eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

OBJECTIVE: To investigate the interventional effect of the Chinese herbal preparation Xi Fu Pai Chen(XFPC) on pulmonary inflammation and fibrosis in rats with silicosis. METHODS: A total of 144 adult specific pathogen free male SD rats were randomly divided into 6 groups: blank control group, silicosis model group, drug administration control group and groups of low-dose,medium-dose and high-dose XFPC, with 24 rats in each group. Lung silicosis model was established by single inhalation tracheal instillation method, which was treated with 50.0 g/L silica suspension, in groups except in the blank control group. On the 7 th day of modeling, the rats in the drug administration control group were orally given tetrandrine(5 mg/kg body weight), while those in the low-, medium-and high-dose groups were given 43, 86 and 192 g/L of XFPC by atomization inhalation once a day for 20 minutes, 5 days a week for 4 weeks. At the end of drug administration, the histopathological changes of the lung were observed. The number and classification of cells in bronchoalveolar lavage fluid(BALF)were examined, and the levels of malondialdehyde(MDA) and interferon-gamma(IFN-γ) in BALF were measured by enzyme-linked immunosorbent assay. RESULTS: On the 7 th day after modeling, the body weight in the drug administration control group and XFPC high-dose group decreased compared with the blank control group(P<0.05). On the 35 th day after modeling, the body weights of rats in the other 5 groups were lower than that in the blank control group(P<0.05). The pathological changes of lung tissue(infiltration of inflammatory cells, fibrosis and size of silicon nodule) in drug administration control group and XFPC low-dose group were better than those in silicosis model group by naked eyes and under light microscope. The lung coefficient, the proportion of neutrophils and the level of MDA and IFN-γ in BALF of the drug administration control group and XFPC low-dose group decreased(P<0.05), and the proportion of macrophages in BALF increased(P<0.05) compared with the silicosis model group. There was no significant difference in lung coefficients and the relevant indices of BALF between XFPC medium-, high-dose groups and silicosis model group(P>0.05). CONCLUSION: Low dosage XFPC can improve pulmonary fibrosis and inflammation in rats with silicosis, and its mechanism of action may be related to reducing the levels of IFN-γ and MDA in BALF.

Objective: To explore the effect of heme oxygenase-1 (HO-1) on level of reactive oxygen species (ROS) induced by zinc oxide nanoparticles (ZnO-NPs) in Human umbilical vein endothelial cells line EA.hy926. Methods: The EA.hy926 cells in logarithmic growth phase were incubated with 0.0, 2.5, 5.0, 10.0 and 15.0 mg/L ZnO-NPs respectively. The ROS level, reflected by mean fluorescence intensity (MFI), was examined by flow cytometer after 4 hours exposure, the protein expression of HO-1 which was determined by Western Blot after exposed to ZnO-NPs for 24 hours. Cells incubated with 15.0 mg/L were set as the ZnO-NPs group; a blank control group was set at the same time. Cells were pretreated with HO-1 inhibitor zinc protoporphyrin (ZnPPIx) and HO-1 activator cobalt protoporphyrin (CoPPIx), they were classified as ZnPPIx group and CoPPIx group. 15 mg/L ZnO-NPs was chosen to conduct the experiment of HO-1 activation and inhibition. Cells were classified as ZnPPIX+ ZnO-NPs group and CoPPIx+ ZnO-NPs group after pretreated with 10 μmol/L ZnPPIx or CoPPIx for 1 h, added 15 mg/L ZnO-NPs to cell culture medium. In all groups ROS levels were detected after exposed to ZnO-NPs for 4 hours, the protein expression of HO-1 was detected after exposed to ZnO-NPs for 24 hours. Results: With the increased dose of ZnO-NPs, levels of ROS and HO-1 in EA.hy926 cells were clearly elevated (the MFI of 0.0, 2.5, 5.0, 10.0 and 15.0 mg/L ZnO-NPs incubated groups was 22 627.22±718.27, 24 726.47±568.52, 31 141.75±1 312.24, 39 824.82±4 774.74, 50 569.03±1 497.63 respectively, and HO-1 relative expression were 0.16±0.01, 0.19±0.02, 0.16±0.01, 0.23±0.02, 0.92±0.06 respectively). HO-1 expression in ZnPPIx pretreatment group decreased compared with ZnO-NPs group (1.05±0.05 vs. 1.12±0.01, P<0.05), meanwhile ROS level enhanced (62 683.95±2 589.59 vs. 53 654.53±2 229.01, P<0.05). However, CoPPIx pretreatment had higher HO-1 level and lower level of ROS compared with ZnO-NPs group (HO-1: 1.74±0.11 vs. 0.22±0.03, P<0.05; ROS: 32 845.04±993.48 vs. 53 654.53±2 229.01, P<0.05). Conclusions Exposure to ZnO-NPs significantly induced ROS generation in EA.hy926 cells in a dose-dependent manner. HO-1 regulated ZnO-NPs-induced oxidative stress.

Objective To evaluate the effect of propofol post-conditioning on synaptic transmission in neurons in CA1 region during oxygen-glucose deprivation and restoration (OGD/R) in hippocampi rats .Methods Hippocampi were isolated from male Wistar rats ,aged 15-20 days ,weighing 50-60 g ,and sliced at 350μm thick . The hippocampal slices were divided into 3 groups ( n=12 each ) using a random number table :control group (group C) ,OGD/R group ,and propofol post-conditioning group (group P) .In group C ,the hippocampal slices were cultured in normal artificial cerebro-spinal fluid (nACSF ) for 7 min + 1 h . In OGD/R group , the hippocampal slices were incubated in glucose-free ACSF aerated with 95% N2 for 7 min followed by restoration of O2-glucose supply for 1 h .In group P ,the hippocampal slices were incubated in glucose-free ACSF aerated with 95% N2 for 7 min followed by incubation with normal ACSF containing propofol 1.2μg/ml for 1 h .The intensity and frequencies of spontaneous excitatory postsynaptic currents (sEPSC ) and spontaneous inhibitory postsynaptic current (sIPSC ) in neurons in CA1 region were recorded by whole-cell patch-clamp technique .Results Compared with group C ,the intensity and frequency of sEPSC were significantly increased ,while the intensity and frequency of sIPSC were decreased in OGD/R and P groups ( P<0.05) .Compared with group OGD/R ,the intensity and frequency of sEPSC were significantly decreased ,while the intensity and frequency of sIPSC were increased in group P ( P<0.05) .Conclusion The mechanism by which propofol post-conditioning attenuates OGD/R injury to hippocampi is related to inhibition of excitatory synaptic transmission and enhancement of inhibitory synaptic transmission in neurons in CA1 region .

Objective To investigate the diagnostic value of neutrophil CD64 expression for bacterial infection in children . Methods 168 children were divided into the infection group (n=133) and non-infection group(n=35) according to the results of bacterial culture .CD64 reagents from Beckman company and BD company were employed to detect CD 64 in neutrophils and lym-phocytes .Flow cytometry was used to assay their average fluorescence intensity and the CD 64 indexes were calculated .Receiver operator characteristic(ROC) curve was adopted to analyze the diagnostic performance of CD64 indexes .Results Average fluores-cence intensity of neutrophil CD64 detected by CD64 reagents from Beckman company and BD company were 46 .16 ± 29 .21 , 28 .11 ± 17 .90 ,respectively ,with statistical difference(P<0 .01) ,and their CD64 indexes were 4 .98 ± 3 .09 ,4 .89 ± 3 .53 ,respective-ly ,without statistical difference(P>0 .05) .The CD64 index of children in infection group (7 .06 ± 4 .20) was higher than that in the non-infection group(2 .93 ± 0 .79)(P<0 .01) .When CD64 index cut-off point was 3 .37 ,the sensitivity and specificity for bacterial infection diagnosis of CD64 were 93 .2% and 82 .9% ,respectively .Conclusion CD64 index may be served as an effective indicator for early diagnosis of bacterial infection in children .

Objective To detect the cellular immune and humoral immune function in infants with Mycoplasma pneumoniae(Mp) infection,and to study its change regularity and the related clinical indexes.Methods The peripheral blood samples were collected from infantile patients with MP infection.The expression of CD3,CD4 and CD8 on the surface of T lymphocyte(T-cell)were detec-ted by the flow cytometry and the concentrations of IgG,IgA and IgM in serum were detected by the automatic biochemistry analy-zer.At the same time the normal control group was set up.Results The proportion of CD3 + and CD4 + T-cell,CD4 +/CD8 + ratio and the concentration of IgG,IgA in the patient group were significantly lower than those in the control group,while the concentra-tion of IgM in the patient group were significantly lower than those in the normal children.The concentration of IgM was higher than that in the normal children;the proportion of peripheral blood CD4 + T-cell and the concentration of IgM in the low-copy group were significantly lower than those in the high-copy group.Conclusion The immune status in children with Mp infection has obvi-ous change.The immune function of T-cell is suppressed.the humoral immune function has certain turbulence.