ABSTRACT
Background: ccRCC, also known as clear cell renal cell carcinoma, is a cancer that is highly metabolically active and has a strong connection with the immune system. The objective of this research was to investigate the correlation between pathways associated with metabolism, diabetes, immune infiltration, and their impact on the prognosis of ccRCC. Method: We conducted an extensive examination utilizing ssGSEA, ESTIMATE algorithm, WGCNA, and GSVA for gene set enrichment analysis, gene co-expression network analysis, and gene set variation analysis. An established prognostic model, utilizing immune-related WGCNA findings, was evaluated for its association with clinical characteristics and the tumor microenvironment (TME). Result: The ssGSEA effectively categorized ccRCC into groups based on low and high metabolism. Strong associations were observed between scores related to metabolism and immune scores, ESTIMATE scores, stromal scores, and gene expression related to HLA. The analysis conducted by WGCNA revealed a module called the 'yellow module' that exhibited a significant correlation with the infiltration of immune cells and the survival rates of patients. A risk model was developed, demonstrating reliable predictive performance for patient survival outcomes. The risk model also correlated significantly with immune scores and HLA-related gene expressions, suggesting potential immune evasion mechanisms. The analysis of mutations in TCGA data revealed the mutational patterns of ccRCC, and there was a significant correlation between the risk score and clinical characteristics. The GSVA analysis revealed a notable enrichment of pathways associated with cancer in patients at high risk. Finally, in order to evaluate the role of CX3CL1 in renal cell carcinoma cells, we then performed the cell proliferation assays. The results demonstrated that the over expression of CXCL1 could promote the cell proliferation ability in renal cell carcinoma cells. Conclusion: Our findings provide a novel perspective on the interactions between diabetes, metabolic pathways, and the immune landscape in ccRCC. The predictive value of the prognostic model established in this research has the potential to guide the development of new therapeutic and prognostic approaches for patients with ccRCC.
ABSTRACT
OBJECTIVES: To investigate serum 25-hydroxyvitamin D (25[OH]D) levels in patients with diabetic nephropathy, analyse the relationship between 25(OH)D and clinical indexes, and identify risk factors for vitamin D deficiency in diabetic nephropathy. METHODS: Patients with diabetic nephropathy were sequentially enrolled and grouped according to diabetic nephropathy stage. Serum 25(OH)D levels were measured. A control group of healthy subjects was used for comparison. RESULTS: Out of 240 patients with diabetic nephropathy and 60 healthy controls, 25(OH)D levels were lower in diabetic nephropathy patients than in controls, and showed a gradually decreasing trend with diabetic nephropathy stage. Serum 25(OH)D levels were significantly correlated with age, sex, diabetes history, body mass index, systolic blood pressure, albumin excretion rate (AER), estimated glomerular filtration rate, fasting blood glucose, glycosylated haemoglobin (HbA1c), haemoglobin, serum albumin, creatinine clearance rate, blood urea nitrogen and complicated diabetic retinopathy. Moreover, age, body mass index, AER, haemoglobin, and HbA1c were independent risk factors of 25(OH)D deficiency in diabetic nephropathy. CONCLUSIONS: Vitamin D deficiency is prevalent in patients with diabetic nephropathy and increases in severity with diabetic nephropathy progression. Age, obesity, glucose level and renal function largely affect 25(OH)D deficiency in diabetic nephropathy.
Subject(s)
Diabetic Nephropathies/complications , Diabetic Nephropathies/epidemiology , Vitamin D Deficiency/complications , Vitamin D Deficiency/epidemiology , Case-Control Studies , Demography , Diabetic Nephropathies/blood , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Risk Factors , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/bloodABSTRACT
BACKGROUND AND AIMS: More attention has recently been focused on auditory impairment of young type 1 diabetics. This study aimed to evaluate auditory function of young type 1 diabetics and the correlation between clinical indexes and hearing impairment. METHODS: We evaluated the auditory function of 50 type 1 diabetics and 50 healthy subjects. Clinical indexes were measured along with analyzing their relation of auditory function. RESULTS: Type 1 diabetic patients demonstrated a deficit with elevated thresholds at right ear and left ear when compared to healthy controls (p <0.01). The elevated auditory threshold was significantly related with HDL-cholesterol, diabetes duration, and systemic blood pressure (p <0.05). Moreover, latencies of right ear (wave III, V and interwave I-V) and left ear (wave III, V and interwave I-III, I-V) in diabetic group significantly increased compared to those in control subjects (p <0.01). Auditory brainstem response was significantly related with GHbA1C and microalbuminuria (p <0.01). Furthermore, distortion product evoked otoacoustic emissions (DPOAE) of diabetes group were statistically significant in right ears at 4.0, 6.0 kHz and in left ears at 4.0, 6.0, 8.0 kHz (p <0.01) compared with those of controls. Diabetic patients demonstrated lower amplitude responses of the right ear than the left ear at 8.0 kHz. Only triglyceride was positively correlated to the hearing impairment defined by DPOAE (p <0.01). There was no significance of transient evoked otoacoustic emissions (TEOAE) between groups. TEOAE was associated with age and GHbA1C (p <0.01). CONCLUSIONS: Type 1 diabetics exerted higher auditory threshold, slower auditory conduction time and cochlear impairment. HDL-cholesterol, diabetes duration, systemic blood pressure, microalbuminuria, GHbA1C, triglyceride, and age may affect the auditory function of type 1 diabetics.