Jinxiu Li

The Cold-Inducible RNA-Binding Protein (CIRP) Level in Peripheral Blood Predicts Sepsis Outcome

Objectives Sepsis is a lethal and complex clinical syndrome caused by infection or suspected infection. Cold-inducible RNA-binding protein (CIRP) is a widely distributed cold-shock protein that plays a proinflammatory role in sepsis and that may induce organ damage. However, clinical studies regarding the use of CIRP for the prognostic evaluation of sepsis are lacking. The purpose of this research was to investigate the prognostic significance of peripheral blood concentrations of CIRP in sepsis. Sepsis was assessed using several common measures, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score; the Sepsis-related Organ Failure Assessment (SOFA) score; the lactate, serum creatinine, and procalcitonin (PCT) levels; the white blood cell (WBC) count; and the neutrophil ratio (N%). Design Sixty-nine adult patients with sepsis were enrolled in this study. According to the mortality data from the hospital, 38 patients were survivors, and 31 were nonsurvivors. The plasma levels of the biomarkers were measured and the APACHE II and SOFA scores were calculated within 24 hours of patient enrollment into our study. The CIRP level was measured via ELISA. Results The plasma level of CIRP was significantly higher in the nonsurvivors than in the survivors (median (IQR) 4.99 (2.37–30.17) ng/mL and 1.68 (1.41–13.90) ng/mL, respectively; p = 0.013). The correlations of the CIRP level with the APACHE II score (r = 0.248, p = 0.040, n = 69), the SOFA score (r = 0.323, p = 0.007, n = 69), the serum creatinine level (r = 0.316, p = 0.008, n = 69), and the PCT level (r = 0.282, p = 0.019, n = 69) were significant. Receiver operator characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) for the CIRP level was 0.674 (p = 0.013). According to Cox proportional hazards models, the CIRP level independently predicts sepsis mortality. When the CIRP level in the peripheral blood increased by 10 ng/mL, the mortality risk increased by 1.05-fold (p = 0.012). Thus, the CIRP level reflects the degree of renal injury but does not predict the severity of sepsis or organ damage. Conclusion An elevated plasma concentration of CIRP was significantly associated with poor prognosis among patients with sepsis. Therefore, CIRP is a potential predictor of sepsis prognosis.

Aloperine protects mice against ischemia reperfusion (IR)-induced renal injury by regulating PI3K/AKT/mTOR signaling and AP-1 activity.

Aloperine is a quinolizidine alkaloid extracted from the leaves of Sophora plants. It has been recognized with the potential to treat inflammatory and allergic diseases as well as tumors. In this report, we demonstrate that pretreatment with aloperine provided protection for mice against ischemia-reperfusion (IR)-induced acute renal injury as manifested by the attenuated inflammatory infiltration, reduced tubular apoptosis, and well-preserved renal function. Mechanistic studies revealed that aloperine selectively repressed IL-1β and IFN-γ expression by regulating PI3K/Akt/mTOR signaling and NF-κB transcriptional activity. However, aloperine did not show a perceptible impact on IL-6 and TGF-β expression and the related Jak2/Stat3 signaling. It was also noted that aloperine regulates AP-1 activity, through which it not only enhances SOD expression to increase reactive oxygen species (ROS) detoxification but also promotes the expression of antiapoptotic Bcl-2, thereby preventing tubular cells from IR-induced apoptosis. Collectively, our data suggest that administration of aloperine prior to IR insults, such as renal transplantation, could be a viable approach to prevent IR-induced injuries.

Blockade of dopamine D1-like receptor signalling protects mice against OVA-induced acute asthma by inhibiting B-cell activating transcription factor signalling and Th17 function

Previous studies have consistently demonstrated that dopamine D1‐like receptor (D1‐like‐R) signalling is implicated in the pathogenesis of experimental autoimmune encephalomyelitis and type I diabetes. Given that allergic asthma shares certain disease aetiology similarities with autoimmune diseases, we conducted studies in OVA‐induced mice aiming to address the impact of D1‐like‐R signalling on the pathogenesis of allergic asthma. It was noted that blockade of D1‐like‐R signalling provided protection for mice against OVA‐induced acute asthma. Particularly, treatment of OVA‐induced mice with SCH23390, a D1‐like‐R antagonist, significantly attenuated inflammatory infiltration in the airways along with repressed goblet cell hyperplasia and mucus production, as well as airway resistance. By contrast, administration of SKF83959, a D1‐like‐R agonist, displayed the opposite effect. Blockade of D1‐like‐R signalling impaired Th17 function, as manifested by a significant reduction of Th17 cells in the spleen and bronchoalveolar lavage fluid. Mechanistic studies revealed that D1‐like‐R signalling enhances B‐cell activating transcription factor activity, which then transcribes the expression of RORγt, a Th17 transcription factor; accordingly, D1‐like‐R signalling regulates Th17 differentiation to promote the development of allergic asthma. Taken together, the data obtained in the present suggest that blockade of D1‐like‐R signalling could be an effective therapeutic strategy for the prevention and treatment of allergic asthma in clinical practice.

Comparative analysis of the alveolar macrophage proteome in ALI/ARDS patients between the exudative phase and recovery phase

BackgroundDespite decades of extensive studies, the morbidity and mortality for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remained high. Particularly, biomarkers essential for its early diagnosis and prognosis are lacking.MethodsRecent studies suggest that alveolar macrophages (AMs) at the exudative phase of ALI/ARDS initiate, amplify and perpetuate inflammatory responses, while they resolve inflammation in the recovery phase to prevent further tissue injury and perpetuated inflammation in the lung. Therefore, proteins relevant to this functional switch could be valuable biomarkers for ALI/ARDS diagnosis and prognosis. We thus conducted comparative analysis of the AM proteome to assess its dynamic proteomic changes during ALI/ARDS progression and recovery.Results135 proteins were characterized to be differentially expressed between AMs at the exudative and recovery phase. MALDI-TOF-MS and peptide mass fingerprint (PMF) analysis characterized 27 informative proteins, in which 17 proteins were found with a marked increase at the recovery phase, while the rest of 10 proteins were manifested by the significantly higher levels of expression at the exudative phase.ConclusionsGiven the role of above identified proteins played in the regulation of inflammatory responses, cell skeleton organization, oxidative stress, apoptosis and metabolism, they have the potential to serve as biomarkers for early diagnosis and prognosis in the setting of patients with ALI/ARDS.

Effects and mechanism of dehydroepiandrosterone on epithelial–mesenchymal transition in bronchial epithelial cells

ABSTRACT Background: Chronic persistent asthma is characterized by airway remodeling, in which epithelial–mesenchymal transition (EMT) may play a significant role. Dehydroepiandrosterone (DHEA), a steroid hormone and testosterone analog, is considered as an important immunomodulating hormone. However, its role in EMT remains unclear. We sought to investigate whether transforming growth factor-β1 (TGF-β1) stimulates human bronchial epithelial cells (16HBE-14o) to undergo EMT, and whether this transition can be abrogated by DHEA. Methods: The 16HBE-14o cells were stimulated with 5 ng/ml TGF-β1 for 3 days to induce EMT, with or without DHEA pretreatment, and assayed for epithelial or mesenchymal markers using Western Blot. The involvement of phosphoinositide 3-kinase (PI3K) -mediated signaling pathway was also evaluated, the epithelial cells were also incubated with pharmacological approaches (agonists and antagonists of Akt, LY294002 or IGF-1) or flutamide, the antagonist of androgen receptor. Results were analyzed using nonparametric statistical tests. Results: Our data demonstrate that treatment of 16HBE-14o cells with TGF-β1 for 3 days induced EMT as reflected by conversion to the spindle-like morphology, loss of E-cadherin, and acquisition of a-smooth muscle actin (a-SMA). Pretreatment of 16HBE-14o cells with DHEA preserved the epithelial-like morphology, restored the expression of E-cadherin, and abolished the activation of a-SMA, and this effect is a PI3K-dependent mechanism. Conclusion: Our results indicate that TGF-β1 induces EMT in a PI3K-dependent manner in 16HBE-14o cells. DHEA inhibits the bronchial epithelial to mesenchymal transition via the inhibition of PI3K/Akt-dependent signal pathway stimulated by TGF-β1. Therefore, DHEA may be a useful therapy for asthma.

Change of serum soluble CD14 level in newly diagnosed type 2 diabetes and its significance

OBJECTIVE To determine the correlation of serum soluble CD14 (sCD14) level with the injury of vascular endothelial cells and chronic low grade inflammation in newly diagnosed Type 2 diabetes (T2DM). METHODS ELISA was used to examine serum sCD14 and serum soluble E-selectin (sE-selectin) level, while immunoturbidimetric assay was used to detect serum high sensitivity C reactive protein (hsCRP). RESULTS The levels of serum sCD14, sE-selectin, and hsCRP in newly diagnosed T2DM group were higher than those in the euglycemic group [sCD14: (300.7+/-136.6) ng/mL vs. (273.3+/-86.0) ng/mL); sE-selectin: (21.3+/-7.7) ng/mL vs. (32.9+/-11.4) ng/mL; hsCRP: (1.45+/-1.21) mg/L vs. (2.37+/-1.45)mg/L], and there was a significant difference in the latter two parameters between the 2 groups(P<0.01). In the patients with newly diagnosed T2DM, after matching blood pressure, blood sugar, and blood lipid, the levels of serum sCD14, sE-selectin, and hsCRP in the obese group were higher than those in the non-obese group. There was no significant difference in the former 2 parameters between the 2 groups. The serum sE-selectin was correlated with fasting blood sugar (r=0.369, P<0.001), 2-hour postprandial blood sugar (r=0.421, P<0.001), glycosylated hemoglobin (r=0.291, P=0.005), sCD14(r=0.312, P=0.002), and homeostasis model assessment-insulin resistance(r=0.247, P=0.018) in the newly diagnosed T2DM group. Stepwise regression ana-lysis showed that the serum sCD14 was one of the chief influencing factors on serum sE-selectin. CONCLUSION Serum sCD14 levels tend to increase in newly diagnosed T2DM patients, especially in the obese diabetic patients, which is one of the chief influencing factors to induce the injury of vascular endothelial cells. The innate immunity mediated by Toll-like receptor 4 may take part in the injury of vascular endothelial cells in newly diagnosed T2DM patients.

Clinical analysis of critically ill patients with H1N1 influenza.

OBJECTIVE To determine the clinical characteristic, main treatment, and prognosis for the sake of more effective treatments for critically ill patients with H1N1 influenza. METHODS Eight critically ill patients with H1N1 influenza in intensive care unit were retrospectively studied, including clinical characteristics, indexex of correlation, and prognosis. RESULTS The acute physiology and chronic health evaluation II score was 19.0+/-7.8. Five patients died, 4 of whom were caused by respiratory failure. The number of platelets in dead patient was lower than that in healing and improved ones(χ²=8.000,P<0.05).All the 4 patients treated with glucocorticoid died, 5 out of the 6 patients received invasive mechanical ventilation rather than noninvasive mechanical ventilation, and 3 of them who complicated barotraumas in the lung died at last. CONCLUSION Critically ill patients with H1N1 influenza have high mortality. Respiratory failure is the main cause of death. Critically ill patients with H1N1 influenza should not be treated with glucocorticoid. Patients who need mechanical ventilation should be treated with invasive mechanical ventilation with low tidal volume and low positive end-expiratory pressure.

Danger of injudicious use of tui-na therapy in ankylosing spondylitis

Tui-na is a very important component of Chinese medicine. It is a well-respected treatment modality known to be helpful and safe for a wide range of conditions. It can be considered as a certain kind of massage which is performed at acupoints, meridians, and collaterals by pushing, finger twisting, grasping thumb waving pressing, patting, palm twisting, and other manipulation techniques. At present, it is extensively used for relieving pain and stiffness associated with ankylosing spondylitis in China, even though there is a lack of evidence to support its validation and feasibility. The patient in this case was treated by tui-na massage at acute flare-up of ankylosing spondylitis and ended up with catastrophic results.

An unusual infection in a patient with peripherally inserted central catheter

A peripherally inserted central catheter (PICC) is widely used in transfusion therapy and for monitoring many kinds of diseases, especially in critically ill patients. Compared with other catheters, it has a lower risk of catheter-related bloodstream infections. Aeromonas Hydrophila (AH) is a kind of opportunistic pathogen, vibrionaceae aeromonas, and gramnegative brevibacterium, widely distributed in nature, in all kinds of body fluid. It usually causes gastrointestinal infections, and rarely causes Aeromonas septicemia. To date, there has been no report of a PICCrelated AH infection. We report the case of a 40-year-old female with breast cancer, who suffered post-op. severe sepsis and double lower limb cellulitis with multiple organ failure. All of this was due to AH invading the blood through the PICC.

Change and significance of peripheral blood Th17 cells in patients with acute asthma

OBJECTIVE To observe the change of peripheral blood Th17 cells and relationship between the severity and Th17 cells in patients with acute asthma. METHODS We recruited patients with mild acute asthma(n=10) and severe acute asthma(n=10), and healthy volunteers(n=10). T-lymphocytes were collected from the peripheral blood mononuclear cells (PBMC). Flow cytometer (FCM) was used to detect the expression of peripheral blood Th17 cells. IL-17 levels in the peripheral blood were measured by enzyme-linked immunosorbentassay (ELISA). RESULTS The rate of positive Th17 cells of peripheral blood in the severe acute asthma group was higher than that in the mild acute asthma group(P<0.05) and the rate of positive Th17 cells of peripheral blood in healthy volunteer group were the lowest among all groups (P<0.05, respectively). The level of IL-17 in the peripheral blood of patients with severe acute asthma increased significantly compared with that in patients with mild acute asthma and healthy volunteers (P<0.05). The positive Th17 cells of peripheral blood in patients with acute asthma were positively correlated with the severity of acute asthma(r=0.869, P<0.05). CONCLUSION The positive rate of Th17 cells in the peripheral blood increases in patients with acute asthma and has positive correlation with the severity of acute asthma.