Effects of sustained low-efficiency dialysis combined with hemoperfusion on routine blood indicators and inflammatory factors in patients with sepsis-induced acute kidney injury / 中国基层医药

Objective:To investigate the effects of sustained low-efficiency hemodialysis combined with hemoperfusion on routine blood indicators and inflammatory factors in patients with sepsis-induced acute kidney injury.Methods:Eighty-six patients with sepsis-induced acute kidney injury who received treatment in Yantai Laiyang Central Hospital from April 2018 to April 2021 were included in this study. They were randomly divided into an observation group and a control group, with 43 cases in each group. All patients received conventional supportive treatment. The control group received continuous renal replacement therapy and the observation group received sustained low-efficiency dialysis combined with hemoperfusion. Before and after treatment, routine blood indicators [hemoglobin (Hb), white blood cell (WBC) count, platelet (PLT) count, albumin (Alb)], inflammatory factors [interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), procalcitonin PCT)], renal function indicators [serum creatinine (Scr), blood urea nitrogen (BUN)], The Acute Physiology and Chronic Health Evaluation (APACHE) II score, length of hospital stay, and 28-day mortality rate were compared between the two groups.Results:Before treatment, there were no significant differences in Hb, WBC count, PLT count, Alb, IL-6, CRP, TNF-α, PCT, Scr, BUN, and APACHE II score between the two groups ( t = 0.04, 0.95, 0.23, 0.67, 1.54, 0.75, 0.98, 0.23, 1.04, 0.44, 0.07, all P > 0.05). After treatment, serum levels of Hb and Alb in each group were significantly increased compared with those before treatment. After treatment, serum levels of Hb and Alb in the observation group were (105.29 ± 15.80) g/L, (39.25 ± 7.87) g/L, respectively, which were significantly higher than (98.55 ± 12.93) g/L and (33.38 ± 7.29) g/L in the control group ( t = 2.16, 3.58, both P < 0.05). After treatment, WBC count, PLT count, IL-6, CRP, TNF-α, PCT, Scr, and BUN levels, and APACHE II score in each group were significantly decreased compared with those before treatment. After treatment, WBC count, PLT count, IL-6, CRP, TNF-α, PCT, Scr, and BUN levels, and APACHE II score in the observation group were (10.28 ± 1.87) × 10 9/L, (129.32 ± 14.79) × 10 9/L, (59.00 ± 12.77) μg/L, (22.41 ± 5.01) mg/L, (28.41 ± 4.77) μg/L, (18.41 ± 2.78) μg/L, (162.01 ± 21.04) μmol/L, (7.38 ± 1.17) mmol/L, (11.28 ± 3.60) points, respectively, which were significantly lower than (12.32 ± 2.27) × 10 9/L, (137.39 ± 18.30) × 10 9/L, (79.35 ± 14.36) μg/L, (29.31 ± 6.37) mg/L, (34.33 ± 5.38) μg/L, (22.32 ± 3.35) μg/L, (184.06 ± 24.03) μmol/L, (9.87 ± 1.66) mmol/L, (14.65 ± 3.38) points in the control group ( t = 4.54, 2.24, 6.94, 5.58, 5.39, 5.89, 4.52, 8.03, 4.47, all P < 0.05). The length of intensive care unit stay in the observation group was significantly shorter than that in the control group [(11.63 ± 2.18) days vs. (14.07 ± 2.71) days, t = 4.60, P < 0.05]. There was no significant difference in 28-day mortality rate between the two groups ( χ2 = 1.36, P > 0.05). Conclusion:Sustained low-efficiency dialysis combined with hemoperfusion is effective on sepsis-induced acute kidney injury. The combined therapy can improve routine blood indicators, inhibit inflammatory reactions, promote renal function recovery, and decrease the mortality rate to a certain degree.

TNFα and IL-1ß in the synovial fluid facilitate mucosal-associated invariant T (MAIT) cell migration.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affect the joints and inflammatory cell migration into inflamed articular sites contribute to this disease. Among the inflammatory cells, human mucosal-associated invariant T (MAIT) cells were recently recognized as critical cellular component with a pathological role in RA. However, their migratory characteristics are poorly understood. The aim of this study was to determine whether human MAIT cells preferentially traffick to inflamed synovial sites in rheumatoid arthritis patients and to elucidate the underlying mechanism. First, we found that TNFα and IL-1ß were elevated in synovial fluid (SF) of RA patients, which resulted in increased expression of E-selectin, ICAM-1 and V-CAM-1 on blood vessel endothelial cells. To understand whether TNFα and IL-1ß in the SF facilitated MAIT cell migration, we analyzed CD161+ TCRα7.2+ MAIT and other CD3+ T cells for differences in migratory capacity. Collectively, our results demonstrate that TNFα and IL-1ß in the SF facilitated MAIT cell migration dependent on expression of selectin ligand, sialyl LewisX (sLeX) and CCR6 on MAIT cells. We also showed that MAIT cells in the SF from RA patients equipped upregulated sLeX compared to the peripheral blood of RA patients and healthy persons, which suggest that TNFα and IL-1ß mediated expression of E-selectin preferentially attract sLeX mediated MAIT cell migration into the SF of RA patients.

Inhibition of AKT/FoxO3a signaling induced PUMA expression in response to p53-independent cytotoxic effects of H1: A derivative of tetrandrine.

PUMA (p53 unregulated modulator of apoptosis), a BH3-only Bcl-2 family member, can be induced by p53-dependent and p53-independent manners. It plays an important role as regulator of cellular apoptosis. Herein, we evaluate the effects of H1 (a derivative of tetrandrine) on induction of PUMA and underlie its potential mechanism in p53-independent cytotoxic response. Anti-proliferative activity and evidently cytotoxic activity of H1 were observed in wild-type and p53 null cells. Further studies demonstrated that H1 resulted in an increase of cleaved PARP, decease of survivin and elevation of p-H2AX. What is more, H1 significantly induced PUMA expression in a concentration- and time-dependent manner and caused an increase of Bax/Bcl-2 ratio in p53 null cells. Of note, knockdown of PUMA attenuated cytotoxic activity of H1. Further studies demonstrated that inhibition of AKT/FoxO3a signaling contributed to H1-mediated PUMA induction. Targeted suppression of AKT/FoxO3a signaling by siRNA could overcome H1-mediated PUMA induction. In addition, H1 significantly suppressed NF-κB activity and caused an increase of early apoptotic and late apoptotic cells, and elevated caspase-3 activity. Taken together, we found that inhibition of AKT/FoxO3a signaling may contribute to H1-mediated PUMA induction, suggesting that inhibition of AKT/FoxO3a signaling result in PUMA expression in response to p53-independent cytotoxic effects of H1.

The relationship between pancreatic ischemia and cytokines in rats with acute pancreatitis / 中国普通外科杂志

Objectives To investigate the r el ationship between pancreatic ischemia and cytokines released in rats with acute pancreatitis(AP). Methods 20 acute edematous pancreatitis(AEP) and 20 acute necrotizing pancreatits(ANP) rat models wer e induced by injection of sodium taurocholate into the pancreatic duct, another 10 normal rats were used as control. At 12 hours after the induction of AP, 10 r ats in each group were sacrificed, blood and pacreatic tissue samples were taken for measurement of TNF-? and IL-10 levels. The pathological study of pancre as was performed, and pancreatic blood flow(PBF) was measured by Doppler ultraso und instrument.Results The TNF -? and IL-10 levels in serum and pancreatic tissue increased after the induction of AP, IL-10 levels elevated more significantly in AEP rats, TNF-? levels e levated more significantly in ANP rats. PBF reduced in AP rats, and the amplitud e of PBF measured by Doppler ultrasound was closely correlated with serum and ti ssue TNF-?, IL-10 levels, inflammation, hemorrhage and necrosis scores.Conclusion The reduction of PBF and the i ncreasement of cytokines developed simultaneously in rats with AP, hence both of them are important pathogenic factors of AP.