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OBJECTIVE@#To explore the protective effect of amphiregulin (Areg) on acute respiratory distress syndrome (ARDS) in mice and its underlying mechanism.@*METHODS@#(1) Male C57BL/6 mice aged 6-8 weeks were selected for animal experiments and divided into 3 groups (n = 10) according to the random number table method, which includes sham-operated group (Sham group), ARDS model group [ARDS model in mice was established by intratracheal instillation of lipopolysaccharide (LPS) 3 mg/kg] and ARDS+Areg intervention group [recombinant mice Areg (rmAreg) 5 μg was injected intraperitoneally 1 hour after LPS modeling]. The mice were sacrificed at 24 h after LPS injection lung histopathological changes were observed under hematoxylin-eosin (HE) staining and scored for lung injury; oxygenation index and wet/dry ratio of lung tissue were measured; the content of protein in bronchoalveolar lavage fluid (BALF) was detected by bicinchoninic acid (BCA) method, the level of inflammatory factors interleukins (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) in BALF were measured by enzyme-linked immunosorbent assay (ELISA). (2) Mice alveolar epithelial cell line MLE12 cells were obtained and cultured for experiment in vitro. Blank control group (Control group), LPS group (LPS 1 mg/L) and LPS+Areg group (rmAreg 50 μg/L was added 1 hour after LPS stimulation) were set. The cells and culture fluid were collected at 24 hours after LPS stimulation, and the apoptosis level of MLE12 cells was detected by flow cytometry; the activation level of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and the expressions of apoptosis-related proteins Bcl-2 and Bax in MLE12 cells were detected by Western blotting.@*RESULTS@#(1) Animal experiments: compared with the Sham group, the lung tissue structure of ARDS model group was destroyed, the lung injury score was significantly increased, the oxygenation index was significantly decreased, the wet/dry weight ratio of lung was significantly increased, and the levels of protein and inflammatory factors in BALF were significantly increased. Compared with ARDS model group, lung tissue structure damage was reduced, pulmonary interstitial congestion, edema and inflammatory cell infiltration were significantly reduced, and lung injury score was significantly decreased (scores: 0.467±0.031 vs. 0.690±0.034) in ARDS+Areg intervention group. In addition, oxygenation index in ARDS+Areg intervention group was significantly increased [mmHg (1 mmHg ≈ 0.133 kPa): 380.00±22.36 vs. 154.00±20.74]. Lung wet/dry weight ratio (5.40±0.26 vs. 6.63±0.25), protein and inflammatory factors levels in BALF [protein (g/L): 0.42±0.04 vs. 0.86±0.05, IL-1β (ng/L): 30.00±2.00 vs. 40.00±3.65, IL-6 (ng/L): 190.00±20.30 vs. 581.30±45.76, TNF-α (ng/L): 30.00±3.65 vs. 77.00±4.16], and the differences were statistically significant (all P < 0.01). (2) Cell experiments: compared with the Control group, the number of apoptotic MLE12 cells was significantly increased in the LPS group, and the levels of PI3K phosphorylation, anti-apoptotic gene Bcl-2 level and pro-apoptotic gene Bax level were increased in MLE12 cells. Compared with the LPS group, the number of apoptosis in MLE12 cells was significantly reduced in the LPS+Areg group after administration of rmAreg treatment [(17.51±2.12)% vs. (36.35±2.84)%], and the levels of PI3K/AKT phosphorylation and Bcl-2 expression in MLE12 cells were significantly increased (p-PI3K/PI3K: 2.400±0.200 vs. 0.550±0.066, p-AKT/AKT: 1.647±0.103 vs. 0.573±0.101, Bcl-2/GAPDH: 0.773±0.061 vs. 0.343±0.071), and Bax expression was significantly suppressed (Bax/GAPDH: 0.810±0.095 vs. 2.400±0.200). The differences were statistically significant (all P < 0.01).@*CONCLUSIONS@#Areg could alleviate ARDS in mice by inhibiting the apoptosis of alveolar epithelial cells through activating PI3K/AKT pathway.
Subject(s)
Male , Animals , Mice , Mice, Inbred C57BL , Tumor Necrosis Factor-alpha , Amphiregulin , Lung Injury , Proto-Oncogene Proteins c-akt , Interleukin-6 , Lipopolysaccharides , Phosphatidylinositol 3-Kinases , bcl-2-Associated X Protein , Respiratory Distress Syndrome, NewbornABSTRACT
OBJECTIVE： To investigate and analyze medication information labeling in package inserts of anticancer drugs， and to provide reference for clinical rational use. METHODS： The package inserts of anticancer drugs were collected from drug catalogues of 3 Third Grade Class A hospitals in Nanjin. Common problems of drug package inserts （whether the main contents arweree contradictory or not and whether the contents were fully expressed， etc.）， complete specific labeling items （detailed contents of “ADR” “contraindication” “precautions” and other items）， detailed intravenous injection dispensing guidance （solvent selection， precautions during dispensing， etc.）， package insert labeling difference of drugs with same general name and route of administration were evaluated according to Drug Package Inserts and Label Management Regulation，Regulations for Chemical Drugs and Biological Products for Treatment. RESULTS： A total of 157 package inserts for anticancer drugs were collected and divided into domestic drugs （80 pieces） and imported drugs （77 pieces） according to the source as well as also divided into oral preparation （44 pieces） and injection （113 pieces）. The common problems of package inserts for anticancer drugs contained contradictory main contents， incomplete description， Chinese character errors， missing items and simple description of drug interactions， etc. Compared with domestic or oral anticancer drugs， the labeling rate of each item in the import or injection anticancer drug package inserts was higher， but specific labeling items such as prevention and treatment of vomiting （＜20％） under “precautions” and interference of drugs on clinical tests （＜40％） were lower. The labeling rate of serious ADR after large dose or long-term use was all less than 41％ under the item of “drug overdose” （except for imported drugs）. The labeling rate of intravenous dispensing guidance of imported anticancer drug injection package inserts about preparations was higher than that of domestic ones. There were differences in labeling items as “precautions” （30/56，53.57％）， “pharmacological toxicology” （29/56，51.79％）， “contraindication” （26/56，46.43％） among 56 groups of drug package inserts with same general name and route of administration. CONCLUSIONS： The labeling items for drug package inserts of anticancer drugs need to be further standardized and improved. It is recommended that the relevant departments force pharmaceutical manufacturers to regularly supplement the deficiencies in the package inserts to improve the safety of drug use in clinic.
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Objective:To sum up the characteristics of cerebrospinal fluid and brain CT findings of viral encephalitis in children, and provide guidance for clinical diagnosis and treatment of viral encephalitis.Methods: 117 cases of viral encephalitis were selected in our hospital and the results were analyzed by statistical analysis of cerebrospinal fluid and CT in children with viral encephalitis in order to compare the results of cerebrospinal fluid examination and CT examination.Results:Cerebrospinal fluid examination showed that the increased intracranial pressure were 52.14%(61/117), protein>0.5 g/L are 36.75%(43/117), elevated white blood cell levels were 57.26%(67/117), the neutrophils increased 33.33% (39/117), lymphocytes increased 31.62%(37/117), and the sugar concentration <3.3 mol/L are 14.53% (17/117). Head CT in the diagnosis of abnormalities in children were 98 cases, in which 21 were mild abnormal, 57 were moderately abnormal and 20 cases were severe abnormalities. Abnormal cerebrospinal fluid diagnosis rate of 94.02% was significantly higher than the rate of CT abnormalities 83.76% and the difference was statistically significant (x2=6.231,P<0.05).Conclusion: The abnormal rates of CT examination in the diagnosis of viral encephalitis were higher in patients with viral encephalitis. The combination of the two examinations could be more comprehensive than that of the patients with the disease and focus. It could be benefit for clinical treatment.
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Objective: To study the efficiency of silencing small ubiquitin-like modifier-1(SUMO-1) induced by siRNA in hepatocellular carcinoma cell line SMMC-7721 and the growth inhibition of SMMC-7721 thereof. Methods: The SUMO-1 siRNA was transfected into SMMC-7721 by means of lipofectamine~(TM) 2000. The silencing efficiency of SUMO-1 was examined by RT-PCR and western blot. The cell growth and cell cycle were examined by MTT and flow cytometry(FCM). The cell apoptosis was detected by DeadEnd~(TM) Colorimetric TUNEL System. Results: The siRNA could significantly silence the expression of SUMO-1 in SMMC-7721.The maximal silencing rate was utmost 73.43% at 48 hours after being transfected SUMO-1 siRNA. MTT assay revealed that the cell line grew more slowly. FCM result showed that the number of G_2 stage cells was increased significantly. But apoptosis cells were not found by TUNNEL assay. Conclusion: SiRNA is a good manner to silence the expression of SUMO-1 in SMMC-7721 in vitro. Owing to the growth inhibition induced by SUMO-1 siRNA, SUMO-1 plays an important role in development of SMMC-7721.
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Objective To evaluate the efficacy of Six Sigma management for shortening the waiting time of outpatients accepting radiography and improving patient satisfaction. Methods Six Sigma management was applied to identify the key points critical to quality in the process of radiography,analyze the factors influencing the waiting time,and take targeted measures to modify the process. Results The waiting time of patients accepting radiography was reduced by an average of 25.2min and the rate of dissatisfaction was decreased by 18%. Conclusion The application of Six Sigma management can effectively shorten the waiting time of outpatients accepting radiography and increase patient satisfaction.