1.Clinical significance on serum intestinal fatty acid binding protein and D-lactic acid levels in early intestinal injury of patients with sepsis
Xiaobin ZHANG ; Dan LIU ; Yanbai WANG ; Jing YAN ; Xiaojun YANG
Chinese Critical Care Medicine 2019;31(5):545-550
Objective To investigate the changes and clinical significances of intestinal fatty acid binding protein (I-FABP) and D-lactic acid levels in early intestinal injury of patients with sepsis and septic shock. Methods A prospective observational study was conducted. Thirty septic patients (septic group) and 30 septic shock patients (septic shock group) were admitted to the intensive care unit (ICU) of General Hospital of Ningxia Medical University from August 2018 to December 2018, and 20 healthy adults were served as healthy control group. Serum samples were collected within 24 hours after ICU admission in septic shock and septic groups, and in healthy control group during physical examination. The serum I-FABP, D-lactic acid, endotoxin, hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and lactic acid (Lac) were determined. Gender and age of all subjects, and basic diseases, the main area of infection and acute physiology and chronic health evaluationⅡ(APACHEⅡ) scores within 24 hours after ICU admission of all patients were recorded. At the same time, the survival of the patients was followed up for 28 days. Spearman correlation analysis was used to analyze the correlation between serum I-FABP, D-lactic acid and other parameters. Risk factors of death in patients with sepsis and septic shock were screened by multivariate Logistic regression analysis of bicategorized variables. Results There was no significant difference in gender or age among the groups, as well as in the proportion of basic diseases, celiac infection or non-celiac infection between the sepsis group and the septic shock group, indicating that the general clinical baseline data among the groups were comparable. Serum levels of I-FABP and D-lactic acid in the sepsis group and the septic shock group were significantly higher than those in the healthy control group [I-FABP (μg/L): 27.46 (22.52, 34.39), 36.95 (29.82, 44.24) vs. 17.93 (14.65, 22.11), D-lactic acid (mg/L): 15.32 (9.84, 38.62), 27.95 (10.01, 47.69) vs. 9.38 (8.81, 14.48), all P < 0.01]. The serum level of I-FABP in the septic shock group was significantly higher than that in the sepsis group (P < 0.05), but the difference in serum D-lactic acid level between the two groups was not statistically significant (P > 0.05). Serum I-FABP level in the celiac infection group (n = 40) was significantly higher than that in the non-celiac infection group [n = 20; μg/L: 34.76 (27.46, 43.90) vs. 25.71 (20.55, 37.77), P < 0.01], but the difference in serum D-lactic acid level was not statistically significant [mg/L: 25.13 (9.83, 40.55) vs. 30.36 (10.17, 50.00), P > 0.05]. There was no significant difference in serum I-FABP or D-lactic acid levels between the survival group (n = 34) and the death group [n = 26; I-FABP (μg/L): 33.39 (25.20, 39.50) vs. 29.26 (22.50, 43.81), D-lactic acid (mg/L): 14.83 (9.71, 38.45) vs. 33.90 (11.93, 45.34), both P > 0.05]. Correlation analysis between serum I-FABP, D-lactic acid level and endotoxin, inflammatory factors, Lac and APACHEⅡ score in septic and septic shock patients showed that only D-lactic acid was significantly positively correlated with TNF-α and Lac (r values were 0.455 and 0.406, respectively, both P < 0.01), while I-FABP was not correlated with endotoxin, inflammatory factors, Lac or APACHEⅡscore. Multivariable Logistic regression analysis showed the APACHEⅡ score was an independent risk factor to affect the prognosis (death for 28 days) of septic and septic shock patients [odds ratio (OR) = 1.248, 95% confidence interval (95%CI) = 1.091-1.427, P = 0.001], while I-FABP, D-lactic acid, endotoxin, hs-CRP, TNF-α, IL-6, and Lac had no impact on 28-day prognosis of patients. Conclusion Serum I-FABP and D-lactic acid levels can evaluate early intestinal injury in patients with sepsis and septic shock, but neither of them is related to the prognosis of patients.
2.Brucella suis vaccine strain S2 induces apoptosis of murine BV-2 microglia cells via JNK-p53 signaling pathway
Zhao WANG ; Boya MA ; Jiayu GUO ; Ru HE ; Yanbai WANG ; Qiang LIU ; Zhenhai WANG
Chinese Journal of Microbiology and Immunology 2020;40(11):857-862
Objective:To investigate the potential mechanism by which Brucella suis vaccine strain S2 induces the apoptosis of BV-2 microglia cells, and to discover new protein targets for neurobrucellosis treatment. Methods:BV-2 microglia cells were treated with Brucella suis vaccine strain S2 for 0, 3, 6, 12 and 24 h. Western blot assay and RT-qPCR were performed to detect the expression of p-JNK and p53 at protein and mRNA levels in BV-2 microglia cells. Cell apoptosis was measured by flow cytometry. Immunofluorescence was used to analyze nuclear p-JNK. Results:Brucella suis vaccine strain S2 could promote the expression of p-JNK and p53 at both protein and mRNA levels and increase nuclear p-JNK in BV-2 microglia cells. Moreover, it could also induce the apoptosis of BV-2 microglia cells. Conclusions:Brucella suis vaccine strain S2 could promote the apoptosis of BV-2 microglia cells through activating JNK and promoting p53 expression.
3.Recent advances in developing small-molecule inhibitors against SARS-CoV-2.
Rong XIANG ; Zhengsen YU ; Yang WANG ; Lili WANG ; Shanshan HUO ; Yanbai LI ; Ruiying LIANG ; Qinghong HAO ; Tianlei YING ; Yaning GAO ; Fei YU ; Shibo JIANG
Acta Pharmaceutica Sinica B 2022;12(4):1591-1623
The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.