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Abstract Background Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 2 diabetes mellitus, and its mechanisms are complex and poorly understood. Despite growing evidence suggesting that ferroptosis plays a significant role in cardiovascular disease, it has been less extensively studied in DCM. Fibroblast growth factor 21 (FGF21), whose mechanism of action is closely related to ferroptosis, is widely utilized in studies focused on the prevention and treatment of glucolipid metabolism-related diseases and cardiovascular diseases. Objective To confirm the significant role of ferroptosis in DCM and to investigate whether FGF21 improves DCM by inhibiting ferroptosis and elucidating its specific molecular mechanisms. Methods The animal DCM models were established through high-fat feeding combined with streptozotocin injection in C57BL/6J mice or by db/db mice, and the diabetic cardiomyocyte injury model was created using high glucose and high fat (HG/HF) culture of primary cardiomyocytes. Intervention modeling of FGF21 were performed by injecting adeno-associated virus 9-FGF21 in mice and transfecting FGF21 siRNA or overexpression plasmid in primary cardiomyocytes. Results The findings indicated that ferroptosis was exacerbated and played a significant role in DCM. The overexpression of FGF21 inhibited ferroptosis and improved cardiac injury and function, whereas the knockdown of FGF21 aggravated ferroptosis and cardiac injury and function in DCM. Furthermore, we discovered that FGF21 inhibited ferroptosis in DCM by directly acting on ferritin and prolonging its half-life. Specifically, FGF21 binded to the heavy and light chains of ferritin, thereby reducing its excessive degradation in the proteasome and lysosomal-autophagy pathways in DCM. Additionally, activating transcription factor 4 (ATF4) served as the upstream regulator of FGF21 in DCM. Conclusions The ATF4-FGF21-ferritin axis mediates the protective effects in DCM through the ferroptosis pathway and represents a potential therapeutic target for DCM.

Background Cell division cycle protein 45 (CDC45) has been demonstrated to play vital roles in the progression of various malignancies. However, the clinical significance of CDC45 in gastric cancer (GC) remains unreported. Method In this study, we employed the TCGA database and the TCGA & GTEx dataset to compare the mRNA expression levels of CDC45 between gastric cancer tissues and adjacent or normal tissues (p < 0.05 was considered statistically significant), which was further validated in multiple datasets including GSE13911, GSE29272, GSE118916, GSE66229, as well as RT-qPCR. Furthermore, we harnessed the Human Protein Atlas (HPA) to evaluate the protein expression of CDC45, which was subsequently verified through immunohistochemistry (IHC). To ascertain the diagnostic utility of CDC45, receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were calculated in TCGA database, and further validated it in TCGA & GTEx and GSE66229 datasets. The Kaplan–Meier method was used to reveal the prognostic importance of CDC45 in The Cancer Genome Atlas (TCGA) database and authenticated through the GSE66229, GSE84433, and GSE84437 datasets. Through cBioPortal, we identified co-expressed genes of CDC45, and pursued enrichment analysis. Additionally, we availed gene set enrichment analysis (GSEA) to annotate the biological functions of CDC45. Results Differential expression analysis revealed that CDC45 was significantly upregulated at both the mRNA and protein levels in GC (all p < 0.05). Remarkably, CDC45 emerged as a promising prognostic indicator and a novel diagnostic biomarker for GC. In a comprehensive the drug susceptibility analysis, we found that patients with high expression of CDC45 had high sensitivity to various chemotherapeutic agents, among which 5-fluorouracil, docetaxel, cisplatin, and elesclomol were most evident. Furthermore, our findings suggested a plausible association between CDC45 and immune cell infiltration. Enrichment analysis revealed that CDC45 and its associated genes may play crucial roles in muscle biofunction, whereas GSEA demonstrated significant enrichment of gene sets pertaining to G protein-coupled receptor ligand binding and G alpha (i) signaling events. Conclusion Our study elucidates that upregulation of CDC45 is intricately associated with immune cell infiltration and holds promising potential as a favorable prognostic marker and a novel diagnostic biomarker for GC.

BackgroundPrediabetes is associated with an increased risk of cardiovascular diseases and all-cause mortality. Rare research in China has evaluated the prevalence of prediabetes among children and adolescents using the HbA1c criterion or the combined FPG-or-HbA1c diagnostic criterion, and researchers paid no attention to the distributions of blood glucose in Shenzhen, especially for juveniles.MethodsWe conducted a school-based cross-sectional study based on the first-year students from 17 primary, middle, and high schools. Prediabetes was defined as FPG of 5.6–6.9 mmol/L or HbA1c of 5.7%–6.4%. The crude and standardized prevalence of prediabetes with 95% confidence interval (95% CI) was estimated.ResultsA total of 7519 participants, aged 6 to 17 years, were included. For all subjects, the crude prevalence (95% CI) of prediabetes was 1.49% (1.21–1.77), 8.72% (8.08–9.36), and 9.80% (9.13–10.47) by the FPG-only, HbA1c-only, and FPG-or-HbA1c criteria, respectively. Based on the 2010 Shenzhen census population, the standardized prevalence was 1.56% (males 1.85%, females 1.19%), 11.05% (males 11.47%, females 10.53%), and 12.19% (males 13.01%, females 11.15%) by the corresponding criteria. The proportion of prediabetes was higher for males than females, and the prevalence decreased with grade for males but increased for females. The association of BMI and prediabetes was U-shaped curve, indicating higher rates of prediabetes for underweight and obesity people.ConclusionThe blood glucose status of children and adolescents in Shenzhen is worrisome, and the early detection and management of prediabetes are imperative.

Background: Rapid and accurate diagnosis of HIV-positive patients with Talaromyces marneffei (T. marneffei) infections remains challenging. A 60-year-old woman came to our inpatient department presenting with hematuria, abdominal pain, and diarrhea for one week. The patient had a past medical history of Acquired Immune Deficiency Syndrome (AIDS). The patient's stool was watery and the color of soy sauce. The patient was without fever, cough, and skin lesions. Methods: The blood routine was performed with a Mindray BC-6900 hematology analyzer. Results: Blood routine showed leukocytosis with neutrophilia and basophils and the WBC/DIFF scattergram showed a cluster of neutrophils connected with a monocyte and lymphocyte cluster and an additional cluster of immature granulocytes and heterotypic lymphocytes or primitive cells. Surprisingly, the peripheral blood film evaluation revealed small round-to-ovoid yeast cells within the cytoplasm of neutrophils. A T. marneffei infection was suspected and anti-fungal therapy was initiated. The patient's diarrhea improved after treatment with amphotericin B for two days. A second blood routine showed a normal number of leukocytes and basophils and a diminished cluster of immature granulocytes and heterotypic lymphocytes or primitive cells. After one week, blood cultures had grown T. marneffei. Conclusions: The WBC/DIFF scattergram obtained from a Mindray BC-6900 analyzer provided significant hints to enhance diagnosis of T. marneffei when combined with results of a peripheral blood smear. [ABSTRACT FROM AUTHOR]