Previous studies have showed that the apoptosis of vascular smooth muscle cells (VSMCs) underlies the mechanism of pathological calcifications in patients with chronic kidney disease (CKD). SET domain-containing protein 8 (SET8), as an efficient protein has been reported to modulate cell apoptosis in hepatocellular carcinoma cell, esophageal squamous cell and neuronal cell through regulating pathological processes, such as cell-cycle progression and transcription regulation. However, whether SET8 is involved in high phosphorus induced vascular calcification by mediating apoptosis remains undefined. Here, we reported that SET8 was located both in nucleus and cytoplasm, and significantly downregulated in calcification models. SET8 deficiency promoted the apoptosis of VSMCs, which was indicated by the increased Bax/Bcl-2 and cleaved caspase-3/total caspase-3 ratios. Mechanistically, PI3K/Akt pathway was mediated by SET8 and inhibition of PI3K/Akt signaling pathway by giving LY294002 or transfecting Akt phosphorylation inactivated mutation plasmid increased apoptosis and calcification. Akt phosphorylation constitutively activated mutation could reduce apoptosis and calcification of VSMCs. Furthermore, exogenous overexpression of SET8 could reverse the effect of PI3K/Akt inhibition on the apoptosis and calcification of VSMCs. In summary, our researches suggested that SET8 overexpression ameliorated high phosphorus induced calcification of vascular smooth muscle cells via activating PI3K/Akt mediated anti-apoptotic effects.
Rationale: Anti-glomerular basement membrane (anti-GBM) disease has been reported to coexist with other immunemediated glomerular disorders, including antineutrophil cytoplasmic autoantibody positive glomerulonephritis and membranous glomerulopathy. It is well known that anti-GBM disease often manifests as type I crescentic glomerulonephritis on renal biopsy. However, concurrent cases of both type I crescentic glomerulonephritis and IgA nephropathy are rare.Patient concerns: We report the case of a 40-years-old woman with microscopic hematuria, mild proteinuria and an immunocompromised status. Laboratory data revealed serum creatinine showed progressive progress, suddenly rising from the normal range to 316.2μmol/L within 4 months. The CD4 lymphocyte count was 0.274 × 10 9 /L (reference value 0.35-1.82 × 10 9 /L). The anti-GBM antibody titer was 192.4 IU/mL (reference range: <20 RU/mL).Diagnoses: Renal biopsy was performed after admission. The pathological diagnosis was type I crescentic glomerulonephritis, IgA nephropathy, and clinical anti-GBM disease. Interventions:The patient was seriously ill on admission and progressed rapidly. Combined with poor immune function, we immediately initiated high-frequency plasma exchange (PE). In addition, to avoid rebound of antibody levels, PE was performed for 5 times. Follow-up treatment was combined with standard-dose corticosteroids and cyclophosphamide.Outcomes: The patient was followed up for 1 year. On the last visit, her serum creatinine decreased to 103.5μmol/L, anti-GBM antibody remained negative, and proteinuria and hematuria disappeared.Lessons: This case illustrates that when crescentic nephritis or anti-GBM disease is combined with other immune diseases, especially when the immune function is extremely low, if the application of high-dose steroid shocks may induce fatal infections, to some extent high frequency PE has certain advantages.Abbreviations: anti-GBM = anti-glomerular basement membrane, ANCA = antineutrophil cytoplasmic antibody, GBM = glomerular basement membrane, IgG = immunoglobulin G, PE = plasma exchange.
Objectives This study’s objective was to explore the possibility of clinical evaluation of digestive system’s cancer with or without AKI patients’ cardiac function measured by impedance cardiography (ICG, Bioz. Cardio Dynamics, USA); then, try to analyze the possible reason of cardiac function changing, and to approach the independent risk factors for it. Methods Patients who were admitted to the Fourth hospital of Hebei Medical University, China between May 1st, 2019 and February 15th, 2022 were involved. A total of 51 patients with digestive system’s cancer with AKI or without AKI (31 men and 20 women, mean age 61.1 ± 10.9 year) were evaluated to routine ICG. Of the total, 19 patients were assessed to both ultrasound cardiography (UCG) and ICG. Result There were significant positive correlation with the cardiac function parameters, such as cardiac output (CO), cardiac index (CI), stroke volume (SV), left cardiac work index (LCWI) and ejection fraction (EF), measured by ICG and UCG. The relationship was observed between COICG and COUCG (r = 0.707, P = 0.001); CIICG and CIUCG (r = 0.718, P = 0.001); SVICG and SVUCG (r = 0.837, P < 0.001); LCWIICG and EFUCG (r = 0.540, P = 0.017). The cardiac function parameters measured by ICG were statistically significant between cancer with AKI and without AKI patients (P < 0.05). A multivariate analysis revealed that AKI had independent effects on digestive system’s cancer patients’ cardiac function. Conclusions ICG and UCG methods were significant positive correlation with the cardiac function of digestive system’s cancer patients with or without AKI; the cardiac function of digestive system’s cancer with AKI was worse than that of without AKI patients; AKI was the independent risk factor for cardiac function in digestive system’s cancer patients.
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