Predictive value of early lactate/albumin ratio in the prognosis of sepsis / 中华危重病急救医学

Objective:To investigate the prognostic value of early serum lactate, albumin, and lactate/albumin ratio (L/A) on the 28-day prognosis of adult patients with sepsis.Methods:A retrospective cohort study was conducted among adult patients with sepsis admitted to the First Affiliated Hospital of Xinjiang Medical University from January to December in 2020. Gender, age, comorbidities, lactate within 24 hours of admission, albumin, L/A, interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and 28-day prognosis were recorded. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of lactate, albumin and L/A for 28-day mortality in patients with sepsis. Subgroup analysis of patients was performed according to the best cut-off value, Kaplan-Meier survival curves were drawn, and the 28-day cumulative survival of patients with sepsis was analyzed.Results:A total of 274 patients with sepsis were included, and 122 patients died at 28 days, with a 28-day mortality of 44.53%. Compared with the survival group, the age, the proportion of pulmonary infection, the proportion of shock, lactate, L/A and IL-6 in the death group were significantly increased, and albumin was significantly decreased [age (years): 65 (51, 79) vs. 57 (48, 73), pulmonary infection: 75.4% vs. 53.3%, shock: 37.7% vs. 15.1%, lactate (mmol/L): 4.76 (2.95, 9.23) vs. 2.21 (1.44, 3.19), L/A: 0.18 (0.10, 0.35) vs. 0.08 (0.05, 0.11), IL-6 (ng/L): 337.00 (97.73, 2 318.50) vs. 55.88 (25.26, 150.65), albumin (g/L): 27.68 (21.02, 33.03) vs. 29.62 (25.25, 34.23), all P < 0.05]. The area under the ROC curve (AUC) and 95% confidence interval (95% CI) of lactate, albumin, and L/A were 0.794 (95% CI was 0.741-0.840), 0.589 (95% CI was 0.528-0.647), 0.807 (95% CI was 0.755-0.852) for predicting 28-day mortality in sepsis patients. The optimal diagnostic cut-off value of lactate was 4.07 mmol/L, the sensitivity was 57.38%, the specificity was 92.76%. The optimal diagnostic cut-off value of albumin was 22.28 g/L, the sensitivity was 31.15%, the specificity was 92.76%. The optimal diagnostic cut-off of L/A was 0.16, the sensitivity was 54.92%, and the specificity was 95.39%. Subgroup analysis showed that the 28-day mortality of sepsis patients in the L/A > 0.16 group was significantly higher than that in the L/A ≤ 0.16 group [90.5% (67/74) vs. 27.5% (55/200), P < 0.001]. The 28-day mortality of sepsis patients in the albumin ≤ 22.28 g/L group was significantly higher than that in the albumin > 22.28 g/L group [77.6% (38/49) vs. 37.3% (84/225), P < 0.001]. The 28-day mortality in the group with lactate > 4.07 mmol/L was significantly higher than that in the group with lactate ≤ 4.07 mmol/L [86.4% (70/81) vs. 26.9% (52/193), P < 0.001]. The three were consistent with the analysis results of Kaplan-Meier survival curve. Conclusion:The early serum lactate, albumin, and L/A were all valuable in predicting the 28-day prognosis of patients with sepsis, and L/A was better than lactate and albumin.

Prevalence of uremic pruritus and related factors in patients undergoing hemodialysis / 中国基层医药

Objective:To investigate the prevalence of uremic pruritus and related factors in patients undergoing hemodialysis.Methods:A total of 212 patients with uremia who undergo hemodialysis in the First Affiliated Hospital of Xiamen University in March 2021 were included in this cross-sectional study. Data including gender, age and blood biochemical indicators were collected. The 5D itch scale was used to evaluate skin itch in patients. The included patients were divided into pruritus and no pruritus groups according to evaluation results. Related indicators were compared between the two groups. Binary logistic regression analysis of skin itch related factors was performed.Results:According to 5D itch scale evaluation results, 129 patients (60.85%) of the 212 patients had no skin pruritus, and 83 patients (39.15%) had skin pruritus. In the pruritus group, age, hypersensitive C-reactive protein, alkaline phosphatase, brain natriuretic peptide, ferritin were 63.0 (51.0, 72.0) years, 1.66 (0.30, 7.85) mg/L, 93.0 (70.0, 118.0) U/L, 192.0 (84.9, 446.4) ng/L and 421.0 (291.6, 577.6) μg/L, respectively, which were significantly higher than 53.0 (42.0, 63.0) years, 0.40 (0.30, 1.88) mg/L, 79.0 (62.0, 99.0) U/L, 143.3 (65.8, 256.5) ng/L, 356.8 (203.3, 528.4) μg/L in the pruritus group ( Z = -3.14, -3.96, -3.05, -2.88, -2.11, all P < 0.05). Increased hypersensitive C-reactive protein, brain natriuretic peptide, ferritin levels ( Wald = 14.58, 4.17, 4.23, all P < 0.05) were independent risk factors for uremic pruritus. Conclusion:Uremic pruritus remains a serious problem in patients undergoing hemodialysis. Increased hypersensitive C-reactive protein, ferritin, brain natriuretic peptide levels are independent risk factors for uremic pruritus. In clinical work, physicians should focus on strengthening the early identification of patients, optimizing treatment measures, and improving the quality of life of patients.

TNFα Induces Multidrug Resistance-Associated Protein 4 Expression through p38-E2F1-Nrf2 Signaling in Obstructive Cholestasis

PURPOSE: To explore the molecular mechanism of the upregulation of multidrug resistance-associated protein 4 (MRP4) in cholestasis. MATERIALS AND METHODS: The mRNA and protein levels of MRP4 in liver samples from cholestatic patients were determined by quantitative real-time PCR and Western blot. In human hepatoma HepG2 cells, electrophoretic mobility shift assay (EMSA) was used to determine the affinity of nuclear factor-E2-related factor (Nrf2) binding to MRP4 promoter. Dual-luciferase reporter assay was used to detect the binding of tumor necrosis factor α (TNFα) to the promotor of E2F1. The bile duct ligation mouse models were established using male C57BL/6 mice. RESULTS: The mRNA and protein levels of MRP4 were significantly increased in cholestatic patients. TNFα treatment induced the expression of MRP4 and Nrf2 and enhanced cell nuclear extract binding activity to MRP4 promoter, as demonstrated by EMSA. Nrf2 knockdown reduced MRP4 mRNA levels in both HepG2 and Hep-3B cells. In addition, TNFα increased Rb phosphorylation and expression of MRP4 and Nrf2 and activated E2F1 and phosphorylated p38 in HepG2 and Hep-3B cells. These effects were markedly inhibited by pretreatment with E2F1 siRNA. Dual-luciferase reporter assay validated that TNFα induces the transcription of E2F1. Furthermore, the expression of MRP4, Nrf2, E2F1, and p-p38 proteins was improved with treatment of TNFα in a mouse model of cholestasis. E2F1 siRNA lentivirus or SB 203580 (p38 inhibitor) inhibited these positive effects. CONCLUSION: Our findings indicated that TNFα induces hepatic MRP4 expression through activation of the p38-E2F1-Nrf2 signaling pathway in human obstructive cholestasis.

Efficacy and mechanism of compound glycyrrhizin on serious hepatitis: report of 30 patients / 第三军医大学学报

Objective To investigate the efficacy and mechanism of compound glycyrrhizin on patients with serious hepatitis. Methods Thirty patients who were hospitalized from August 2005 to June 2007 with diagnosed with serious hepatitis were enrolled into treatment group and treated by compound glycyrrhizin injection ( 80 to 100 ml per day,for 3 consecutive weeks) and common supporting medicines,while the other 30 patients in control group were treated only with same supporting medicines. Mortality,biochemical parameters, plasma levels of endotoxin and inflammatory factors in patients of both groups were observed during the treatment. Results By the end of three-week of treatment,8 patients in the treatment group died with the mortality of 26. 7% ( 8 /30) . Thirteen patients died in the control group and the mortality was 43. 3% ( 13 /30) . Serum ALT and AST levels in treatment group were significantly lower than those of control group during the treatment. The average level of serum total bilirubin and plasma prothrombin time in treatment group was lower than those of control group by end of the third treatment week. The level of TNF-alpha in treatment group was lower than that of control group during treatment. The levels of plasma endotoxin and interleukin-6 in treatment group were significantly lower than those of the control group at the second and third treatment week. Conclusion Compound glycyrrhizin improves the biochemical parameters of patients with serious hepatitis,and probably,improves the survival of patients with severe hepatitis. The implying mechanism might be that compound glycyrrhizin declines plasma endotoxin levels and lessen cytokine-induced secondary hepatic injuries.