Nonalcoholic steatohepatitis (NASH) is a metabolic disorder, and immune-mediated inflammation plays an important role in the progression of the disease. AdipoR2, encoded by ADIPOR2, is closely involved in the pathogenesis of NASH through adiponectin signaling. However, the relationship between ADIPOR2 and the immune microenvironment and metabolic dysfunction in NASH patients remains unexplored. NASH datasets were collected from the public database. ADIPOR2 expression level and its diagnostic value were explored. Then, the relationships among ADIPOR2, the immune microenvironment, and metabolic dysfunction were investigated. ADIPOR2-related genes were identified, a regulatory network was established, and drug sensitivity analysis was conducted. In addition, ADIPOR2 was also verified in clinical samples. ADIPOR2 expression was significantly increased in NASH patients compared to healthy controls and shows better diagnostic value. Immune infiltration analysis found that T cells CD4 memory resting and dendritic cells resting were significantly different in healthy controls versus NASH patients, and ADIPOR2-low versus ADIPOR2-high expression groups. Gene set enrichment analysis and gene set variation analysis showed that metabolism-related pathways (such as HALLMARK_CHOLESTEROL_HOMEOSTASIS, HALLMARK_FATTY_ACID_METABOLISM, and HALLMARK_PEROXISOME) were significantly upregulated in NASH and ADIPOR2-high expression groups. Correlation analysis revealed that ADIPOR2 expression was closely linked to these immune cells and metabolism-related pathways. Then, 16 ADIPOR2-related genes were identified, and the miRNAs-ADIPOR2-TFs regulatory network was constructed. In addition, patients in the ADIPOR2-low expression group showed higher sensitivity to drugs. ADIPOR2 may be a potential diagnostic target and could be related to immune cells and metabolic dysfunction in NASH.

Testosterone is also known as a metabolic hormone, playing a crucial regulatory role in the metabolism of carbohydrates, fats, and proteins. The testosterone levels of adult male patients with type 2 diabetes are significantly reduced, which affects blood glucose control and insulin resistance. At the same time, poor blood glucose control can exacerbate testosterone deficiency. Various diabetes treatment regimens may have different effects on testosterone. In recent years, numerous clinical studies have confirmed that testosterone replacement therapy can effectively prevent and even reverse early-stage type 2 diabetes. Therefore, in this chapter, we will describe the relevant clinical evidence and mechanisms of the interaction between testosterone levels and blood glucose control.

ObjectivesThe prevalence of type 2 diabetes mellitus has increased worldwide and is higher among older individuals. Exploring the mechanisms underlying pancreatic β-cell dysfunction may help elucidate the pathogenesis of age-related diabetes.MethodsIslet function-related parameters were measured in four young and four aged mice. Endogenous proteins and metabolites in the pancreas were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics and metabolomics, and integrated data analysis was performed.ResultsCompared with young mice, aged mice presented higher fasting blood glucose levels and insulin resistance index (according to the homeostatic model assessment for insulin resistance, HOMA-IR), whereas that from the homeostasis model assessment of β-cell function (HOMA-β) significantly decreased. A total of 3,795 proteins were quantified, 57 of which were upregulated and 50 were downregulated in aged mice. Moreover, 46 metabolites were significantly upregulated and 19 were downregulated in aged mice. Integrated proteomic and metabolomic analyses revealed six significant pathways implicated in these changes, including arginine biosynthesis and the pentose phosphate pathway. By integrating comprehensive multi-omics data, the arginine biosynthesis-related metabolites aspartate and glutamine were found to be associated with the aging phenotype and islet function.ConclusionThese findings suggest that concurrent endogenous protein and metabolite disturbances occur in the pancreas of aged mice, and metabolite aspartate and glutamine may serve as potential biomarkers and therapeutic targets for aging-related pancreatic dysfunction.

BACKGROUND:Polycystic ovary syndrome (PCOS) is a neuroendocrine-metabolic disorder with no approved drugs. Hypothalamic-pituitary-ovarian (HPO) axis dysfunction is core pathogenesis, and metabolic heterogeneity complicates treatment. Existing medications rarely ameliorate PCOS comprehensively. Sangzhi alkaloids (SZ-A), an extract from Morus alba L. twigs approved for type 2 diabetes in China, have not been systematically explored for PCOS. PURPOSE:To clarify the therapeutic effect and the mechanisms of SZ-A in PCOS. STUDY DESIGN:Animal studies, in vitro experiments and a placebo-controlled clinical trial. MATERIALS AND METHODS:In vivo: Obese/non-obese PCOS rats received oral SZ-A 67, 100, 150 mg/(kg·d) for 21 days (positive controls: Diane-35, metformin). In vitro: Granulosa cell apoptosis induced by dihydrotestosterone was treated with SZ-A 25, 50, 100, 200 μg/ml. CLINICAL:6-month placebo-controlled trial (128 PCOS patients; oral SZ-A 300 mg/d, n = 88; placebo, n = 40). Multi-omics/Western blotting explored HPO pathways. RESULTS AND DISCUSSION:In rats, SZ-A (67 to 150 mg/(kg·d), 21 days) dose-dependently reduced androgens, regularized estrous cycles, and improved ovarian morphology. In vitro, SZ-A (25 to 200 μg/ml) protected granulosa cells from apoptosis. In patients, 6-month SZ-A (300 mg/d) lowered free androgen index and improved menstrual regularity versus placebo. Mechanistically, SZ-A inhibited hyperandrogenism-induced granulosa cell apoptosis and regulated GnRH secretion and downstream signaling pathways. CONCLUSION:SZ-A exerts therapeutic effects on PCOS by modulating HPO axis function through multiple pathways. TRIAL REGISTRATION:ChiCTR2200065097.

In the era of precision medicine, the classification of diabetes mellitus has evolved beyond the traditional categories. Various classification methods now account for a multitude of factors, including variations in specific genes, type of β-cell impairment, degree of insulin resistance, and clinical characteristics of metabolic profiles. Improved classification methods enable healthcare providers to formulate blood glucose management strategies more precisely. Applying these updated classification systems, will assist clinicians in further optimising treatment plans, including targeted drug therapies, personalized dietary advice, and specific exercise plans. Ultimately, this will facilitate stricter blood glucose control, minimize the risks of hypoglycaemia and hyperglycaemia, and reduce long-term complications associated with diabetes.

Sensorineural hearing loss (SNHL)'s incidence is on the rise, severely affecting the quality of life of patients and even causing psychological and mental damage. It also poses a heavy burden on the global healthcare system. The auditory process involves the conversion of mechanical signals generated by the vibration of the basilar membrane into electrical signals by sensory hair cells. These signals are then transmitted to the spiral ganglion neurons, which receive input from inner hair cells and relay the information to the cochlear nucleus in the brainstem, and subsequently to the auditory cortex. Calcium plays a crucial role in this process, influencing homeostasis of the cochlear environment, the mechanoelectrical transduction channels and synaptic neurotransmitter release. Due to the increasing risks associated with aging, noise exposure, ototoxic drugs, and genetic mutations, the incidence of SNHL is continuously rising. Notably, SNHL often manifests as a disruption of calcium homeostasis. Therefore, it is essential to understand the potential mechanisms of calcium signaling in SNHL, providing new insights into the pathogenesis and treatment of SNHL. This review focuses on the mechanisms of calcium signaling in SNHL, including factors affecting calcium homeostasis and potential therapeutic approaches.

BackgroundBreast cancer (BC) is the leading malignant tumors among females worldwide, which serves as a common chronic disease with several acute postoperative complications, including upper limb edema, hemorrhage, flap necrosis, effusion and so on. A majority of BC patients have lymph node metastasis, suffering from a poor prognosis. The immune system has been reported to participate in regulating BC lymph node metastasis. This study aimed to search for immune-related biomarkers for predicting BC lymph node metastasis.Methods1057 BC patients were acquired from The Cancer Genome Atlas (TCGA) database as the training dataset while 327 BC patients were obtained from GSE20685 as the validation dataset. We get 2,175 immune genes from four immune-related gene sets. We divided BC patients into lymph node positive and negative groups to identify immune-related lymph node-associated differentially expressed genes (DEGs) for functional enrichment analysis and protein-protein interaction (PPI) network. In order to predict BC lymph node metastasis, we established an immune-related signature and assessed its predictive accuracy. In addition, we applied qRT-PCR to investigate signature gene expressions between normal breast epithelium cells and breast cancer cells.ResultsWe identified 336 immune-related lymph node-associated DEGs, which were enriched in leukocyte migration, immunoglobulin complex and receptor ligand activity among GO analysis and cytokine-cytokine receptor interaction among KEGG analysis. With the aim of predicting BC lymph node metastasis, we established a seven-gene immune-related signature, consisting of F2R, IKZF2, NAB1, RFX5, S100B, S1PR2 and VEGFA. The immune-related signature was proven to be an independent predictive factor for BC lymph node metastasis in both TCGA and GSE20685 databases. Compared with normal breast epithelium cells, RFX5, VEGFA were upregulated in breast cancer cells, IKZF2, NAB1, S100B were downregulated in breast cancer cells while F2R, S1PR2 showed no significance.ConclusionWe established a seven-gene immune-related signature for predicting lymph node metastasis in BC, which might provide a novel sight for BC diagnosis and treatment.

BACKGROUND:Polycystic ovary syndrome (PCOS) is a polygenic multifactorial systemic inflammatory autoimmune disease. Mulberry twig (MT) has pharmacological activities such as anti-inflammatory, hypoglycemic, anti-oxidant, and insulin resistance. Our study aimed to understand whether MT can affect PCOS and to assess its potential targets. METHODS:PCOS targets were searched using the OMIM, TTD, and GeneCards databases. The active components and corresponding protein targets of MT were searched in the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the compound-target network was constructed using Cytoscape 3.8.0. The intersection of the compound and disease targets was obtained, and the coincidence target was imported into the STRING database to construct a protein-protein interaction (PPI) network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on these targets. Finally, molecular docking methods were used to confirm the high affinity between the bioactive molecules of MT and their targets in PCOS. RESULTS:TCMSP database results showed that the 3 active components of MT acted against PCOS. The PPI network and core target analysis suggested that AKT1, TNF, and CASP3 are key targets of PCOS. KEGG analysis showed that MT treatment in PCOS mainly involved fluid shear stress and atherosclerosis. GO analysis showed that positive regulation of the apoptotic process, caveola, and enzyme binding play an important role in MT in PCOS. Molecular docking methods confirmed the high affinity between the bioactive molecules of MT and their targets in PCOS. CONCLUSION:MT may serve as a promising therapeutic candidate for PCOS, as verified by the network pharmacology approach based on data mining and molecular docking methods. However, further in vivo and in vitro experiments are needed.

Background Hypoglycemia remains a major barrier to optimal glycemic control in diabetes. Counter-regulatory hormonal responses, particularly those involving the pituitary and adrenal systems, play a central role in mitigating hypoglycemia, yet differences between diabetes subtypes are not well characterized. We aimed to investigate pituitary-target gland responses to hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM). Methods We enrolled drug-naive patients with newly diagnosed T2DM or T1DM, along with controls who did not have diabetes. Participants with diabetes received insulin pump therapy until normoglycemia was achieved. Hyperinsulinemic euglycemic-hypoglycemic clamps were then performed in all participants. Hormonal profiles of the pituitary-adrenal axis and C-peptide were serially measured during the clamps. Results During hypoglycemic clamps, C-peptide, thyroid-stimulating hormone, estradiol, and testosterone decreased, whereas prolactin, adrenocorticotropic hormone (ACTH), cortisol, and growth hormone (GH) increased significantly according to repeatedmeasures analysis of variance (ANOVA) (P<0.05 for all). Compared to controls and T2DM, patients with T1DM exhibited elevated basal GH (P=0.002) and an exaggerated GH response to hypoglycemia (P=0.002), with earlier onset and sustained elevation. In contrast, patients with T2DM showed higher ACTH (P=0.024) and cortisol (P=0.043) levels during hypoglycemia compared to controls and T1DM. Relative to the T1DM group, the T2DM group demonstrated lower testosterone and higher estradiol levels during hypoglycemia (P<0.001 for both). Conclusion Distinct diabetes subtypes demonstrate divergent pituitary-adrenal counter-regulatory responses to hypoglycemia, suggesting unique pathogenic mechanisms contributing to glycemic variability. The exaggerated GH response in T1DM may aggravate glucose fluctuations, whereas elevated ACTH and cortisol in T2DM could perpetuate insulin resistance.

Premixed insulin combines two types of insulin in a single injection. This combination streamlines dosing for patients with type 1 or type 2 diabetes, thereby enhancing convenience. However, patients receiving premixed insulin commonly have less satisfactory blood glucose control. The fixed ratio of insulin in these formulations frequently fails to account for the nuanced demands of individualized glucose-lowering therapy. Moreover, local absorption of mixed insulin and potential systemic autoimmune responses may further compromise glycaemic control. The co-formulation of insulin degludec and insulin aspart introduces a new combination of the two insulin types within a single injection, offering a promising solution for mitigating the limitations inherent in premixed insulin.

Background:The link between thyroid function and insulin resistance and metabolic dysfunction-associated fatty liver disease (MASLD) is becoming increasingly recognized. The primary goal of this study was to investigate the relationship between free triiodothyronine (FT3) levels, the triglyceride-glucose index (TyG) index, and the likelihood of MASLD in euthyroid individuals. Methods:A cross-sectional analysis of 18,298 euthyroid individuals was conducted, comparing 6,144 with MASLD to 12,154 controls. The study evaluated indicators related to clinical, metabolic, and thyroid function. The combined effect of the FT3 and TyG index on the likelihood of MASLD was assessed using logistic regression. Results:The MASLD group presented with higher male prevalence, older age, and increased rates of hypertension and diabetes. Significant correlations were observed between FT3, TyG, and metabolic parameters. After controlling for potential confounders, FT3 remained significantly associated with increased MASLD risk (adjusted OR = 1.35, 95% CI: 1.23-1.49; P < 0.001). Similarly, the TyG index was independently associated with higher MASLD risk (adjusted OR = 3.99, 95% CI: 3.40-4.68; P < 0.001). The high FT3 (≥ 4.98 pmol/L)/high TyG (≥ 8.55) group exhibited significantly elevated MASLD risk compared to the low FT3/low TyG group (OR = 5.38, 95% CI: 4.62-6.26; P < 0.001). Conclusion:Elevated FT3 and TyG index are independently associated with an increased risk of MASLD, and they exhibit a significant synergistic additive interaction.

Purpose:The mechanism of the dawn phenomenon remains poorly understood, and no targeted therapies are currently available. Emerging evidence suggests thyroid dysfunction may contribute to dawn phenomenon by modulating hepatic glucose output, insulin sensitivity, and β-cell function. This study utilized continuous glucose monitoring (CGM) to identify patients with type 2 diabetes exhibiting dawn phenomenon and to investigate its association with thyroid feedback efficiency. Patients and Methods:This study included patients with type 2 diabetes. All patients underwent CGM before any adjustments to their glucose-lowering therapy. The dawn phenomenon was determined if the elevation of blood glucose from 3 AM to 7 AM was more than 1.11 mmol/L. Clinical data, including medications, diabetic complications and comorbidities, biochemical markers, hemoglobin A1c (HbA1c), beta-cell function, and thyroid function, were recorded. Results:A total of 524 patients were included, of whom 265 (50.6%) exhibited the dawn phenomenon. A control group of 216 patients was matched based on HbA1c levels from those without dawn phenomenon using propensity score matching. The standard deviation of blood glucose (SDBG) (2.26 vs 1.78, P=0.001) and coefficient of variation (CV) (22.86 vs 16.97, P<0.001) were significantly higher in the dawn phenomenon group compared to the non-dawn phenomenon group. Thyroid feedback quantile-based index (TFQI) of free thyroxine (FT4) was negatively correlated with the elevation of blood glucose from 3 AM to 7 AM (BG 3-7) (r=-0.211, P=0.002). Low-density lipoprotein (LDL) showed a positive correlation with fasting blood glucose (r=0.242, P=0.001) and BG 3-7 (r=0.123, P=0.083). Regression analysis indicated that TFQI of free triiodothyronine (FT3) (β=-2.399, P<0.001) and LDL (β=0.550, P=0.004) were independent predictors of BG 3-7. Conclusion:The dawn phenomenon significantly correlates with glycemic fluctuation severity and TFQI. These findings indicate the relationship between thyroid hormones and glucose regulation, providing new insights into the mechanism of the dawn phenomenon.

Patients on premixed insulin therapy usually have poor glycemic control. This study aimed to investigate the effect of vildagliptin in these patients. This real-world study included patients with type 2 diabetes mellitus (T2DM), who were poorly glycemic controlled on premixed insulin therapy and were subsequently added vildagliptin. The control group consisted of patients who only had their insulin doses adjusted without adding vildagliptin, matched for age, diabetic duration, HbA1c, and BMI. All patients underwent FGM, glycated hemoglobin(HbA1c), and glycated albumin(GA) measurements at baseline and three months after the treatment adjustment. Patients receiving vildagliptin treatment demonstrated significant reductions in HbA1c and GA levels (P<0.001 and P=0.009, respectively). The vildagliptin group exhibited a remarkable decrease in the mean amplitude of glycemic excursion (MAGE) (8.58 ± 0.36 vs. 6.62 ± 0.47, P<0.001), along with notable reductions in mean blood glucose (MBG) (10.7 ± 0.34 vs. 8.82 ± 0.39, P<0.001) and time above the target range (TAR) (52.60 ± 3.44 vs. 31.59 ± 4.31, P<0.001) compared to the control group. Moreover, there were notable improvements in the duration spent within the target range (TIR) (45.64 ± 3.33 vs. 64.22 ± 4.00, P<0.001), along with increases in the areas under the curve (AUC) for blood glucose levels above 4.4 (426.82 ± 83.19 vs. 892.16 ± 185.27, P=0.018) and 3.9 (213.81 ± 47.20 vs. 454.77 ± 103.21, P=0.029). Hourly mean blood glucose levels over a 2-week period monitored by FGM indicated lower blood glucose levels in the vildagliptin group, particularly after dinner (P=0.022). Vildagliptin added to premixed insulin effectively lowers blood glucose levels and reduces glycemic variability in patients with type 2 diabetes mellitus. https://clinicaltrials.gov, identifier NCT04847219.

Purpose: Hyperuricemia has traditionally been associated with obesity and dyslipidemia. However, the relationship between waist circumference (WC) and hyperuricemia in normal-weight men is still unclear, particularly regarding the roles of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). The aim of this research was to explore the mediating roles of TG and HDL-C in the association between WC and hyperuricemia in normal-weight men. Methods: A retrospective observational study was conducted among normal-weight men (18.5 <= BMI < 24 kg/m(2)) aged >= 18 years who underwent health checkups in Nanjing from 2021- 2023. Relationships between WC, blood lipids, and hyperuricemia were investigated by multivariable regression models and mediation analysis. Results: We enrolled 35,984 participants, with an overall hyperuricemia prevalence of 24.2%. The research found a significant positive association between WC and hyperuricemia in normal-weight men (P < 0.001). For hyperuricemia across rising WC quartiles, with WC divided as follows: Q1 (59 <= WC < 77 cm), Q2 (77 <= WC < 81 cm), Q3 (81 <= WC < 85 cm), and Q4 (85 <= WC <= 107 cm), the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.00 (reference), 1.09 (1.01, 1.18), 1.26 (1.15, 1.37), and 1.34 (1.22, 1.46), respectively (all P < 0.001). The mediation analysis indicated that WC had a significant total effect on hyperuricemia (Coefficient = 0.0046, 95% CI: 0.0028, 0.0070, P < 0.001), with significant indirect effects mediated through TG and HDL-C, contributing mediation proportions of 22.3% and 18.3%, respectively (both P < 0.05). Conclusion: Elevated WC is associated with an increased likelihood of hyperuricemia in normal-weight men. TG and HDL-C play substantial mediating roles in this association. These findings suggest that monitoring WC and lipid profiles in normal-weight men could help identify those at higher risk of hyperuricemia, even in the absence of general obesity.

Intensive insulin therapy has been extensively used to control blood glucose levels because of its ability to reduce the risk of chronic complications of diabetes. According to current guidelines, intensive glycemic control requires individualized glucose goals rather than as low as possible. During intensive therapy, rapid blood glucose reduction can aggravate microvascular and macrovascular complications, and prolonged overuse of insulin can lead to treatment-induced neuropathy and retinopathy, hypoglycemia, obesity, lipodystrophy, and insulin antibody syndrome. Therefore, we need to develop individualized hypoglycemic plans for patients with diabetes, including the time required for blood glucose normalization and the duration of intensive insulin therapy, which deserves further study.

Objective. The mechanism of steroidogenesis and spermatogenesis impairment in men with type 2 diabetes remains unclear. We aimed to explore the local changes of steroidogenesis and spermatogenesis in the testis of db/db mice. Research Design and Methods. We performed single-cell RNA sequencing analysis in the testis of db/db and C57BL/6J mice. The differentially expressed genes were then confirmed by real-time PCR. The histopathological characteristics of testis in db/db mice and C57BL/6J control were also performed. Results. The 20-week-old db/db mice had significantly higher blood glucose and body weight (both p<0.001). The serum testosterone levels (4.4 ± 0.8 vs. 9.8 ± 0.7 ng/ml, p=0.001) and weight of the testis (0.16 ± 0.01 vs. 0.24 ± 0.01 g, p<0.001) were significantly lower in db/db mice than that in C57BL/6J controls. db/db mice had a lower cross-sectional area of seminiferous tubules and thickness of the cell layer (both p<0.05). The numbers of Sertoli cells and Leydig cells decreased in db/db mice (both p<0.01). Single-cell RNA sequencing analysis showed that compared with the control group, the percentage of spermatogonia was significantly higher in the db/db mouse (p<0.001), while the proportions of spermatocytes, round and elongating spermatids, and sperms were all lower in the db/db mouse (p all<0.001). The most differentially expressed genes were found in round spermatids (n = 86), which were not found in spermatogonia, spermatocyte, and sperm. Igfbp5 was the most significantly decreased gene in Leydig cells of the db/db mouse, while the expression of Cd74, H2-Aa, and H2-Eb1 was elevated. Ccl7 and Ptgds were the most significantly increased and decreased genes in Sertoli cells of the db/db mouse. Conclusions. The present study indicates spermiogenesis and steroidogenesis defects in db/db mice. The mechanism of steroidogenesis impairment in the testis of db/db mice deserves further investigation.

BACKGROUND Insulin antibodies (IAs) affect blood glucose control in patients receiving insulin therapy. AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus (T2DM). METHODS This cross-sectional, retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy. All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array. RESULTS A total of 1863 patients were enrolled. There were 902 (48.4%) patients who had positive IAs (IA level > 5%), with a mean IA level of 11.06% (10.39%-11.72%). IA levels were positively correlated with high fasting blood glucose (odds ratio = 1.069, P < 0.001). The proportion of positive IAs was lowest in patients using glargine only (31.9%) and highest in patients using human insulin only (70.3%), P < 0.001. The IA levels in patients using sulfonylureas/glinides (8.3%), metformin (9.6%), and dipeptidyl peptidase-4 inhibitors (8.2%) were all lower than in patients without these drugs (all P < 0.05). CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies, and IA antibody levels are associated with blood glucose control. Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

Background: Roxadustat is commonly used to treat renal anemia. However, the potential effects of roxadustat on metabolism and organs other than the kidneys have recently attracted increased attention. Objective: This study aimed to examine the regulatory effects of roxadustat on thyroid hormones and blood lipid metabolism in patients with end-stage kidney disease (ESKD) undergoing hemodialysis. Methods: Eighty ESKD patients on hemodialysis and taking roxadustat were enrolled. Hemoglobin, thyroid hormones (TSH, FT3, FT4), and blood lipid profiles (TC, LDL-C, TG, HDL-C) were assessed before and after treatment. Changes in these parameters were compared, and relevant causative factors were analyzed. Results: Roxadustat significantly increased Hb, lowered TSH, FT4, TC, and LDL-C levels (all P<0.001). Patients were categorized into three groups based on post-treatment TSH inhibition percentage: Q1(≥70%), Q2(30%-70%), Q3(≤30%). Pre-treatment TSH decreased with reduced TSH inhibition (P<0.05). Post-treatment, TC, LDL-C, TSH, FT3, and FT4 increased with reduced TSH inhibition (all P<0.05).TC and LDL-C significantly decreased post-treatment in Q1 and Q2 (P<0.05). Correlation analysis showed a positive correlation between ΔTSH and pre-treatment TSH levels (r=0.732, P<0.001). The proportion of patients with ≥70% TSH inhibition increased with higher pre-treatment TSH levels (P for trend <0.05). ΔLDL-C and ΔTSH were positively correlated (r=0.278, P<0.05), with ΔTSH identified as an influencing factor in multiple linear regression (β=0.133, 95% CI [0.042, 0.223], P<0.05). Conclusion: Roxadustat effectively improves anemia in ESKD patients while inhibiting TSH and FT4 secretion and reducing TC and LDL-C levels. Decreases in TSH levels correlate with baseline TSH levels, and lowered blood lipid levels are associated with decreased TSH levels.

Objective To create a nomogram-based model to estimate the Chinese population's 5-year risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods We randomly divided 7582 participants into two groups in a 7:3 ratio: one group was assigned to work with the training set, which consisted of 5307 cases, and the other group was assigned to validate the model using 2275 cases. The least absolute shrinkage and selection operator model was employed to ascertain the variables with the highest correlation among all potential variables. A logistic model was constructed by incorporating these selected variables, which were subsequently visualized using a nomogram. The discriminatory ability, calibration, and clinical utility of the model were assessed using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results During the 5-year follow-up, 1034 (13.64%) total participants were newly diagnosed with MASLD. Using eight variables (gender, body mass index, waist, hemoglobin, alanine aminotransferase, uric acid, triglycerides, and high-density lipoprotein), we built a 5-year MASLD risk prediction model. The nomogram showed an area under the ROC of 0.795 (95% CI: 0.779–0.811) in the training set and 0.785 (95% CI: 0.760–0.810) in the validation set. The calibration curves revealed a 5-year period of agreement between the observed and predicted MASLD risks. DCA curves illustrated the practicality of this nomogram over threshold probability profiles ranging from 5% to 50%. Conclusion We created and tested a nomogram to forecast the risk of MASLD prevalence over the next 5 years.