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Critically ill patients with preexisting kidney dysfunction (PKD) are at high risk for acute kidney injury (AKI). Nevertheless, there is no criteria for screening and classifying AKI in patients with PKD. In this study, after assessing relationship between the change in SCr from baseline and in-hospital mortality, a new criteria, named APKD, for identifying AKI in PKD was proposed. APKD defined AKI in critically ill patients with PKD as an absolute increase of ≥ 0.2 mg/dL in SCr within 48 h or an increase in SCr ≥ 1.1 times over baseline within 7 d. APKD detected more AKI among PKD patients compared with the other criteria. Additionally, the AKI patients identified by APKD but missed by the other criteria had higher mortality than those without AKI. APKD shows higher sensitivities than KDIGO criteria in predicating in-hospital mortality. APKD, but not the KDIGO, is effective for staging the severity of AKI in patients with PKD. In conclusion, APKD is more effective in screening and classifying AKI in critically ill patients with PKD compared with the earlier criteria, and it may helpful in guiding clinical treatment and predicting prognosis. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease, associated with chronic inflammation and the imbalance of Th17/Treg. Stanniocalcin‐1 (STC‐1), a glycoprotein, was found to have anti‐inflammatory, anti‐oxidative stress and anti‐apoptosis properties. The present study aimed to investigate the immunomodulatory effect of STC‐1 and its potential value in the treatment of RA. Here, a mouse model of collagen‐induced arthritis (CIA) was established. Then body weight, joint erythema and swelling were measured in CIA mice with or without STC‐1 treatment. Haematoxylin and eosin (H and E) staining was performed to determine histopathological change. Moreover, the percentage of Th17 and Treg cells in the spleen and inguinal lymph nodes (ILNs) and the culture supernatant in polarizing conditions were examined by flow cytometry. Cytokines in serum were detected by ELISA. As a result, the arthritis score, histologic inflammation and cartilage destruction were decreased in CIA mice treated with STC‐1. STC‐1 increased the level of transforming growth factor‐β and inhibited the expression of interleukin‐17. In CIA mice, the percentage of CD4+IL‐17A+ cells in the spleen and ILNs were decreased after STC‐1 treatment, while the level of CD4+Foxp3+ cells did not change significantly. In vitro, STC‐1 inhibited Th17 cell differentiation and STAT3 phosphorylation in CD4+ T cells under Th17 cell‐polarizing conditions. Collectively, the results demonstrated that STC‐1 alleviated RA by inhibiting Th17 cell differentiation through regulating STAT3 phosphorylation. STC‐1 may be a potential drug for the treatment of RA. [ABSTRACT FROM AUTHOR]

Objective: To explore the value of vascular endothelial-cadherin (VE-cad) in evaluating the severity of sepsis., Methods: A prospective study was conducted to select 85 patients with sepsis treated in the emergency ward of the First Affiliated Hospital of Wenzhou Medical University from June 1, 2015 to November 1, 2017. The gender, age, medical history, first infection site, number of affected organs, laboratory indexes, acute physiology and chronic health evaluation II (APACHE II), simplified acute physiology score II (SAPS II), sequential organ failure assessment (SOFA) and the total length of stay, emergency intensive care unit (EICU) length of stay, 28-day at admission and survival during hospitalization were measured, and the VE-cad level within 24 hours at admission was measured. The patients were divided into sepsis group and septic shock group according to the progress of the disease. The patients were divided into multiple organ dysfunction syndrome (MODS) group and non MODS group according to whether they were accompanied by MODS. The differences of the above indexes in patients with different disease progression, MODS and different prognosis were analyzed and compared. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the value of VE-cad in evaluating the severity of sepsis., Results: A total of 85 patients were included, mainly respiratory tract infection. Among them, 38 cases were sepsis and 47 cases were septic shock, 39 cases had MODS, 46 cases had no MODS, 64 cases survived and 21 cases died within 28 days after admission. Compared with sepsis group, the number of affected organs in septic shock group was greater [3 (2, 4) vs. 1 (0, 2)], APACHE II score [13 (10, 21) vs. 7 (5, 12)], SAPS II score [35 (31, 55) vs. 7 (5, 12)], SOFA score [7.0 (5.0, 10.0) vs. 3.0 (0, 5.0)], blood lactic acid [Lac (mmol/L): 3.5 (2.4, 6.2) vs. 1.9 (1.2, 2.2)], C-reactive protein [CRP (mg/L): 90.0 (58.1, 90.0) vs. 50.5 (38.0,90.0)] and VE-cad levels [mg/L: 1.427 (1.141, 2.150) vs. 1.195 (0.901, 1.688)] were significantly increased, while platelet count [PLT (×10 9 /L): 113.4±67.2 vs. 202.5±109.5] and hemoglobin (Hb) levels (g/L: 106.3±36.3 vs. 118.6±18.0) were significantly decreased (all P < 0.05). Compared with non MODS group, APACHE II score [14 (10, 22) vs. 8 (6, 13)], SAPS II score [36 (32, 56) vs. 29 (24, 35)], SOFA score (7.9±3.9 vs. 4.0±3.8), in-hospital mortality [53.8% (21/39) vs. 0% (0/46)], Lac [mmol/L: 3.1 (2.3, 6.3) vs. 2.1 (1.4, 4.6)] and VE-cad levels [mg/L: 1.427 (1.156, 1.937) vs. 1.195 (0.897, 1.776)] in MODS group were significantly higher, the length of stay in EICU was significantly longer [days: 6 (3, 12) vs. 3 (0, 7)], and the PLT level was significantly lower (×10 9 /L: 118.2±80.0 vs. 182.5±104.0, all P < 0.05). Compared with the death group, the number of affected organs in the survival group was fewer [2 (1, 3) vs. 3 (1, 5)], APACHE II score [9 (6, 13) vs. 21 (13, 25)], SAPS II score [31 (25, 36) vs. 55 (35, 63)] and SOFA score (4.7±3.7 vs. 8.9±4.5) were significantly reduced, and the length of stay in EICU [days: 4 (1, 8) vs. 8 (3, 15)] was significantly shorter (all P < 0.05). ROC curve analysis showed that area under the ROC curve (AUC) of VE-cad, SOFA score and VE-cad combined with SOFA score in evaluating the severity of sepsis were 0.632 [95% confidence interval (95%CI) was 0.513-0.750], 0.830 (95%CI was 0.744-0.916) and 0.856 (95%CI was 0.779-0.933), respectively. When the cut-off value of VE-cad was 1.240 mg/L, the sensitivity was 68.1% and the specificity was 55.3%, the sensitivity of VE-cad combined with SOFA score was 85.1%, the specificity was 73.7%., Conclusions: VE-cad has a certain evaluation value for the severity of sepsis, and the evaluation value of VE-cad combined with SOFA score is better than that of VE-cad single index.

Sirtuin 1 (SIRT1) acts via the deacetylation of a number of crucial transcription factors and has been implicated in various biological processes, including oxidative stress. Previous studies have indicated that nuclear factor, erythroid 2‑like 2 (NRF2) is an effective target of antioxidant therapy for paraquat (PQ) poisoning. However, the association between SIRT1 and NRF2 and their effects in PQ‑induced oxidative stress remains to be elucidated. The current study demonstrated that PQ exposure upregulated the expression of SIRT1 and NRF2 following 6‑ and 24‑h exposure in the lungs of mice. However, long‑term exposure to PQ significantly decreased the expression of SIRT1 and NRF2. Resveratrol is a SIRT1 activator, and strongly enhanced SIRT1 expression and attenuated the lung injury resulting from PQ exposure in the current study. Additionally, treatment with resveratrol upregulated the expression of NRF2 and glutathione, increased the activity of heme oxygenase‑1, superoxide dismutase and catalase, but depleted the expression of malondialdehyde. The present results demonstrated that resveratrol reduced PQ‑induced oxidative stress and lung injury, potentially through the positive feedback signaling loop between SIRT1 and NRF2.

Objective: To investigate the protective effect of paraoxonase 1 (PON1) gene against liver oxidative stress injury in mice due to dichlorvos poisoning., Methods: Experiment 1: 12 male Balb/c mice were randomly divided into three groups, with 4 mice in each group: control group, green fluorescent protein lentivirus control group (Lv-GFP group), and recombinant PON1 lentivirus group (Lv-PON1 group). 2 × 10⁷ TU of Lv-GFP or Lv-PON1 was transfected via tail vein, while normal saline was given to those in control group. Blood was collected on 0, 1, 3, 5, 7, 9 days via fundus venous plexus for the assay of serum PON1 activity. PON1 mRNA and protein expression levels were respectively determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot on the 3rd post-lentivirus transfection day. Experiment 2: according to the random number table method, another 96 male Balb/c mice were divided into four groups of 24 mice in each control group, dichlorvos group, Lv-GFP intervention group, and Lv-PON1 intervention group. Lv-GFP or Lv-PON1 was transfected via tail vein followed by intraperitoneal injection of dichlorvos 9 mg/kg, while those in control group were given normal saline. Six mice in each group were sacrificed respectively at 6, 12, 24, 48 hours, and liver tissue was collected. PON1 mRNA and nuclear factor E2-related factor 2 (Nrf2) mRNA expression levels were determined by RT-PCR, and PON1 protein level was determined by Western Blot. The content of malondialdehyde (MDA) and glutathione (GSH) in the liver tissue were determined by chemical colorimetry. The activity of superoxide dismutase (SOD) and catalase (CAT) were measured by double antibody sandwich enzyme linked immunosorbent assay (ELISA)., Results: Experiment 1: after Lv-PON1 was transfected to normal mice, PON1 activity in serum gradually increased and maintained a high level on 3rd day, while that of the control group and Lv-GFP group showed a normal low level. On the 3rd post-lentivirus transfection day, PON1 mRNA and PON1 protein expressions in liver were significantly higher than those of control group and Lv-GFP group. Experiment 2: compared with control group, the mice in dichlorvos group showed significant decreases in PON1 mRNA, PON1 protein, Nrf2 mRNA as well as GSH, SOD, CAT levels at 6 hours [PON1 mRNA (gray value): 0.237 ± 0.075 vs. 0.674 ± 0.011, PON1 protein (gray value): 0.602 ± 0.086 vs. 0.998 ± 0.124, Nrf2 mRNA (gray value): 0.089 ± 0.012 vs. 0.126 ± 0.010, GSH (mg/g): 3.84 ± 0.33 vs. 5.52 ± 0.40, SOD (μg/g): 0.383 ± 0.040 vs. 0.564 ± 0.052, CAT (ng/g): 7.32 ± 1.28 vs. 12.46 ± 1.54, all P < 0.05 ], and remarkable increase in MDA content (nmol/g: 7.78 ± 0.41 vs. 2.34 ± 0.25, P < 0.05). With the extension of time, PON1 mRNA, PON1 protein, Nrf2 mRNA and GSH, SOD, CAT levels gradually increased, MDA content gradually decreased, Nrf2 mRNA expression level had risen to the level of control group at 24 hours (0.133 ± 0.019 vs. 0.126 ± 0.009, P > 0.05), and it was higher than that of the control group at 48 hours ( 0.206 ± 0.028 vs. 0.124 ± 0.010, P < 0.05). Compared with that of the dichlorvos group, Lv-PON1 intervention group showed a significant increase in PON1 mRNA, PON1 protein, Nrf2 mRNA and GSH, SOD, CAT levels [PON1 mRNA (gray value): 0.726 ± 0.021 vs. 0.237 ± 0.075, PON1 protein (gray value): 0.739 ± 0.050 vs. 0.602 ± 0.086, Nrf2 mRNA (gray value): 0.158 ± 0.007 vs. 0.089 ± 0.012, GSH (mg/g): 4.30 ± 0.22 vs. 3.84 ± 0.33, SOD ( μg/g): 0.454 ± 0.062 vs. 0.383 ± 0.040, CAT (ng/g): 8.98 ± 1.02 vs. 7.32 ± 1.28, all P < 0.05 ], and a decrease in MDA content (nmol/g: 6.56 ± 0.44 vs. 7.78 ± 0.41, P < 0.05)., Conclusions: Regulation of PON1 gene can reduce MDA content, enhance SOD and CAT activities, increase GSH content, and it may also up-regulate Nrf2 mRNA expression to play a protective effect against oxidative stress of liver injury induced by dichlorvos poisoning.