001 for men; log-rank χ2 = 304, p< 0.001 for women). After adjusting for multiple variables, WC, BMI, wBMI, and waist-to-height ratio (WHtR) were all independent predictors for diabetes. In men, the adjusted hazard ratios (HRs) of wBMI for diabetes for the second, third, and fourth quartiles were 1.297 [95% CI: 1.157, 1.455], 1.664 [95% CI: 1.493, 1.853], and 2.132 [95% CI: 1.921, 2.366], respectively, when compared with the first quartile. In women, they were 1.357 [95% CI: 1.191, 1.546], 1.715 [95% CI: 1.517, 1.939], and 2.262 [95% CI: 2.010, 2.545], respectively. Compared with WC, BMI, and WHtR, wBMI had the highest C-index in both men (0.679, 95% CI: 0.670, 0.688) and women (0.730, 95% CI: 0.722, 0.739). Finally, a nomogram was constructed to predict incident DM based on wBMI and other variables. In conclusion, wBMI had the strongest predictive capacity for incident DM when compared with WC, BMI, and WHtR, especially in women. Discussion: This study provides a reference for advanced investigation of wBMI on DM and other metabolic diseases in the future.

Associations between the serum triglyceride-glucose index and pericoronary adipose tissue attenuation and plaque features using dual-layer spectral detector computed tomography: a cross-sectional study.

Background and aims: The triglyceride-glucose (TyG) index is a reliable alternative marker for insulin resistance (IR). Pericoronary adipose tissue (PCAT) can indirectly reflect coronary inflammation. IR and coronary inflammation play a key role in the development and progression of coronary atherosclerosis. Therefore, this study investigated the relationships between the TyG index, PCAT and atherosclerotic plaque characteristics to explore whether IR might lead to coronary artery atherosclerosis progression by inducing coronary inflammation. Methods: We retrospectively collected data on patients with chest pain who underwent coronary computed tomography angiography using spectral detector computed tomography at our institution from June to December 2021. The patients were grouped based on their TyG index levels: T1 (low), T2 (medium), and T3 (high). Each patient was assessed for total plaque volume, plaque load, maximum stenosis, the plaque component volume proportion, high-risk plaques(HRPs), and plaque characteristics (including low attenuation plaques, positive remodeling, a napkin ring sign, and spot calcification). PCAT quantification was performed on the proximal right coronary artery using the fat attenuation index (FAI) measured from a conventional multicolor computed tomography image (FAI120kVp), a spectral virtual single-energy image (FAI40keV), and the slope of the spectral HU curve (λHU). Results: We enrolled 201 patients. The proportion of patients with maximum plaque stenosis, positive remodeling, low-density plaques, and HRPs increased as the TyG index level increased. Moreover, the FAI40keV and λHU significantly differed among the three groups, and we identified good positive correlations between FAI40keV and λHU and the TyG index (r = 0.319, P <0.01 and r = 0.325, P <0.01, respectively). FAI120kVp did not significantly differ among the groups. FAI40keV had the highest area under the curve, with an optimal cutoff value of -130.5 HU for predicting a TyG index value of ≥9.13. The multivariate linear regression analysis demonstrated that FAI40keV and λHU were independently positively related to a high TyG index level (standardized regression coefficients: 0.117 [P <0.001] and 0.134 [P <0.001], respectively). Conclusions: Patients with chest pain and a higher TyG index level were more likely to have severe stenosis and HRPs. Moreover, FAI40keV and λHU had good correlations with the serum TyG index, which may noninvasively reflect PCAT inflammation under insulin resistance. These results could help explain the mechanism of plaque progression and instability in patients with insulin resistance might be related to IR-induced coronary inflammation.

Prevalence of Diabetes in Patients with Hyperuricemia and Gout: A Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: To perform a systematic review and meta-analysis of the prevalence of diabetes in patients with hyperuricemia and gout. RECENT FINDINGS: Previous studies have confirmed that hyperuricemia and gout are associated with an increased risk of diabetes. A previous meta-analysis indicated that the prevalence of diabetes in patients with gout is 16%. Thirty-eight studies (458,256 patients) were included in the meta-analysis. The combined prevalence of diabetes among patients with hyperuricemia and gout were 19.10% (95% confidence interval [CI]: 17.60-20.60; I2 = 99.40%) and 16.70% (95% CI: 15.10-18.30; I2 = 99.30%), respectively. Patients from North America showed a higher prevalence of diabetes (hyperuricemia: 20.70% [95% CI: 16.80-24.60], gout: 20.70% [95% CI: 16.80-24.60]) than those from other continents. Older patients with hyperuricemia and those using diuretics showed a higher prevalence of diabetes than younger patients and those who were not using diuretics. Studies with a small sample size, case-control design, and low quality score had a higher prevalence of diabetes than studies with a large sample size, other designs, and a high quality score. The prevalence of diabetes among patients with hyperuricemia and gout is high. Controlling plasma glucose and uric acid levels of patients with hyperuricemia and gout is critical for the prevention of diabetes.

Dairy product consumption was associated with a lower likelihood of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. Several epidemiological studies attempted to assess the association between dairy product and the likelihood of NAFLD, but the contribution of dairy consumption to NAFLD remains controversial. We conducted a meta-analysis to investigate the association between dairy product consumption and NAFLD. Methods: We conducted a literature search using the PubMed, Web of Science and Scopus databases, we conducted a thorough search of the literature published before January 5, 2023. Combined odds ratios (ORs) and 95% confidence intervals (CIs) of NAFLD in relation to dairy product intake were estimated using random-effects models. Subgroup analysis and meta-regression were performed according to the study design, region, sex, body mass index (BMI), type of exposure, NAFLD diagnostic criteria, and exposure assessment tools. Results: We initially identified 4,634 relevant studies, of which 25 complied with the inclusion criteria, including seven cross-sectional studies, six case-control studies and one cohort study. A total of 51,476 participants (14,546 patients with NAFLD) were included in the meta-analysis. There was an inverse association between dairy product consumption and NAFLD (OR = 0.97, 95% CI = 0.94-0.99). Subgroup analysis demonstrated that lower likelihood of NAFLD was associated with dairy product consumption in subgroups of Asian populations, women, patients diagnosed using NAFLD-related scores, patients with a BMI of 18.5-24.9 kg/m2, dairy intake assessed using a food frequency questionnaire, milk consumption, and yogurt consumption. No noteworthy connection was observed in the other subgroups. Conclusion: Our meta-analysis findings revealed that dairy product consumption is inversely associated with NAFLD. Consumption of dairy products could help prevent the development of non-alcoholic fatty liver disease.

Associations between dietary patterns and nephrolithiasis risk in a large Chinese cohort: is a balanced or plant-based diet better?

Purpose: Individual food items and nutrients are associated with the development of nephrolithiasis. Few studies have investigated the association between dietary patterns, particularly plant-based diets, and this disease. We aim to explore the associations between dietary patterns and incident nephrolithiasis risk. Materials and methods: This prospective cohort study included 26 490 participants. Factor analysis was applied to dietary information to identify three a posteriori dietary patterns, and six a priori plant-based dietary patterns (overall plant-based diet index [PDI], healthful plant-based diet index [hPDI], unhealthful plant-based diet index [uPDI], vegan diet, lacto-ovo-vegetarian diet, and fish-vegetarian diet) were defined. Nephrolithiasis was diagnosed using ultrasonography. Cox proportional hazard regression models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident nephrolithiasis related to dietary patterns. Results: After 101 094 person-years follow-up, we documented 806 incident nephrolithiasis cases. An a posteriori balanced dietary pattern characterized by a higher intake of vegetables, eggs, grains, legumes, legume products, and meat was associated with a lower risk of nephrolithiasis (P for trend = 0.02). Compared to the reference group in the lowest quartile of the balanced pattern, participants in the highest quartile had an adjusted HR (95% CI) of 0.72 (0.53-0.96) for incident nephrolithiasis. Adherence to the uPDI increased the risk of incident nephrolithiasis (P for trend < 0.01; adjusted HR4th quartile vs. 1st quartile, 1.46, 95% CI, 1.14-1.97). No significant association was found between other a posteriori or a priori dietary patterns and incident nephrolithiasis. Conclusions: Adherence to a balanced dietary pattern, but not a plant-based diet, was associated with a lower nephrolithiasis risk. Moreover, higher uPDI consumption increased incident nephrolithiasis risk.

Trends in ethnic disparities in clinical cardiovascular health among Chinese adults from 2016-2020.

BACKGROUND AND AIMS: Little is known about the long-term trends in ethnic differences in cardiovascular health (CVH) in China in recent years. This study aimed to investigate ethnic differences in CVH and identify long-term trends in China. METHODS AND RESULTS: This survey was based on the physical examination data of Tacheng Prefecture in China from 2016 to 2020, and included 1,947,938 physical examination participants aged over 20 years for analysis. The American Heart Association (AHA) criteria were used to evaluate the clinical CVH of the subjects. The time trends from 2016 to 2020 were assessed using a weighted linear regression model stratified by ethnicity. The ethnic groups included Han, Kazakh, Hui, Mongolian, Uyghur, among others. The mean ideal clinical cardiovascular score was highest in Hui and lowest in Uyghur. The scores increased from 5.99 (5.95-6.03) to 6.11 (6.08-6.14) in Kazakh males and from 6.05 (5.99-6.11) to 6.11 (6.06-6.16) in Hui males among participants (Plinear trend < 0.001). The scores for the other groups declined significantly from 2016 to 2020(Plinear trend ＜ 0.05). In the sensitivity analysis, the trend remained unchanged after calculating the body mass index (BMI) cut-off for China. CONCLUSION: Clinical CVH differences still exist among different ethnic groups, with a decline in CVH from 2016 to 2020 in all except Kazakh and Hui males. This may indicate a higher incidence and poorer prognosis of cardiovascular disease in the future and can provide guidelines for improving CVH.

Glycated albumin indicates peripheral diabetic neuropathy.

AIMS: We investigated associations between serum levels of glycated albumin (GA) and glycated hemoglobin (HbA1c) and the presence of diabetic peripheral neuropathy (DPN) in patients with type 1 diabetes mellitus (T1DM). METHODS: Between September 2009 and April 2015, we evaluated 314 patients with T1DM in the Endocrinology Department of Shengjing Hospital of China Medical University. We divided the patients into the DPN group (n = 72) and the non-DPN group (n = 242), on the basis of the presence of DPN. RESULTS: The DPN group had significantly higher GA values than the non-DPN group. After univariate logistic regression, we selected several factors for further analysis: HbA1c, GA, duration of T1DM, body mass index, smoking, hypertension, and the presence of diabetic complications, including nephropathy, retinopathy, and cardiovascular disease. We performed a multivariate logistic regression analysis to examine the association between the presence of DPN and each of these variables. We identified GA, HbA1c, hypertension, smoking, retinopathy, and cardiovascular disease as independent variables for indicating the presence of DPN. Results of a receiver operating characteristic curve analysis revealed that the area under the curve of GA (0.771) was larger than that of HbA1c (0.629). We defined the cutoff value of GA as 23.5 % (sensitivity 0.764, specificity 0.661) and the cutoff value of HbA1c as 8.45 % (sensitivity 0.667, specificity 0.595) for predicting DPN in patients with T1DM. CONCLUSIONS: GA may be a better indicative marker of DPN in patients with T1DM than HbA1c.