Association of muscle mass, grip strength and fat-to-muscle ratio and metabolic dysfunction-associated steatotic liver disease in a middle-to-elderly aged population.

OBJECTIVE: The association of appendicular skeletal muscle mass (ASM), grip strength and fat-to-muscle ratio (FMR) and the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) are not well known. MATERIALS AND METHODS: This study included participants older than 40 years who underwent bioelectrical impedance assessment in Prevalence of Metabolic Diseases and Risk Factors in Shunde (SPEED-Shunde). We measured grip strength with an electronic grip strength metre. ASM and grip strength were adjusted by dividing body mass index (BMI). FMR was calculated as total fat mass to total muscle mass. Liver steatosis and liver fibrosis were evaluated by vibration-controlled transient elastography. Multifactorial logistic regression was used to analyse the relationship between ASM, grip strength, FMR, and MASLD or MASLD-associated liver fibrosis. We performed subgroup analyses according to sex, age and BMI. Interaction tests and linear trend tests were also conducted. RESULTS: This study included a total of 3277 participants. FMR was positively associated with MASLD (OR: 1.89, 95% CI: 1.66-2.15) and MASLD-associated liver fibrosis (OR: 1.70, 95% CI: 1.22-2.37). While ASM/BMI (OR: 0.59, 95% CI: 0.52-0.67) or grip strength/BMI (OR: 0.72, 95% CI: 0.66-0.78) were negatively associated with MASLD. Interactions were observed between ASM/BMI and age, grip strength and sex in MASLD, as well as FMR and MASLD-associated liver fibrosis. CONCLUSION: In a middle-to-elderly aged population, FMR was positively associated with the risk of MASLD and MASLD-associated liver fibrosis, and muscle mass and grip strength were negatively associated with MASLD, rather than MASLD-associated liver fibrosis.

Sex- and age-specific associations of serum essential elements with diabetes among the Chinese adults: a community-based cross-sectional study.

BACKGROUND: Although several studies have found the relationship between essential elements and diabetes, the studies about the association of essential elements with diabetes diagnosed according to an oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) in a sex- and age-specific manner were limited. To investigate the linear and nonlinear relationship of five essential elements including iron (Fe), copper (Cu), Zinc (Zn), magnesium (Mg), and calcium (Ca) with diabetes, fasting plasma glucose (FPG), 2-h postprandial plasma glucose (PPG), and HbA1c and to evaluate the sex- and age-specific heterogeneities in these relationships. METHODS: A total of 8392 community-dwelling adults were recruited to complete a questionnaire and undergo checkups of anthropometric parameters and serum levels of five metals (Fe, Cu, Zn, Mg, and Ca). The multivariable logistic and linear regression, the restricted cubic spline (RCS) analysis, and subgroup analysis were applied to find the associations between the essential elements and the prevalence of diabetes as well as FPG, PPG, and HbA1c. RESULTS: In the multivariable logistic regression and multivariable linear regression, serum Cu was positively associated with FPG, PPG, and HbA1c while serum Mg was significantly inversely correlated with FPG, PPG, HbA1c, and diabetes (all P < 0.001). In the RCS analysis, the non-linear relationship of Cu and diabetes (P < 0.001) was found. In the subgroup analysis, stronger positive associations of Cu with diabetes (P for interaction = 0.027) and PPG (P for interaction = 0.002) were found in younger women. CONCLUSIONS: These findings may lead to more appropriate approaches to essential elements supplementation in people with diabetes of different ages and sexes. However, more prospective cohort and experimental studies are needed to probe the possible mechanism of sex- and age-specific associations between serum essential elements and diabetes.

Sex-specific associations between the developmental alterations in the pituitary-thyroid hormone axis and thyroid nodules in Chinese euthyroid adults: a community-based cross-sectional study.

Background: Previous studies have revealed the sex-specific features of pituitary-thyroid hormone (TH) actions and the prevalence of thyroid nodules (TNs) in children and adolescents. However, it was unclear in adults. We aimed to investigate the features of pituitary-TH actions in women and men at different ages, and the associations of thyrotropin (TSH), THs, and central sensitivity to THs indices including the thyroid feedback quantile-based index by FT4 (TFQIFT4) and the thyroid feedback quantile-based index by FT3(TFQIFT3) with of TNs in Chinese euthyroid adults. Methods: 8771 euthyroid adults from the communities in China were involved. Demographic, behavioral, and anthropometric data were gathered through the questionnaires. Ultrasound was performed to evaluate the TNs. TSH and THs levels were measured. The multivariable logistic regression and multivariable ordinal logistic regression were conducted. Results: TFQIFT3 among both genders, except women aged 43 to 59 years, where it increased slightly. Additionally, there was an age-related decline in TFQIFT4 levels in both women and men at ages < 50 and < 53, respectively, but a marked increase after that. Lower TSH levels were significantly associated with a higher prevalence and lower odds of having fewer TNs using multiple nodules as the base category in both men and women (both P for trend < 0.05). Additionally, lower TFQIFT3 and TFQIFT4 levels were significantly associated with a higher prevalence of TNs in women (both P for trend < 0.05), and lower TFQIFT3 levels were significantly associated with a higher prevalence of TNs in men. Both higher TFQIFT3 and TFQIFT4 levels were significantly associated with higher odds of having fewer TNs using multiple nodules as the base category in women. However, the relationships between TFQIFT4 and the prevalence or number of TNs in men were not found. Conclusions: The trends of THs, TSH, TFQIFT4, and TFQIFT3 at different ages were sex-dependent. Both TFQIFT4 and TFQIFT3 levels were negatively associated with the prevalence and number of TNs in women. The present results may lead to a better understanding of the sex-specific relationships between the development of the pituitary-TH axis and the formation of TNs.

[Comparative analysis of plastomes of Rubus chingii and R. chingii var. suavissimus].

Rubus chingii and R. chingii var. suavissimus are unique dual-purpose plant resources, with significant nutraceutical, pharmaceutical, and economic value, as well as promising prospects for further development. To investigate the genetic structure and evolutionary characteristics of these two varieties, this study conducted plastome sequencing using the Illumina HiSeq XTen sequencing platform. Subsequently, the study performed assembly, annotation, and characterization of the genomes, followed by a comparative plastome and phylogenetic analysis using bioinformatics techniques. The results revealed that the plastomes of R. chingii and R. chingii var. suavissimus exhibited a tetrad structure, comprising a large single-copy region(LSC), a small single-copy region(SSC), and two inverted repeat regions(IRs). The study identified a total of 56 simple sequence repeats(SSRs) after comparative analysis, predominantly consisting of A and T. Furthermore, the structure of the IR boundary genes in both varieties was found to be highly conserved, with only minor nucleotide variations. Additionally, the study identified three highly variable regions: rps16-trnQ-psbK, trnR-atpA, and trnT-trnL, which held promise as potential identification marks for further development and utilization. Phylogenetic analysis results obtained by the maximum likelihood and Bayesian inference methods demonstrated a close clustering of R. chingii and R. chingii var. suavissimus(100% support), with their closest relatives being R. trianthus. This study, focusing on plastome-level genetic distinctions between these two varieties, lays a foundation for future species protection, development, and utilization.

Dipeptidyl peptidase 4 inhibitors vs. metformin for new-onset dementia: a propensity score-matched cohort study.

BACKGROUND: Hypoglycemic pharmacotherapy interventions for alleviating the risk of dementia remains controversial, particularly about dipeptidyl peptidase 4 (DPP4) inhibitors versus metformin. Our objective was to investigate whether the initiation of DPP4 inhibitors, as opposed to metformin, was linked to a reduced risk of dementia. METHODS: We included individuals with type 2 diabetes over 40 years old who were new users of DPP4 inhibitors or metformin in the Chinese Renal Disease Data System (CRDS) database between 2009 and 2020. The study employed Kaplan-Meier and Cox regression for survival analysis and the Fine and Gray model for the competing risk of death. RESULTS: Following a 1:1 propensity score matching, the analysis included 3626 DPP4 inhibitor new users and an equal number of metformin new users. After adjusting for potential confounders, the utilization of DPP4 inhibitors was associated with a decreased risk of all-cause dementia compared to metformin (hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.45-0.89). Subgroup analysis revealed that the utilization of DPP4 inhibitors was associated with a reduced incidence of dementia in individuals who initiated drug therapy at the age of 60 years or older (HR 0.69, 95% CI 0.48-0.98), those without baseline macrovascular complications (HR 0.62, 95% CI 0.41-0.96), and those without baseline microvascular complications (HR 0.67, 95% CI 0.47-0.98). CONCLUSION: In this real-world study, we found that DPP4 inhibitors presented an association with a lower risk of dementia in individuals with type 2 diabetes than metformin, particularly in older people and those without diabetes-related comorbidities.

Association of metabolic syndrome and sarcopenia with all-cause and cardiovascular mortality: a prospective cohort study based on the NHANES.

Background: Metabolic syndrome (MetS) and sarcopenia (SP) have emerged as significant public health concerns in contemporary societies, characterized by shared pathophysiological mechanisms and interrelatedness, leading to profound health implications. In this prospective cohort study conducted within a US population, we aimed to examine the influence of MetS and SP on all-cause and cardiovascular mortality. Methods: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) III for the years 1999-2006 and 2011-2018, and death outcomes were ascertained by linkage to National Death Index (NDI) records through December 31, 2019. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cardiovascular mortality. In addition, subgroup and sensitivity analyses were conducted to test the robustness of the results. Results: Over a median follow-up period of 13.3 years (95% CI: 12.8-13.8), 1714 deaths were observed. The groups characterized by MetS-/SP+, MetS+/SP-, and MetS+/SP+ exhibited higher all-cause mortality rates in comparison to the MetS-/SP- group, with the MetS+/SP+ group (HR 1.76, 95% CI: 1.37-2.25) displaying the highest all-cause mortality. Increased cardiovascular mortality was observed in the MetS+/SP- (HR 1.84, 95% CI: 1.24-2.72), and MetS+/SP+ groups (HR 2.39, 95% CI: 1.32-4.35) compared to the MetS-/SP- group, whereas it was not statistically significant in the MetS-/SP+ group. However, among males and individuals aged < 60, the presence of both MetS and SP (MetS+/SP+ group) was found to be significantly associated with a higher risk of all-cause and cardiovascular mortality. Conclusion: The coexistence of MetS and SP increased the risk of all-cause and cardiovascular mortality, particularly in males and in nonelderly populations. Individuals with either MetS or SP may require more careful management to prevent the development of other diseases and thereby reduce mortality.

Prevalence and risk factors of MAFLD and its metabolic comorbidities in community-based adults in China: A cross-sectional study.

AIMS: There is a growing interest in the co-management of metabolic dysfunction-associated fatty liver disease (MAFLD) and its metabolic comorbidities. However, there is insufficient epidemiological data regarding MAFLD and its metabolic comorbidities in China. This study aims to investigate the prevalence and risk factors of MAFLD and its metabolic comorbidities. METHODS: 9171 participants were recruited in this cross-sectional study, utilizing a multistage, stratified sampling method. All participants underwent a comprehensive assessment. The diagnosis of MAFLD was based on vibration-controlled transient elastography (VCTE). The prevalence of MAFLD and its metabolic comorbidities was calculated. Binary and ordinary logistic regressions were conducted. RESULTS: The overall weighted prevalence of MAFLD was 21.18%. Of the 2081 adults with MAFLD, 1866 (89.67%) had more than one metabolic comorbidity, and only 215 (10.33%) did not have comorbidity. Among the population with MAFLD, the prevalence of dyslipidemia, hypertension, hyperuricemia, and diabetes was 67.47%, 43.73%, 39.10%, and 33.88%, respectively. Advanced age, male gender, overweight/obesity, excessive alcohol consumption, and elevated HOMA-IR levels were positively correlated with the number of MAFLD-related metabolic comorbidities. CONCLUSIONS: A significant proportion of individuals diagnosed with MAFLD presented with metabolic comorbidities. Therefore, engaging in the co-management of MAFLD and its metabolic comorbidities is imperative.

Associations of thyroid feedback quantile-based index with diabetes in euthyroid adults in the United States and China.

BACKGROUND: We aimed to investigate the associations between thyroid hormone sensitivity indices and diabetes in euthyroid adults in the United States and China. METHODS: 2296 euthyroid adults from the NHANES in the United States and 8319 euthyroid adults from the SPEED-Shunde in China were involved. The thyroid sensitivity indices, namely TFQIFT4 and TFQIFT3, were calculated. Multivariable logistic regression, restricted cubic spline analysis, and general ordinal logit regression were utilized. RESULTS: In the NHANES, compared with participants in quartile 1st (Q1), those in Q4 of TFQIFT3 (OR 2.12, 95% CI (1.18, 3.81)) and those in Q3 of TFQIFT4 (OR 2.31, 95% CI (1.18, 4.53)) (both P for trend < 0.05) were associated with a greater prevalence of diabetes. In the SPEED-Shunde, compared with participants in Q1, those in Q4 of TFQIFT3 had a greater prevalence of diabetes (OR 1.36, 95% CI (1.11, 1.66) (P for trend < 0.05), while no significant associations between TFQIFT4 and diabetes were found. CONCLUSIONS: TFQIFT3 was associated with a higher prevalence of diabetes both in the United States and China. However, TFQIFT4 was only associated with a higher prevalence of diabetes in the United States, not in China. Further prospective cohort studies are necessary to validate these findings.

Association of sensitivity to thyroid hormones with all-cause mortality in euthyroid US adults: A nationwide cohort study.

Background This study aimed to examine the associations of thyroid hormone sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, thyroid feedback quantile-based index by FT4 (TFQIFT4), thyroid-stimulating hormone index (TSHI), and thyrotrophic thyroxine resistance index (TT4RI) with all-cause mortality in euthyroid adults. Methods The study included 6243 euthyroid adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. FT3/FT4 ratio, TFQIFT4, TSHI, and TT4RI were calculated. The multivariable Cox proportional hazard regression, restricted cubic spline (RCS), and subgroup analysis were conducted. Results Individuals in quartile 4th (Q4) had lower all-cause mortality than those in quartile 1st (Q1) of FT3/FT4 ratio (OR 0.70, 95% CI (0.51, 0.94)). Regarding TFQIFT4, individuals in Q4 of TFQIFT4 had a 43% higher all-cause mortality than those in Q1 (OR 1.43, 95% CI (1.05, 1.96)) (P <0.05, all). Compared with participants in Q1, no associations of TSHI and TT4RI with mortality were found. TFQIFT4 was linearly and positively associated with mortality. However, the FT3/FT4 ratio showed a U-shaped association with mortality. Conclusions Increased risk for all-cause mortality was positively associated with TFQIFT4, suggesting that increased risk for all-cause mortality was associated with decreased central sensitivity to thyroid hormones. Furthermore, the FT3/FT4 ratio showed a U-shaped association with mortality, with an inflection point at 0.5. However, more cohort studies are needed to validate the conclusions.

Projected income data under different shared socioeconomic pathways for Washington state.

High-resolution income projections under different Shared Socioeconomic Pathways (SSPs) are essential for the climate change research communities to devise climate change adaptation and mitigation strategies. To generate income projections for Washington state, we obtain state-level GDP per capita projections and convert them into projected annual household income. The resulting state-level income projections are subsequently downscaled to the census block-level based on the Longitudinal Origin-Destination Employment Statistics (LODES) dataset. For accuracy assessment, we downscale historical income data from state- level to block- and block group-level and compare the downscaled results against the actual income data from LODES. County-level accuracy assessment is also conducted based on American Community Survey. The results demonstrate a good agreement (Average R2 of 0.67, 0.8, and 0.99 for block-, block group-, and county-level, respectively) between the downscaled income data and the reference data, thereby validating the methodology employed. Our approach is applicable to other states for income projections, which can be utilized by a broader audience, including those involved in demographic analysis, economic research, and urban planning.

Associations of Serum Iron Status with MAFLD and Liver Fibrosis in the USA: a Nationwide Cross-Section Study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology characterized by liver steatosis. Iron status is related to many metabolic diseases. However, the researches on the associations of serum iron status with MAFLD are limited. The objective of this study was to investigate the associations of serum iron status biomarkers with MAFLD and liver fibrosis. A total of 5892 adults were enrolled in the current cross-sectional study using the 2017-March 2020 National Health and Nutrition Examination Survey. Liver steatosis and liver fibrosis were defined by the median values of controlled attenuation parameter ≥ 274 dB/m and liver stiffness measurement ≥ 8 kPa, respectively. The multivariable logistic/linear regression and restricted cubic spline analysis were conducted. After adjusting for potential confounders, higher ferritin levels were associated with higher odds of MAFLD (OR 4.655; 95% CI 2.301, 9.418) and liver fibrosis (OR 7.013; 95% CI 3.910, 12.577). Lower iron levels were associated with a higher prevalence of MAFLD (OR 0.622; 95% CI 0.458, 0.844) and liver fibrosis (OR 0.722; 95% CI 0.536, 0.974). Lower transferrin saturation (TSAT) was associated with a higher prevalence of MAFLD (OR 0.981; 95% CI 0.970, 0.991) and liver fibrosis (OR 0.988; 95% CI 0.979, 0.998). Higher ferritin levels, lower iron levels, and TSAT were associated with a higher prevalence of MAFLD and liver fibrosis. This study extended the knowledge of modifying iron status to prevent MAFLD and liver fibrosis. More prospective and mechanism studies were warranted to confirm the conclusions.

Sex-Specific Associations of Five Serum Essential Metal Elements with Thyroid Nodules in Euthyroid Adults: a Cross­sectional Study.

The association between the serum essential metal elements (magnesium, iron, copper, zinc, and calcium) and thyroid nodules is still inconsistent. The current study aims to investigate the relationship of metal elements with thyroid nodules and their malignant tendency. A total of 6480 Chinese euthyroid adults were included in our study. We collect basic information through questionnaires and medical checkups. We diagnose thyroid nodules by ultrasound and detect serum trace metal concentrations by using an automatic biochemical analyzer. Binary and multinomial logistic regressions were used to investigate the associations. As a result, we found that serum copper concentrations were positively associated with thyroid nodules in the second, third, and fourth quartiles, compared to the first quartile (P = 0.024, P = 0.016, P = 0.032) in women and P for trend is 0.038. There is a significant sex-specific association between copper concentrations and thyroid nodules (P for interaction = 0.009). The results of the multinomial logistic regression analyses indicate high serum calcium and magnesium concentrations emerged as consistent risk factors for thyroid nodules in both genders, whereas low zinc was a sex-specific factor. We also observed significant sex interactions in the relationships of magnesium (P for interaction = 0.043) with thyroid nodules with malignant tendency among participants with thyroid nodules. In conclusion, our study suggests that gender is an important factor when studying the association between serum metals and thyroid nodules. The imbalance of selected metal elements (calcium, copper, zinc, and magnesium) may relate to thyroid nodules and their malignant tendency, and future prospective studies are needed to further confirm the associations.

Biochar amendment combined with partial root-zone drying irrigation alleviates salinity stress and improves root morphology and water use efficiency in cotton plant.

An adsorption experiment and a pot experiment were executed in order to explore the mechanisms by which biochar amendment in combination with reduced irrigation affects sodium and potassium uptake, root morphology, water use efficiency, and salinity tolerance of cotton plants. In the adsorption experiment, ten NaCl concentration gradients (0, 50, 100, 150, 200, 250, 300, 350, 400, and 500 mM) were set for testing isotherm adsorption of Na+ by biochar. It was found that the isotherms of Na+ adsorption by wheat straw biochar (WSP) and softwood biochar (SWP) were in accordance with the Langmuir isotherm model, and the Na+ adsorption ability of WSP (55.20 mg g-1) was superior to that of SWP (47.38 mg g-1). The pot experiment consisted three factors, viz., three biochar amendments (no biochar, WSP, and SWP), three irrigation strategies (deficit irrigation, partial root-zone drying irrigation - PRD, full irrigation), and two NaCl concentrations gradients (0 mM and 200 mM). The findings indicated that salinity stress lowered K+ concentration, root length, root surface area, and root volume (RV), but increased Na+ concentration, root average diameter, and root tissue density. However, biochar amendment decreased Na+ concentration, increased K+ concentration, and improved root morphology. In particular, the combination of WSP and PRD increased K+/Na+ ratio, RV, root weight density, root surface area density, water use efficiency, and partial factor productivity under salt stress, which can be a promising strategy to cope with drought and salinity stress in cotton production.

Targeting autophagy with SAR405 alleviates doxorubicin-induced cardiotoxicity.

Anthracycline antitumor agents, such as doxorubicin (DOX), are effective in the treatment of solid tumors and hematological malignancies, but anthracycline-induced cardiotoxicity (AIC) limits their application as chemotherapeutics. Dexrazoxane (DEX) has been adopted to prevent AIC. Using a chronic AIC mouse model, we demonstrated that DEX is insufficient to reverse DOX-induced cardiotoxicity. Although therapies targeting autophagy have been explored to prevent AIC, but whether novel autophagy inhibitors could alleviate or prevent AIC in clinically relevant models needs further investigation. Here, we show that genetic ablation of Atg7, a key regulator in the early phase of autophagy, protected mice against AIC. We further demonstrated that SAR405, a novel autophagy inhibitor, attenuated DOX-induced cytotoxicity. Intriguingly, the combination of DEX and SAR405 protected cells against DOX-induced cardiotoxicity in vivo. Using the cardiomyocyte cell lines AC16 and H9c2, we determined that autophagy was initiated during AIC. Our results suggest that inhibition of autophagy at its early phase with SAR405 combined with DEX represents an effective therapeutic strategy to prevent AIC.

Associations between blood essential metal mixture and serum uric acid: a cross-sectional study.

Introduction: Although several studies have explored the associations between single essential metals and serum uric acid (SUA), the study about the essential metal mixture and the interactions of metals for hyperuricemia remains unclear. Methods: We performed a cross-sectional study to explore the association of the SUA levels with the blood essential metal mixture, including magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), zinc (Zn), manganese (Mn) in Chinese community-dwelling adults (n=1039). The multivariable linear regression, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were conducted to estimate the associations of blood essential metals with SUA levels and the BKMR model was also conducted to estimate the interactions of the essential metals on SUA. Results: In the multivariable linear regression, the association of blood Mg, Mn, and Cu with SUA was statistically significant, both in considering multiple metals and a single metal. In WQS regression [ß=13.59 (95%CI: 5.57, 21.60)] and BKMR models, a positive association was found between the mixture of essential metals in blood and SUA. Specifically, blood Mg and Cu showed a positive association with SUA, while blood Mn showed a negative association. Additionally, no interactions between individual metals on SUA were observed. Discussion: In conclusion, further attention should be paid to the relationship between the mixture of essential metals in blood and SUA. However, more studies are needed to confirm these findings.

25-Hydroxyvitamin D Is Associated with Islet Homeostasis in Type-2 Diabetic Patients with Abdominal Obesity.

OBJECTIVE: Islet α cells input is essential for insulin secretion from ß cells. The present study aims to investigate the association between 25-hydroxyvitamin D [25(OH)D] and islet function homeostasis in type-2 diabetes (T2D) patients. METHODS: A total of 4670 T2D patients from seven communities in Shanghai, China were enrolled. The anthropometric indices, biochemical parameters, serum 25(OH)D, and islet function [including C-peptide (C-p) and glucagon] were measured. RESULTS: The fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), glucagon, and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased. Next, the population was divided into two groups: abdominal obesity and non-abdominal obesity groups. After adjustment, the 25(OH)D level was found to be associated with HbA1c, glucagon, and homeostasis model assessment of ß (HOMA-ß) in the non-abdominal obesity group. There was a significant relationship between 25(OH)D and HbA1c, glucagon, HOMA-IR, baseline insulin or C-p in the abdominal obesity group. In the abdominal obesity group, the ordinary least squares (OLS) regression and quantile regression revealed that 25(OH) D was obviously associated with glucagon and fasting C-p levels. In the abdominal obesity group, the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p (P=0.0124). Furthermore, the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation (SD) below the mean (P=0.0002), and lower at the mean of the course of diabetes (P=0.0007). CONCLUSION: 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity. The 25(OH)D influenced C-p in part by influencing glucagon. The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity, in terms of islet homeostasis, is influenced by the course of diabetes.

Optimized risk stratification strategy for glioma patients based on the feature genes of poor immune cell infiltration patterns.

BACKGROUND: Gliomas, originating from glial cells within the brain or spinal cord, are common central nervous system tumors with varying degrees of malignancy that influence the complexity and difficulty of treatment. The current strategies, including traditional surgery, radiotherapy, chemotherapy, and emerging immunotherapies, have yielded limited results. As such, our study aims to optimize risk stratification for a more precise treatment approach. We primarily identify feature genes associated with poor immune cell infiltration patterns through various omics algorithms and categorize glioma patients based on these genes to enhance the accuracy of patient prognosis assessment. This approach can underpin individualized treatment strategies and facilitate the discovery of new therapeutic targets. METHODS: We procured datasets of gliomas and normal brain tissues from TCGA, CGGA, and GTEx databases. Clustering was conducted using the input of 287 immune cell feature genes. Hub genes linked with the poor prognosis subtype (C1) were filtered through WGCNA. The TCGA dataset served as the discovery cohort and the CGGA dataset as the external validation cohort. We constructed a prognostic model related to feature genes from poor immune cell infiltration patterns utilizing LASSO-Cox regression. Comprehensive analyses of genomic heterogeneity, tumor stemness, pathway relevance, immune infiltration patterns, treatment response, and potential drugs were conducted for different risk groups. Gene expression validation was performed using immunohistochemistry (IHC) on 98 glioma samples and 11 normal brain tissue samples. RESULTS: Using the filtered immune cell-related genes, glioma patients were stratified into C1 and C2 subtypes through clustering. The C1 subtype exhibited a worse prognosis, with upregulated genes primarily enriched in immune response, extracellular matrix, etc., and downregulated genes predominantly enriched in neural signal transduction and neural pathway-related aspects. Seven advanced algorithms were used to elucidate immune cell infiltration patterns of different subtypes. In addition, WGCNA identified hub genes from poor immune infiltration patterns, and a prognostic model was constructed accordingly. High-risk patients demonstrated shorter survival times and higher risk scores as compared to low-risk patients. Multivariate Cox regression analysis revealed that, after adjusting for confounding clinical factors, risk score was a vital independent predictor of overall survival (OS) (P < 0.001). The established nomogram, which combined risk scores with WHO grade and age, accurately predicted glioma patient survival rates at 1, 3, and 5 years, with AUCs of 0.908, 0.890, and 0.812, respectively. This risk score enhanced the nomogram's reliability and informed clinical decision-making. We also comprehensively analyzed genomic heterogeneity, tumor stemness, pathway relevance, immune infiltration patterns, treatment response, and potential drugs for different risk groups. In addition, we conducted preliminary validation of the potential PLSCR1 gene using IHC with a large sample of gliomas and normal brain tissues. CONCLUSION: Our optimized risk stratification strategy for glioma patients has the potential to improve the accuracy of prognosis assessment. The findings from our omics research not only enhance the understanding of the functions of feature genes related to poor immune cell infiltration patterns but also offer valuable insights for the study of glioma prognostic biomarkers and the development of individualized treatment strategies.