Visit-to-visit variability in triglyceride-glucose index and diabetes:A 9-year prospective study in the Kailuan Study

Instruction/Aims: It is unknown whether variability in the triglyceride-glucose index (TyG-index) is associated with the risk of diabetes. Here, we sought to characterize the relationship between TyG-index variability and incident diabetes. Methods: We performed a prospective study of 48,013 participants in the Kailuan Study who did not have diabetes. The TyG-index was calculated as ln [triglyceride (TG, mg/dL) concentration × fasting blood glucose concentration (FBG, mg/dL)/2]. The TyG-index variability was assessed using the standard deviation (SD) of three TyG-index values that were calculated during 2006/07, 2008/09, and 2010/11. We used the Cox proportional hazard models to analyze the effect of TyG-index variability on incident diabetes. Results: A total of 4,055 participants were newly diagnosed with diabetes during the study period of 8.95 years (95% confidence interval (CI) 8.48–9.29 years). After adjustment for confounding factors, participants in the highest and second-highest quartiles had significantly higher risks of new-onset diabetes versus the lowest quartile, with hazard ratios (95% CIs) of 1.18 (1.08–1.29) and 1.13 (1.03–1.24), respectively (P trend< 0.05). These higher risks remained after further adjustment for the baseline TyG-index. Conclusions: A substantial fluctuation in TyG-index is associated with a higher risk of diabetes in the Chinese population, implying that it is important to maintain a normal and consistent TyG-index

Dementia incidence trend in England and Wales, 2002–19, and projection for dementia burden to 2040: analysis of data from the English Longitudinal Study of Ageing

Background: Dementia incidence declined in many high-income countries in the 2000s, but evidence on the post-2010 trend is scarce. We aimed to analyse the temporal trend in England and Wales between 2002 and 2019, considering bias and non-linearity. // Methods: Population-based panel data representing adults aged 50 years and older from the English Longitudinal Study of Ageing were linked to the mortality register across wave 1 (2002–03) to wave 9 (2018–19) (90 073 person observations). Standard criteria based on cognitive and functional impairment were used to ascertain incident dementia. Crude incidence rates were determined in seven overlapping initially dementia-free subcohorts each followed up for 4 years (ie, 2002–06, 2004–08, 2006–10, 2008–12, 2010–14, 2012–16, and 2014–18). We examined the temporal trend of dementia incidence according to age, sex, and educational attainment. We estimated the trend of dementia incidence adjusted by age and sex with Cox proportional hazards and multistate models. Restricted cubic splines allowed for potential non-linearity in the time trend. A Markov model was used to project future dementia burden considering the estimated incidence trend. // Findings: Incidence rate standardised by age and sex declined from 2002 to 2010 (from 10·7 to 8·6 per 1000 person-years), then increased from 2010 to 2019 (from 8·6 to 11·3 per 1000 person-years). Adjusting for age and sex, and accounting for missing dementia cases due to death, estimated dementia incidence declined by 28·8% from 2002 to 2008 (incidence rate ratio 0·71, 95% CI 0·58–0·88), and increased by 25·2% from 2008 to 2016 (1·25, 1·03–1·54). The group with lower educational attainment had a smaller decline in dementia incidence from 2002 to 2008 and a greater increase after 2008. If the upward incidence trend continued, there would be 1·7 million (1·62–1·75) dementia cases in England and Wales by 2040, 70% more than previously forecast. // Interpretation: Dementia incidence might no longer be declining in England and Wales. If the upward trend since 2008 continues, along with population ageing, the burden on health and social care will be large. // Funding: UK Economic and Social Research Council

The occurrence of early atrial fibrillation after cardiac valve operation and the establishment of a nomogram model

BackgroundPostoperative atrial fibrillation (POAF) is a common complication after cardiac surgery, which is associated with age and massive bleeding. However, whether thyroid hormone (TH) level can affect POAF remains controversial.AimTo investigate the occurrence and risk factors of POAF, in particular, the preoperative TH level of patients was introduced into this study as a variable for analysis, and a column graph prediction model of POAF was constructed.MethodsPatients who underwent valve surgery in Fujian Cardiac Medical Center from January 2019 to May 2022 were retrospectively analyzed and divided into POAF group and NO-POAF group. Baseline characteristics and relevant clinical data were collected from the two groups of patients. Independent risk factors for POAF were screened using univariate analysis and binary logistic regression analysis, and a column line graph prediction model was established based on the regression analysis results, and the diagnostic efficacy and calibration of the model were evaluated using the Receiver Operating Characteristic Curve (ROC) and calibration curve.ResultsA total of 2,340 patients underwent valve surgery, excluding 1,751 patients, a total of 589 patients were included, including 89 patients in POAF group and 500 patients in NO-POAF group. The total incidence of POAF was 15.1%. The results of the Logistics regression analysis showed that gender, age, leukocytes and TSH were risk factors of POAF. The area under the ROC curve of the nomogram prediction model for POAF was 0.747 (95% CI: 0.688–0.806, P &lt; 0.001), with a sensitivity of 74.2% and specificity of 68%. Hosmer-Lemeshow test showed χ2 = 11.141, P = 0.194 &gt; 0.05, the calibration curve was well fitted.ConclusionThe results of this study show that gender, age, leukocyte and TSH are risk factors of POAF, and the nomogram prediction model has a good prediction effect. Due to the limited sample size and included population, more studies are needed to validate this result

Pulmonary infection associated with immune dysfunction is associated with poor prognosis in patients with myelodysplastic syndrome accompanied by TP53 abnormalities

The aim of this study was to examine the characteristics and prognosis of patients with myelodysplastic syndrome (MDS) accompanied by TP53 abnormalities and explore potential prognostic factors and treatment responses. This retrospective analysis included 95 patients with MDS and TP53 abnormalities and 173 patients with MDS without TP53 abnormalities at the Fujian Medical University Union Hospital between January 2016 and June 2023. Among patients with TP53 abnormalities, 26 (27.4%) developed AML during the disease course, with a median transformation time of 5.7 months. Complex karyotypes were observed in 73.1% of patients, and the proportions of -5 or del(5q), -7 or del(7q), +8, and -20 or del(20q) were 81.8%, 54.5%, 30.7%, and 25.0%, respectively. These patients exhibited poor survival, with a median overall survival (OS) of 7.3 months, and had 1- and 2-year OS rates of 42.2% and 21.5%, respectively. The complete response rates for azacitidine monotherapy, venetoclax combined with azacitidine, decitabine monotherapy, and decitabine combined with low-dose chemotherapy were 9.1%, 41.7%, 37.5%, and 33.3%, respectively. Long-term survival was similar among the four treatment groups. Patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) had a median OS of 21.3 months, which trended to be longer than that of patients who did not undergo allo-HSCT (5.6 months; P = 0.1449). Patients with pulmonary infection at diagnosis experienced worse OS than those without pulmonary infection (2.3 months vs. 15.4 months; P &lt; 0.0001). Moreover, 61.9% of patients with pulmonary infection had immune dysfunction, with a ratio of CD4+ to CD8+ T lymphocytes below two. Pulmonary infections and complex karyotypes were independent adverse prognostic factors for OS. In conclusion, TP53 abnormalities in patients with MDS were frequently accompanied by complex karyotypes, and treatments based on hypomethylating agents or venetoclax have limited efficacy. Pulmonary infections associated with immune dysfunction is associated with poor prognosis

Growing old in China in socioeconomic and epidemiological context: systematic review of social care policy for older people

BACKGROUND: From 2020 to 2050, China's population aged ≥65 years old is estimated to more than double from 172 million (12·0%) to 366 million (26·0%). Some 10 million have Alzheimer's disease and related dementias, to approach 40 million by 2050. Critically, the population is ageing fast while China is still a middle-income country. METHODS: Using official and population-level statistics, we summarise China's demographic and epidemiological trends relevant to ageing and health from 1970 to present, before examining key determinants of China's improving population health in a socioecological framework. We then explore how China is responding to the care needs of its older population by carrying out a systematic review to answer the question: 'what are the key policy challenges to China achieving an equitable nationwide long-term care system for older people?'. Databases were screened for records published between 1st June 2020 and 1st June 2022 in Mandarin Chinese or English, reflecting our focus on evidence published since introduction of China's second long-term care insurance pilot phase in 2020. RESULTS: Rapid economic development and improved access to education has led to widescale internal migration. Changing fertility policies and household structures also pose considerable challenges to the traditional family care model. To deal with increasing need, China has piloted 49 alternative long-term care insurance systems. Our findings from 42 studies (n = 16 in Mandarin) highlight significant challenges in the provision of quality and quantity of care which suits the preference of users, varying eligibility for long-term care insurance and an inequitable distribution of cost burden. Key recommendations include increasing salaries to attract and retain staff, introduction of mandatory financial contributions from employees and a unified standard of disability with regular assessment. Strengthening support for family caregivers and improving smart old age care capacity can also support preferences to age at home. CONCLUSIONS: China has yet to establish a sustainable funding mechanism, standardised eligibility criteria and a high-quality service delivery system. Its long-term care insurance pilot studies provide useful lessons for other middle-income countries facing similar challenges in terms of meeting the long-term care needs of their rapidly growing older populations

Anti-fibrotic efficacy of nintedanib in pulmonary fibrosis via the inhibition of fibrocyte activity

Background: Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear. Methods: Human monocytes were isolated from the peripheral blood of healthy volunteers. The expression of growth factors and their receptors in fibrocytes was analyzed using ELISA and Western blotting. The effects of nintedanib on the ability of fibrocytes to stimulate lung fibroblasts were examined in terms of their proliferation. The direct effects of nintedanib on the differentiation and migration of fibrocytes were also assessed. We investigated whether nintedanib affected the accumulation of fibrocytes in mouse lungs treated with bleomycin. Results: Human fibrocytes produced PDGF, FGF2, and VEGF-A. Nintedanib and specific inhibitors for each growth factor receptor significantly inhibited the proliferation of lung fibroblasts stimulated by the supernatant of fibrocytes. Nintedanib inhibited the migration and differentiation of fibrocytes induced by growth factors in vitro. The number of fibrocytes in the bleomycin-induced lung fibrosis model was reduced by the administration of nintedanib, and this was associated with anti-fibrotic effects. Conclusions: These results support the role of fibrocytes as producers of and responders to growth factors, and suggest that the anti-fibrotic effects of nintedanib are at least partly mediated by suppression of fibrocyte function

Is there a common latent cognitive construct for dementia estimation across two Chinese cohorts?

INTRODUCTION: It is valuable to identify common latent cognitive constructs for dementia prevalence estimation across Chinese aging cohorts. METHODS: Based on cognitive measures of 12015 Chinese Longitudinal Healthy Longevity Survey (CLHLS; 13 items) and 6623 China Health and Retirement Longitudinal Study (CHARLS; 9 items) participants aged 65 to 99 in 2018, confirmatory factor analysis was applied to identify latent cognitive constructs, and to estimate dementia prevalence compared to Mini-Mental State Examination (MMSE) and nationwide estimates of the literature. RESULTS: A common three-factor cognitive construct of orientation, memory, and executive function and language was found for both cohorts with adequate model fits. Crude dementia prevalence estimated by factor scores was similar to MMSE in CLHLS, and was more reliable in CHARLS. Age-standardized dementia estimates of CLHLS were lower than CHARLS among those aged 70+, which were close to the nationwide prevalence reported by the COAST study and Global Burden of Disease. DISCUSSION: We verified common three-factor cognitive constructs for both cohorts, providing an approach to estimate dementia prevalence at the national level. HIGHLIGHTS: Common three-factor cognitive constructs were identified in Chinese Longitudinal Healthy Longevity Survey (CLHLS) and China Health and Retirement Longitudinal Study (CHARLS). Crude dementia estimates using factor scores were reliable in both cohorts. Estimates of CHARLS were close to current evidence, but higher than that of CLHLS

FANCI serve as a prognostic biomarker correlated with immune infiltrates in skin cutaneous melanoma

BackgroundAs a member of tumor, Skin cutaneous melanoma (SKCM) poses a serious threat to people’s health because of its strong malignancy. Unfortunately, effective treatment methods for SKCM remain lacking. FANCI plays a vital role in the occurrence and metastasis of various tumor types. However, its regulatory role in SKCM is unclear. The purpose of this study was to explore the association of FANCI with SKCM.MethodsThis study investigated the expression of FANCI in GSE46517, GSE15605, and GSE114445 from the Gene Expression Omnibus database and The Cancer Genome Atlas (TCGA)-SKCM datasets using the package “limma” or “DESeq2” in R environment and also investigated the prognostic significance of FANCI by utilizing the GEPIA database. Additionally, our research made use of real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining to verify FANCI expression between SKCM and normal tissues and developed the knockdown of FANCI in A375 and A875 cells to further analyze the function of FANCI. Finally, this study analyzed the correlation of FANCI and tumor-infiltrating immune cells by CIBERSORT, ESTIMATE, and ssGSEA algorithms.ResultsThe FANCI level was increasing in SKCM tissues from GSE46517, GSE15605, GSE114445, and TCGA-SKCM. However, high FANCI expression correlated with poor overall survival. The RT-qPCR and IHC confirmed the accuracy of bioinformatics. Knocking down FANCI suppresses A375 and A875 cell proliferation, migration, and invasion. FANCI could be involved in the immunological milieu of SKCM by regulating immune responses and infiltrating numerous immune cells, particularly neutrophils, CD8+ T cells, and B cells. Furthermore, patients with SKCM who have a high FANCI expression level are reported to exhibit immunosuppression, whereas those with a low FANCI expression level are more likely to experience positive outcomes from immunotherapy.ConclusionsThe increased FANCI expression in SKCM can be a prognostic biomarker. Knockdown FANCI can reduce the occurrence and progression of SKCM. The FANCI expression provides a foundation for predicting the immune status and treatment of SKCM

Correlation between Insulin Resistance and Thyroid Nodule in Type 2 Diabetes Mellitus

Objective. The present study explored the association between insulin resistance (IR) and the clinical characteristics of thyroid nodules in patients with type 2 diabetes mellitus (T2DM). Methods. All the patients were newly diagnosed with T2DM. 201 patients with thyroid nodule disease and 308 patients without the nodular thyroid disease. The participants were evaluated by relevant examination. Correlation analyses and regression analyses were performed to examine the relationships between the two groups. Results. HOMA-IR values, serum FT4 (free thyroxine) levels, and age were higher in the thyroid nodule group than in the control group. The proportion of women in the thyroid nodule group is greater than the proportion of women in the control group. Logistic regression analysis showed that age, sex, FT4, and HOMA-IR were positive factors for thyroid nodule. The volume and size of the thyroid nodule were positively correlated with HOMA-IR, irrespective of gender. The thyroid nodule volume and size and the TSH (thyroid stimulating hormone) were greater in females than in males, whereas FT3 (free triiodothyronine) was lower in females. Conclusion. IR might be a risk factor for thyroid nodule. Whether alleviating the IR might slow the growth, or diminish the volume and size of the thyroid nodules, is yet to be elucidated

The Core/E1 domain of Hepatitis C virus genotype 4a in Egypt does not contain viral mutations or strains specific for hepatocellular carcinoma

[EN] Background: Hepatitis C virus (HCV) infection is a well-documented etiological factor for hepatocellular carcinoma (HCC). As HCV shows remarkable genetic diversity, an interesting and important issue is whether such a high viral genetic diversity plays a role in the incidence of HCC. Prior data on this subject are conflicting. Objectives: Potential association between HCV genetic mutations or strain variability and HCC incidence has been examined through a comparative genetic analysis merely focused on a single HCV subtype (genotype 4a) in a single country (Egypt). Study design: The study focused on three HCV sequence datasets with explicit sampling dates and disease patterns. An overlapping HCV Core/E1 domain from three datasets was used as the target for comparative analysis through genetic and phylogenetic approaches. Results: Based on partial Core/E1 domain (387 bp), genetic and phylogenetic analysis did not identify any HCC-specific viral mutations and strains, respectively. Conclusions: The Core/E1 domain of HCV genotype 4a in Egypt does not contain HCC-specific mutations or strains. Additionally, sequence errors resulting from the polymerase chain reaction, together with a strong evolutionary pressure on HCV in patients with end-stage liver disease, have significant potential to bias data generation and interpretation. (C) 2011 Elsevier B.V. All rights reserved.This work was supported by NIH grants R01 DK80711 (Dr. Xiaofeng Fan), R21 AI076834 (Dr. Adrian M. Di Bisceglie) and USA and Egypt Science and Technology Joint Fund BIO6-002-004 (Dr. Adrian M. Di Bisceglie).Zhang, X.; Ryu, SH.; Xu, Y.; Elbaz, T.; Zekri, AN.; Abdelaziz, AO.; Abdel-Hamid, M.... (2011). The Core/E1 domain of Hepatitis C virus genotype 4a in Egypt does not contain viral mutations or strains specific for hepatocellular carcinoma. Journal of Clinical Virology. 52(4):333-338. https://doi.org/10.1016/j.jcv.2011.08.022S33333852