Introduction: To investigate the significance of changes in regulatory T cells (Tregs) activity and its relationship with sepsis, as well as outcome of patients with major burns. Methods: The periphery blood samples of 106 patients were collected on post-burn days 1, 3, 7, 14, and 21. Tregs were isolated and their phenotypes (cytotoxic T-lymphocyte-associated antigen 4 and forkhead/winged helix transcription factor p3) were analyzed by flow cytometry, and the contents of cytokines (interleukin-10 and transforming growth factor-β1) released into supernatants by Tregs were also determined by enzyme-linked immunosorbent assay kits. Gene expressions of cytokines were assessed by real-time quantitative polymerase chain reaction. Results: Expressions of Tregs phenotypes and gene/protein expression of cytokines were all elevated after burn, and there were obvious differences among patients with various burn sizes. They were also higher in septic patients than those without sepsis. Among septic patients, the expressions of Tregs phenotypes and the levels of cytokines were markedly lower in the survival group than those in patients with fatal outcome. Conclusions: Severe burn injury per se could lead to the changes in Tregs activities. Elevated levels of cytokines produced by Tregs and activation markers on Tregs surface might play an important role in the pathogenesis of sepsis and mortality in burned patients.

Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7), inducers of G1 cell cycle arrest, are two recently discovered good biomarkers for early diagnosis of acute kidney injury (AKI). To obtain a more robust performance measurement, the present meta-analysis was performed, pooling existing studies. Literature in the MEDLINE (via PubMed), Ovid, Embase, and Cochrane Library databases was systematically searched from inception to 12 October 2016. Studies that met the set inclusion and exclusion criteria were identified by two independent investigators. The diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was evaluated by pooled sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve analyses. The causes of heterogeneity were explored by sensitivity and subgroup analyses. A total of nine published and eligible studies assessing 1886 cases were included in this meta-analysis. Early diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was assessed using a random-effects model. Pooled sensitivity and specificity with corresponding 95% CIs were 0.83 (95% CI 0.79–0.87, heterogeneity I 2 = 68.8%) and 0.55 (95% CI 0.52–0.57, I 2 = 92.9%), respectively. Pooled positive LR, negative LR, and DOR were 2.37 (95% CI 1.87–2.99, I 2 = 82.6%), 0.30 (95% CI 0.21–0.41, I 2 = 43.4%), and 9.92 (95% CI 6.09–16.18, I 2 = 38.5%), respectively. The AUC estimated by SROC was 0.846 (SE 0.027) with a Q* value of 0.777 (SE 0.026). Sensitivity analysis indicated that one study significantly affected the stability of pooled results. Subgroup analysis showed that population setting and AKI threshold were the key factors causing heterogeneity in pooled sensitivity and specificity. On the basis of recent evidence, urinary [TIMP-2] × [IGFBP7] is an effective predictive factor of AKI. PROSPERO registration number: CRD42016051186 . Registered on 10 November 2016.

Context: High-mobility group box 1 (HMGB1) protein is a highly abundant protein that can promote the pathogenesis of inflammatory. Some experiments have demonstrated a vital role for HMGB1 to modulate the immune function of regulatory T-cells (Tregs). Astragaloside IV (AST IV), an extract from Astragalus membranaceus Moench (Leguminosae), has been shown to exert potent cardioprotective and anti-inflammatory effects. It is still unclear whether AST IV has a latent effect on the proinflammatory ability of HMGB1 with subsequent activation of Tregs in vivo. Objective: This research explores the antagonism of different doses of AST IV on the immunologic function of Tregs mediated by HMGB1. Materials and methods: Mouse models (BALB/c) were constructed by which normal saline or AST IV was administered i.p. at 2, 4 and 6 days after the administration i.p. of 20 μg recombinate HMGB1. Spleen was used to procure Treg and CD4 ⁺ CD25⁻ T-cells which were co-cultured with Treg. Cell phenotypes of Tregs(Foxp3) were examined, and the cytokine levels in supernatants and the proliferation of T-cells were assayed. Gene expression was measured by RT-PCR. Results: (1) The expression levels of Foxp3 in Treg on post-stimulus days (PSD) 1–7 were significantly decreased in the HMGB1 group in comparison to those in the control group mice (p < 0.01). The Foxp3 expression was markedly increased in a dose-dependent manner in the AST group as compared with those in the HMGB1 group (p < 0.0 1–0.05). The same results were found in the contents of cytokines (IL-10 and TGF-β) released into supernatants by Treg. (2) When CD4 ⁺ CD25⁻ T-cells were co-cultured with Treg stimulated by HMGB1, the cell proliferation and the levels of cytokines (IL-2 and IFN-γ) in supernatant were markedly increased as compared with those in the HMGB1 group. The level of IL-4 was markedly decreased as compared with that in the HMGB1 group. The same results were found when CD4 ⁺ CD25⁻ T-cells were co-cultured with Treg in the NS group. Compared with those in the NS group, the contrary results were shown in a dose-dependent manner in the AST group. Discussion and conclusion: These results showed that AST IV has a therapeutic effect on inflammation promoted by HMGB1, and it should be studied as a new drug for the treatment of sepsis.

Background: Early allograft dysfunction (EAD) is a common postliver transplant complication that has been associated with graft failure and risk for poor prognosis. There are many risk factors for the incidence of EAD after liver transplantation (LT). This study investigated whether elevated postoperative myoglobin (Mb) increases the incidence of EAD in liver transplanted recipients.Methods: A total of 150 adult recipients who measured Mb within 3 days after liver transplantation between June 2019 and June 2021 were evaluated. Then, all patients were divided into two groups: the EAD group and the non-EAD group. Univariate and multivariate logistic regression analyses were performed, and receiver operating characteristic curves (ROCs) were constructed.Results: The incidence of EAD was 53 out of 150 patients (35.3%) in our study. Based on the multivariate logistic analysis, the risk of EAD increased with elevated postoperative Mb (OR = 1.001, 95% CI 1.000–1.001, P = 0.002). The Mb AUC was 0.657, and it was 0.695 when combined with PCT. When the subgroup analysis was conducted, the AUC of serum Mb prediction was better in patients whose preoperative model for end-stage liver disease score ≤ 15 or operative time ≥ 10 h (AUC = 0.751, 0.758, respectively, or 0.760, 0.800 when combined with PCT).Conclusion: Elevated Mb significantly increased the risk of postoperative EAD, suggesting that postoperative Mb may be a novel predictor of EAD after liver transplantation.The study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100044257, URL: http://www.chictr.org.cn).

Background: Acute kidney injury (AKI) is a common and multifactorial complication after liver transplantation (LT). Myoglobin (Mb) which can be served as O₂ storage and delivery depot is present in muscles and cardiac myocytes. Previous studies had shown the close relationship between Mb and AKI. But there is a lack of clinical studies for Mb with the risk of AKI due to LT. This study was performed to determine the association between the serum level of Mb and incidence of AKI in patients underwent LT. Methods: The clinical data of 140 consecutive adult patients who underwent LT at our center from June 2018 to August 2020 were analyzed in this study. One hundred and fifteen patients met the inclusion criteria. The performances of postoperative laboratory variables (including serum Mb) were evaluated. The outcomes after LT, including the duration of intensive care unit (ICU) stay, hospital stay and 28-day mortality, were also measured. Results: We divided 115 patients into AKI group (n=44) and non-AKI group (n=71). Serum Mb on post-operative day 0 (POD0) was significantly higher in AKI group than those in non-AKI group (P<0.001). According to univariate and multivariable logistic regression analysis, the levels of serum albumin (P=0.024), alanine transaminase (P=0.007) and Mb (P=0.006) on POD0 were independently associated with development of new AKI. The area under curve (AUC) of serum Mb after LT immediately had the best value for predicting AKI [AUC: 0.755, sensitivity: 63.6%, specificity: 77.3%, 95% confidence interval (CI): 0.661–0.849], its cut-off value was 957 ng/mL. Conclusions: Postoperative serum Mb was an independent risk factor for new AKI and could increase the accuracy of predicting the occurrence of post-LT AKI. Trial Registration: The study was registered in Chinese Clinical Trial Registry (registration number: ChiCTR2100044257).