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Objective:To investigate the diagnostic value of mitochondrial associated protein fumarylacetoacetate domain containing protein 1 (FAHD1) and growth differentiation factor-15 (GDF-15) in sepsis.Methods:Based on the database of the whole process of sepsis early warning, diagnosis and treatment management, which was established on the study of sepsis early warning and standardized diagnosis and treatment system, adult patients with suspected infection admitted to the department of critical care medicine of Zhejiang Hospital, Second Affiliated Hospital of Zhejiang University, the First Affiliated Hospital of Sun Yat-Sen University, West China Hospital of Sichuan University, Ningbo First Hospital from May 2014 to October 2015 were enrolled. The basic vital signs, and the main blood routine results, liver and kidney function, blood gas, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) score at the time of diagnosis of patients with or without sepsis were analyzed. The preserved serum samples were taken, the levels of procalcitonin (PCT), C-reactive protein (CRP) were detected by electrochemiluminescence method, immunoturbidimetry respectively, and FAHD1 and GDF-15 were detected by enzyme linked immunosorbent assay (ELISA). Univariate and multivariate Logistic regression were used to analyze the risk factors for sepsis diagnose. The indexes' diagnostic efficacy in sepsis were analyzed by receiver operating characteristics curve (ROC curve).Results:A total of 132 patients were enrolled, including 76 cases of sepsis and 56 cases of non-sepsis. Compared with the non-sepsis group, the heart rate in the sepsis group was increased (bpm: 116.4±17.8 vs. 97.4±19.1), while the mean arterial pressure (MAP), platelet count (PLT), arterial partial pressure of oxygen (PaO 2) were significantly decreased [MAP (mmHg, 1 mmHg = 0.133 kPa): 65.8±9.7 vs. 74.7±10.3, PLT (×10 9/L): 120 (69, 204) vs. 163 (117, 239), PaO 2 (mmHg): 83.0 (66.6, 108.0) vs. 108.0 (84.4, 130.0), all P < 0.05], direct bilirubin (DBil), serum creatinine (SCr), lactic acid (Lac), APACHEⅡ score and SOFA score were significantly increased [DBil (μmol/L): 13.00 (5.55, 55.31) vs. 6.20 (2.20, 21.90), SCr (μmol/L): 118.00 (70.00, 191.73) vs. 77.20 (59.65, 110.86), Lac (mmol/L): 2.90 (1.50, 4.10) vs. 1.90 (1.20, 2.80), APACHEⅡ score: 20.0 (16.0, 25.0) vs. 16.0 (10.0, 21.0), SOFA score: 12.0 (8.0, 16.0) vs. 8.0 (5.0, 13.0), all P < 0.05]. In addition, the serum levels of FAHD1, GDF-15, PCT and CRP in sepsis group were significantly higher than those in non-sepsis group [FAHD1 (μg/L): 3.96 (2.25, 5.92) vs. 2.47 (1.03, 3.54), GDF-15 (μg/L): 8.46 (4.37, 19.68) vs. 4.32 (1.74, 10.39), PCT (μg/L): 3.79 (1.37, 11.32) vs. 0.42 (0.12, 2.14), CRP (mg/L): 154.43 (61.33, 283.20) vs. 65.95 (28.15, 144.69), all P < 0.01]. Multivariate Logistic regression showed that serum FAHD1 [odds ratio ( OR) = 1.135, 95% confidence interval (95% CI) was 1.045-1.234], GDF-15 ( OR = 1.090, 95% CI was 1.029-1.155) and CRP ( OR = 1.007, 95% CI was 1.002-1.011) were risk factors for sepsis (all P < 0.05). ROC curve analysis of sepsis showed that the areas under ROC curve (AUC) of serum mitochondrial associated proteins FAHD1 and GDF-15 were 0.727 (95% CI was 0.641-0.802) and 0.677 (95% CI was 0.588-0.757), respectively; and the AUC of classical infection indexes PCT and CRP were 0.767 (95% CI was 0.683-0.837) and 0.680 (95% CI was 0.59-0.760), respectively. There was no significant difference between the AUC of mitochondrial associated proteins and classical infection indexes. The combination of FAHD1, GDF-15, PCT and CRP had the largest AUC, which was 0.809 (95% CI was 0.730-0.874), and the sensitivity was 75.00%, and the specificity was 80.00%. Conclusion:Mitochondrial associated protein FAHD1 and GDF-15 are associated with sepsis, and the diagnostic efficiency is improved when combined with PCT and CRP, which might provide experimental basis for screening diagnostic markers of sepsis.
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Objective We aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the treatment of ulcerative colitis (UC) in this Meta-analysis.Methods Literature related to FMT for the treatment of UC from PubMed,Embase,Cochrane databases,CNKI,VIP and Wanfang Data were searched and screened with update study in May 2018.Two independent investigators extracted information according to inclusion and exclusion criteria.The Meta-analysis was conducted by Stata 12.0 software.Results A total of 4 randomized controlled trials (RCTs) and 19 non-randomized controlled trials (non-RCTs) including 536 participants met the inclusion criteria.Meta-analysis of RCTs showed that FMT significantly increased the clinical remission rate (OR=2.47,95％CI 1.40-4.33,P=0.02) and clinical response rate (OR=1.86,95％CI 1.15-3.02,P=-0.01) in UC patients without increasing the incidence of severe adverse effects (OR=1.40,95％CI 0.51-3.79,P=-0.51).The results from 19 non-RCTs showed that clinical remission rate in UC patients with FMT treatment was 20％(95％CI 13％-28％) and the clinical response rate was 50％(95％CI 36％-65％).All adverse events were graded as mild and self-resolving.No FMT-related severe adverse effects were reported.Conclusions Our analysis suggests that FMT is a safe and effective method for the treatment of UC.Considering several limitations of this Meta-analysis and previous clinical trials,further large-scale multicenter RCTs are still required to further verify the conclusion.
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Objective To investigate the role of interleukin-1 receptor type 1 (IL-1R1) signaling in H1N1 influenza virus infection. Methods IL-1R1 knockout ( IL-1R1-/-) mice and wild type ( WT) mice were infected intranasally with 2×104 TCID50(50% tissue culture infective dose) of influenza virus H1N1 PR8. Changes in clinical signs, survivals and bodyweights of those mice were monitored daily for 14 consecutive days. Three mice from each group were sacrificed at 3, 7 and 14 days post infection (d. p. i), from which whole lungs were harvested. A part of the lobes was fixed in 4% paraformaldehyde for histopatho-logical assessment and the rest were split and stored at-80 centigrade for further analysis. Real-time quanti-tative PCR and cytometric bead array ( CBA) were performed to detect viral loads in lungs and inflammatory cytokines in supernatants of lung homogenates. Results The mice in both groups showed severe symptoms after the infection of PR8. The maximum bodyweight loss of IL-1R1-/- mice [(24. 22±0. 80) % at 8 d. p. i] was lower than that of WT mice [(28. 03±1. 51)% at 9 d. p. i] (P<0. 05). The IL-1R1-/- mice with PR8 infection showed a higher survival rate (90%) as compared with that of the control group (40%) (P<0. 05). No statistical differences in virus loads were observed between the two groups at 3, 7 and 14 d. p. i. The lung weight to body weight ratio of IL-1R1-/-mice [(1. 42±0. 03) %] was lower than that of WT mice [(1. 79±0. 08) %] at 3 d. p. i (P<0. 05). Pathological changes in IL-1R1-/- mice were less severe than those in WT mice. CBA detection assay revealed that the proinflammatory cytokines in lungs of IL-1R1-/-mice were less than those in WT mice. Conclusion IL-1R1 signaling plays a pathogenic role in mice infec-ted with 2×104 TCID50 of influenza virus PR8 by promoting inflammatory responses.
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Objective To analyze the Alb-cre/DTR mouse phenotype, and establish a model of induced liver damage to serve basic researches of liver diseases.Methods The introduced Alb-cre and DTR mice were crossed to obtain Alb-cre/DTR mice and the genomic DNAs were extracted from the tail tissue of the mice for genotying by PCR.Diphtheria toxin was intraperitoneally(i.p.)injected into the Alb-cre/DTR mice, then the body weights were monitored and the sera were collected for the detection of serum ALT and AST levels.Results By crossing Alb-cre and DTR mice we obtained the Alb-cre and DTR double transgenic mouse.The intraperitoneal injection of diphtheria toxin in a dose of 0.625 ng/g body weight significantly induced liver injury in these mice, as showed by the elevated levels of ALT and AST, the gross appearance of liver damage and the pathological changes such as necrosis in the liver tissue.Conclusions We have ob-tained a novel mouse strain of Alb-cre/DTR by crossing Alb-cre and DTR mice.Liver damages in those Alb-cre/DTR mice can be induced by injection of diphtheria toxin.This established mouse model of inducible liver damage is a useful platform for the studies of liver damage and recovery, as well as liver transplantation.