Objective To investigate the occurrence of hepatocyte autophagy and the expression of autophagy associated proteins at different time points in sepsis mice model established by cecal ligation and puncture.Methods Fifty male ICR mice aged 6-8 weeks were randomly (random number) divided into 5 groups:CLP 3 h group,CLP 6 h group,CLP 12 h group,CLP 24 h group and control group.The samples were collected at the corresponding time points after operation.Liver function was tested to obtain alanine aminotransferase (ALT) and aspartate aminotransferase (AST).The expression of TNF-α and IL-6 was detected by ELISA,the inflammation of liver tissue by HE staining while the ultrastructure of autophagosome and autolysosome in liver tissue was observed by electron microscopy.Meanwhile,the expression of LC3 and P62 was detected by Western blot.and the location and quantity of autophagosome was observed by Immunofluorescence.SPSS 21.0 was used for statistical analysis.Two independent sample t tests were performed to compare the two groups,and one-way ANOVA was used for comparison between multiple groups.Results ALT and AST increased significantly after CLP,and peaked at 12 h,respectively (137.8 ±11.94) U/L and (475.3 ±57.34) U/L.The expression of IL-6 peaked at 6 h (2589.63 ±27.96) pg/mL,and TNF-α peaked at 3 h (320.21±8.9) pg/mL.HE staining showed activation of Kupffer cells and infiltration of single granulocyte.Electron microscope showed the formation of autophagosome and autolysosome.Compared with the control group,the ratio of LC3 Ⅱ/Ⅰ increased first and then decreased,peaked at 6 h (t=13.35,P＜0.05).The content of P62 protein declined first and then went up,reaching the lowest level at 6 h (t=66.1 l,P＜0.05),contrary to the trend of LC3 Ⅱ/Ⅰ.Immunofluorescence results illustrated that the fluorescence intensity of LC3 reached its high point at 6 h (t=12.52,P＜0.05).Conclusions Autophagy occurred in the liver of sepsis mice model established by cecal ligation and puncture.The formation of autophagosome first increased and then decreased,reaching its peak at 6 h.

Gut microbiota is composed of trillions of microorganisms inhabiting in the human gastrointestinal tract,profoundly influences many aspects of host physiology.The roles of gut microbiota have been investigated extensively in the gastrointestinal,endocrine,neurological,cardiovascular and immune systems.This article reviews the recent research progress on the function of microbes in healthy organisms,the common research methods for microbiota,and the roles of microbiota in rheumatic immune diseases.It is expected that gut microbiota would be a novel target of clinical diagnosis and treatment for rheumatic immune diseases.

Objective:To compare the early and late predictive value of several critical illness scores (CISs) and biomarkers in patients with bloodstream infection (BSI)-associated pneumonia, and to identify the value of procalcitonin (PCT) in etiological diagnosis.Methods:Patients with at least one positive blood culture within 24 hours admission to department of emergency of China-Japan Friendship Hospital from January 2014 to December 2018 and with final diagnosis of pneumonia were enrolled. Sequential organ failure assessment (SOFA), mortality in emergency department sepsis (MEDS), Logistic organ dysfunction system (LODS), and acute physiology and chronic health evaluationⅡ (APACHEⅡ) scores were calculated based on the first parameters on the day of admission. Differences of various indicators among different Gram-stained bacterial infections and among patients with different prognosis at 28-day or 60-day were compared. Receiver operating characteristic (ROC) curve was used to analyze the value of biomarkers in differential diagnosis of pneumonia caused by single bacterial infection, and the predictive value of several CISs and biomarkers on 28-day and 60-day death of patients with pneumonia.Results:Among 540 patients with pneumonia caused by single bacterial infection, 256 (47.4%) patients with Gram-positive bacteria (GPB) infection and 284 (52.6%) with Gram-negative bacteria (GNB) infection. The 28-day mortality was 29.4% (159/540) and the 60-day mortality was 36.3% (196/540). PCT level was significantly higher in patients with GNB infection than that in GPB infected patients [μg/L: 1.99 (0.32, 13.19) vs. 0.45 (0.13, 3.53), P < 0.01]. There were significant differences of CISs and biomarkers between death group and survival group in predicting 28-day and 60-day mortality in BSI-associated pneumonia. ROC curve analysis showed that: ① the optimal cut-off value of PCT in the diagnosis of single bacterial infection was 0.48 μg/L, with the area under ROC curve (AUC) was 0.739 [95% confidence interval (95% CI) was 0.686-0.793]. When PCT value was greater than 4.49 μg/L, the specificity of diagnostic of GNB infection could reach 81.8%, and the positive predictive value (PPV) was 75.0%. When PCT value was greater than 10.16 μg/L, the diagnostic specificity could reach 91.2%. ② In the prediction of 28-day and 60-day mortality, the SOFA score showed highest AUC [28-day: 0.818 (95% CI was 0.768-0.867), 60-day: 0.800 (95% CI was 0.751-0.849)]. SOFA score greater than 8.5 points could help to predict 28-day and 60-day mortality for pneumonia patients with specificity of 90.5% and 91.6%, respectively. AUC of PCT for predicting 28-day and 60-day mortality in patients with BSI associated with pneumonia was 0.637 (95% CI was 0.575-0.700) and 0.628 (95% CI was 0.569-0.688), respectively. When PCT value was greater than 8.15 μg/L, the specificity and negative predictive value (NPV) were 80.2% and 75.1% respectively, and they could reach 80.2% and 68.7% when PCT value was greater than 7.46 μg/L. Conclusion:PCT is more reliable in the identification of pathogen type in BSI-associated pneumonia, while CISs may be more advantageous in the assessment of early and late prognosis.

Objective:To investigate the protective effect and mechanism of hydroxysafflor yellow A (HSYA) on severe acute pancreatitis (SAP) related lung injury.Methods:Fifty mice were randomly (random number) divided into five groups: the sham-operated group, SAP group and different doses (20, 40 and 80 mg/kg) of HSYA pretreatment group. Mice were pretreated with HSYA 24 h before SAP induction, pancreatic and lung tissues were isolated for histopathological examination at 72 h after modeling, and bronchoalveolar lavage fluid (BALF) was collected for biochemical analysis. Results:Compared with the sham-operated group, serum amylase activity, lung injury pathological score and BALF protein concentration in the SAP group were significantly increased [(2120.44 ± 354.50) U/L vs. (226.72 ± 20.84) U/L; (6.91 ± 0.28) vs. (0.53±0.18); (2563.25±348.22) μg/mL vs. (345.62±56.35) μg/mL, all P<0.05]. Inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels and myeloperoxidase (MPO) activity were increased [(120.5±14.25) pg/mL vs. (31.5±4.82) pg/mL; (214.72±10.62) pg/mL vs. (39.26±5.66) pg/mL; (4.52±0.34) U/mg vs. (1.03±0.17) U/mg]. Compared with the SAP group, HSYA pretreatment significantly attenuated SAP-related pancreatic and lung tissue damage and the activities of the inflammatory factors TNF-α, IL-6 and MPO in BALF. In addition, HSYA promoted the expression of the antioxidant protein heme oxygenase-1 and blocked the activation of the NF-κB signaling pathway. Conclusions:HSYA exerts anti-inflammatory and antioxidant activities to inhibit SAP-related lung injury, which indicated that HSYA may be a potential therapeutic drug for SAP-induced lung injury.

Objective:To study the influence of serum triggering receptor expressed on myeloid cells 1(TREM-1)level on prognosis in elderly patients with sepsis and acute respiratory distress syndrome(ARDS).Methods:A total of 100 elderly patients with sepsis were selected as the research objects.All the patients with sepsis were divided into sepsis ARDS group and sepsis non-ARDS group.General data and TREM-1 level were compared between the two groups.The patients with sepsis ARDS were divided into death group and survival group according to the survival status during the 28-day follow-up.TREM-1 level, acute physiology and chronic health evaluation(APACHE)Ⅱ score and SOFA score were compared between the two groups.The correlation between serum TREM-1 level and procalcitonin(PCT), APACHE Ⅱ score and SOFA score was analyzed.The survival rate of high TREM-1 level group and low TREM-1 level group was compared.Results:The age, white blood cell(WBC), PCT, APACHE Ⅱ score, SOFA score and TREM-1 level of sepsis ARDS patients were significantly higher than those of non-ARDS patients( t=2.722, 6.088, 11.55, 6.889, 4.661, 6.122, all P<0.05). The incidence of sepsis ARDS patients with chronic obstructive pulmonary disease was significantly higher than that of non-ARDS patients( χ2=7.895, P<0.05). Serum TREM-1 level, APACHE Ⅱ score and SOFA score of ARDS patients in death group were significantly higher than those in survival group( t=3.293, 6.173, 4.255, all P<0.05). Serum TREM-1 level was positively correlated with PCT, APACHE Ⅱ score and SOFA score( t=0.553, 0.602, 0.636, P<0.001). The Kaplan-Meier survival curve showed that the survival rate of high TREM-1 level group was significantly lower than that of low TREM-1 level group( χ2=3.999, P=0.036). Cox regression analysis showed that TREM-1 level was a risk factor for the prognosis of ARDS patients with sepsis( HR=1.893, 95% CI: 1.049-3.414). Conclusions:Serum TREM-1 level is significantly increased in elderly patients with sepsis ARDS, which is closely related to the prognosis and can be used as a potential prognostic biomarker.

Objective: To investigate serum level changes of heart-type fatty acid-binding protein(H-FABP)and S100 calcium-binding protein B(S-100B)protein in elderly patients with chronic heart failure and their clinical significance. Methods: A total of 160 patients with chronic heart failure treated at our hospital were recruited, and 80 healthy individuals receiving regular check-ups were enrolled as normal controls.Serum levels of H-FABP and S-100B and cardiac function index scores were compared between patients with different cardiac function grades.Correlations of serum H-FABP and S-100B levels with N-terminal pro-B-type natrlure tiepeptide(NT-proBNP)and with cardiac function index scores in heart failure patients were analyzed.The sensitivity, specificity and accuracy of serum H-FABP, S-100B and NT-proBNP for heart failure detection were compared. Results: Serum levels of H-FABP, S-100B and NT-proBNP in elderly patients with chronic heart failure were elevated with increased cardiac function grading(F=9.823, 11.573 and 13.056, P=0.013, 0.000 and 0.000), and serum levels of H-FABP, S-100B and NT-proBNP were higher in elderly patients with heart failure than in the control group(P<0.05). Serum levels of H-FABP and S-100B were positively correlated with serum NT-proBNP levels, cardiac function grading and left ventricular end-diastolic diameter(LVEDd)(r=0.527, 0.510 and 0.487, P=0.008, 0.003 and 0.002; r=0.604, 0.496 and 0.533, P=0.006, 0.005 and 0.003), and were negatively correlated with left ventricular ejection fraction(LVEF)(r=-0.536 and-0.528, P=0.005 and 0.008). The sensitivity, specificity and accuracy of serum H-FABP combined with S-100B for heart failure detection were 93.2%, 91.6% and 95.7%, respectively. Conclusions Serum levels of H-FABP and S-100B are high in elderly patients with heart failure, and they are correlated with serum NT-proBNP levels, cardiac function grading and LVEDd.H-FABP combined with S-100B has a high positive rate for heart failure detection.