ABSTRACT
Objective:To investigate the expression of serum heat shock protein 70 (HSP70), soluble programmed death protein 1 (sPD-1), and 25-hydroxy vitamin D 3 in hepatitis B associated liver cirrhosis (HBLC) combined with type 2 diabetes mellitus (T2DM) and their value in prognostic prediction. Methods:The clinical data of 97 patients with HBLC combined with T2DM (HBLC combined with T2DM group), 105 patients with HBLC (HBLC group) and 118 patients with T2DM (T2DM group) from June 2018 to November 2019 in Zhejiang Putuo Hospital were prospectively analyzed. The serum levels of HSP70, sPD-1 and 25-hydroxy vitamin D 3 were compared among 3 groups, and the correlation between above serum indexes and liver function indexes, blood sugar indexes were analyzed. The liver function indexes included alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the blood sugar indexes included fasting blood glucose (FBG) and glycosylated hemoglobin (HbA 1c). According to the prognosis 6 months later, the patients with HBLC combined with T2DM were divided into poor prognosis (28 cases) and good prognosis (69 cases), and the HSP70, sPD-1, 25-hydroxy vitamin D 3 and liver function Child-Pugh classification were compared. The predictive value of serum HSP70, sPD-1 and 25-hydroxy vitamin D 3 on prognosis in patients with HBLC combined with T2DM was analyzed by receiver operating characteristic (ROC) curve. Results:The HSP70 and sPD-1 in HBLC combined with T2DM group were significantly higher than those in HBLC group and T2DM group: (4.28 ± 1.19) μg/L vs. (2.27 ± 0.76) and (2.40 ± 0.84) μg/L, (7.86 ± 2.45) ng/L vs. (4.23 ± 1.62) and (3.85 ± 1.27) ng/L, the 25-hydroxy vitamin D 3 was significantly lower than that in HBLC group and T2DM group: (13.62 ± 3.96) μg/L vs. (18.63 ± 6.11) and (17.45 ± 4.36) μg/L, and there were statistical differences ( P<0.05); there were no statistical differences between HBLC group and T2DM group ( P>0.05). The Pearson correlation analysis result showeds that HSP70 and sPD-1 were positively correlated with ALT, AST, FBG and HbA 1c ( P<0.01), the 25-hydroxy vitamin D 3 was negatively correlated with ALT, AST, FBG and HbA 1c ( P<0.01) in patients with HBLC combined with T2DM. In patients with HBLC combined with T2DM, the HSP70, sPD-1 and rate of Child-Pugh classification B in patients with poor prognosis were significantly higher than those in patients with good prognosis: (6.03 ± 1.63) μg/L vs. (3.57 ± 1.02) μg/L, (9.86 ± 1.59) ng/L vs. (7.05 ± 2.62) ng/L and 71.43% (20/28) vs. 30.43% (21/69), the 25-hydroxy vitamin D 3 was significantly lower than that in patients with good prognosis: (9.26 ± 3.02) μg/L vs. (15.39 ± 5.84) μg/L, and there were statistical differences ( P<0.01 or <0.05). The ROC curve analysis result showed that the area under curve of HSP70, sPD-1 combined with 25-hydroxy vitamin D 3 in predicting prognosis was the highest in patients with HBLC combined with T2DM, which was 0.890, with a sensitivity of 89.29% and a specificity of 79.71%. Conclusions:The levels of serum HSP70 and sPD-1 in patients with HBLC combined with T2DM increase, and the level of 25-hydroxy vitamin D 3 decreases. There is a good linear relationship with liver function and blood glucose. Early combined detection of the above serum levels can provide new ideas for clinical implementation of symptomatic treatment and prognosis prediction.
ABSTRACT
To investigate changes in the angiotensin converting enzyme 2 (ACE2) and angiotensin (1-7) [Ang (1-7)] and to explore the role of ACE2-Ang (1-7)-Mas receptor axis in hypertension with heart failure with preserved ejection fraction (HFPEF). Methods: A total of 70 patients with primary hypertension and preserved left ventricular ejection fraction (LVEF>50%) were recruited and patients were divided into a hypertension group (HBP) and a heart failure with preserved ejection fraction group (HFpEF) according to the diagnostic criteria of HFpEF. Thirty-five healthy participants were selected randomly as a control group. Enzyme linked immunosorbent assays (ELISA) method was used to detect concentration of Ang (1-7), ACE2, angiotensin II (Ang II), brain natriuretic peptide (BNP) in plasma. Male Sprague- Dawley (SD) rats was randomly divided into 2 groups: An HFpEF group (n=16) and a sham group (n=8). Rats (n=8) in the AAC group were given Ang (1-7) [0.5 mg/(kg.d), intraperitoneally] for 6 weeks, and the rest were given equal dose normal saline. Then all the rats were killed, and the hearts were taken out for hematoxylineosin (HE) staining. The protein expressions of angiotensin converting enzyme (ACE), ACE2, and Mas receptor were detected by Western blot. Results: The BNP and Ang II were significantly increased in the HBP group and the HFpEF group compared with the control group (P0.05), whereas those levels were significantly increased in the HFpEF group compared with the HBP group and control group (P0.05). Conclusion: ACE2 and Ang (1-7) are important predictive factors for the severity of heart failure and myocardial remodeling of HFpEF with hypertension; ACE2-Ang (1-7)-Mas receptor axis may play a protective role in preventing myocardial remodeling in HFpEF with hypertension.