Acute respiratory distress syndrome (ARDS) is the leading cause of respiratory failure with high morbidity and mortality. Pulmonary surfactant (PS)-based complementary therapies have exhibited potential for ARDS healing and applied as an adjunctive therapy strategy. Coacervate (Coac) has the characteristics of softness, deformability and excellent molecular enrichment properties, and has attracted extensive attention in the biomedical field. Here PS and coacervate were combined for the potential ARDS treatment. The Coac, fabricated from polyallylamine hydrochloride (PAH) and adenosine triphosphate (ATP) by simple mixing, exhibited soft droplet property and high enrichment for dexamethasone sodium phosphate (DSP). To avoid the fusion effect of membraneless coacervate and endow it with biological functions of PS, liposomes with PS-biomimetic lipid components (PS-lipo) were further introduced to construct PS-biomimetic membranized coacervate (DSP@PS-Coac). The DSP@PS-Coac demonstrated high lung targeting effect and significant penetration efficiency after intravenous injection. Furthermore, PS-lipo replenished the endogenous PS pool and facilitated the distribution of DSP in inflammatory cells in the lung. In the ARDS mouse model, PS-Coac and DSP exerted synergetic anti-inflammatory functions, via reducing the recruitment of inflammatory neutrophils and modulating macrophages into anti-inflammatory phenotype. The overall results confirmed that DSP@PS-Coac may provide a promising delivery option for the treatment of ARDS.

Objective To investigate the molecular mechanism of Lizhong Wan in treatment of chronic atrophic gastritis (CAG) using network pharmacology and in vitro experimental method. Methods The active ingredients of Lizhong Wan were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the related targets were obtained from PubChem and Swiss Target Prediction databases. The CAG-related targets were obtained from GeneCards,OMIM and DisGeNET databases. The drug-disease common targets of Lizhong Wan and CAG were obtained by Venn tool. The interaction network of common targets of Lizhong Wan and CAG was constructed with the help of STRING database,and the drug-disease-target-pathway network was constructed with the help of Cytoscape software. Gene function and pathway enrichment analyses were performed on the common targets. The molecular docking and binding ability of the active ingredients of the drug and the key targets were predicted by using Moe software. The mice of spleen and stomach deficiency cold syndrome CAG was established. The effects of Lizhong Wan on the morphological changes of gastric tissue,apoptosis of gastric mucosa cells and the expression of messenger RNA (mRNA) and protein of the key target of CAG were observed. Results A total of 57 active ingredients of Lizhong Wan were screened,including arachidonic acid,ginsenoside Rg5,gomisin B,aposiopolamine and ginsenoside Rh2. 869 active targets of Lizhong Wan were obtained. CAG and Lizhong Wan had 47 common targets,the key common targets including tumor protein P53 (TP53),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),epidermal growth factor receptor (EGFR),B-cell lymphoma 2 (Bcl-2),etc.. A total of 135 pathways were obtained by enrichment analysis,mainly including tumor pathogenesis,proteoglycan in tumor,cholinergic synapse,phosphoinositide 3-kinase/protein kinase B signaling pathway,etc.. Molecular docking results showed that TP53,IL-6,TNF-α,EGFR,Bcl-2 had good binding activity with gomisin B and ginsenoside Rh2. Meanwhile,in vitro experimental found that the scores of spleen and stomach deficiency cold syndrome in model group were significantly higher than those in blank group. Lizhong Wan could improve the pathological changes of CAG mice,could significantly reduce the apoptosis of gastric mucosa cells,could significantly reduce the expression of mRNA and protein of TP53,IL-6,TNF-α,EGFR,Bcl-2. Conclusion The effect of Lizhong Wan in treating CAG with spleen and stomach deficiency cold syndrome may be related to regulating the expression of TP53,IL-6,TNF-α,EGFR and Bcl-2,alleviating inflammation and reducing apoptosis of gastric mucosa cells.

Objective To investigate the molecular mechanism of Lizhong Wan in treatment of chronic atrophic gastritis (CAG) using network pharmacology and in vitro experimental method. Methods The active ingredients of Lizhong Wan were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the related targets were obtained from PubChem and Swiss Target Prediction databases. The CAG-related targets were obtained from GeneCards,OMIM and DisGeNET databases. The drug-disease common targets of Lizhong Wan and CAG were obtained by Venn tool. The interaction network of common targets of Lizhong Wan and CAG was constructed with the help of STRING database,and the drug-disease-target-pathway network was constructed with the help of Cytoscape software. Gene function and pathway enrichment analyses were performed on the common targets. The molecular docking and binding ability of the active ingredients of the drug and the key targets were predicted by using Moe software. The mice of spleen and stomach deficiency cold syndrome CAG was established. The effects of Lizhong Wan on the morphological changes of gastric tissue,apoptosis of gastric mucosa cells and the expression of messenger RNA (mRNA) and protein of the key target of CAG were observed. Results A total of 57 active ingredients of Lizhong Wan were screened,including arachidonic acid,ginsenoside Rg5,gomisin B,aposiopolamine and ginsenoside Rh2. 869 active targets of Lizhong Wan were obtained. CAG and Lizhong Wan had 47 common targets,the key common targets including tumor protein P53 (TP53),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),epidermal growth factor receptor (EGFR),B-cell lymphoma 2 (Bcl-2),etc.. A total of 135 pathways were obtained by enrichment analysis,mainly including tumor pathogenesis,proteoglycan in tumor,cholinergic synapse,phosphoinositide 3-kinase/protein kinase B signaling pathway,etc.. Molecular docking results showed that TP53,IL-6,TNF-α,EGFR,Bcl-2 had good binding activity with gomisin B and ginsenoside Rh2. Meanwhile,in vitro experimental found that the scores of spleen and stomach deficiency cold syndrome in model group were significantly higher than those in blank group. Lizhong Wan could improve the pathological changes of CAG mice,could significantly reduce the apoptosis of gastric mucosa cells,could significantly reduce the expression of mRNA and protein of TP53,IL-6,TNF-α,EGFR,Bcl-2. Conclusion The effect of Lizhong Wan in treating CAG with spleen and stomach deficiency cold syndrome may be related to regulating the expression of TP53,IL-6,TNF-α,EGFR and Bcl-2,alleviating inflammation and reducing apoptosis of gastric mucosa cells.

Objective:To study the changes of β-lactam resistance of Haemophilus influenzae (Hi) strain isolated from neonatal lower respiratory tract and the molecular mechanism of β-lactam resistance.Methods:Nineteen Hi strains isolated from neonatal lower respiratory tract infection in the previous multicenter prospective epidemiological study were re-identified, and the P6, fucK and Cap genes were detected by PCR.The minimum inhibitory concentration(MIC) of ampicillin, amoxicillin clavulanic acid and cefuroxime were detected by microdilution method, and tem-1 gene, rob-1 gene and ftsI gene were sequenced and analyzed.Results:(1) Nineteen strains of Hi were confirmed to be capsule-free type by P6 gene, fucK gene and cap gene, which was non-typeable Haemophilus influenzae(NTHi). (2)Compared with 2003-2004, the MIC values of ampicillin, amoxicillin clavulanic acid and cefuroxime of NTHi isolated from the lower respiratory tract of the newborn from 2013-2014 were significantly higher( P<0.05). (3)The rates of β-lactamase producing strains during 2003-2004 and 2013-2014 were 33.33% (3/9) and 30.00% (3/10), respectively.There was no significant difference between them during 10 years ( P>0.05). The detection of the β-lactamase gene showed that the β-lactamase of the all six strains were of the tem-1 type, and the rob-1 type was not detected.(4)Only one gBLNAR strain ( n=9) was found during 2003~2004, and gBLNAR 1, gBLNAI 3, gBLPAR 3, gBLPACR 1 ( n=10)appeared during 2013~2014.(5)There were 11 amino acid substitution patterns in ftsI gene during 2013~2014, but only five amino acid substitution patterns in 2003~2004.The mutation rate of the S357N, S385T, N526K and T532S of ftsI gene significantly increased during the past ten years ( P<0.05). One strain of gBLNAR/gBLNACR resistant to ampicillin, amoxicillin clavulanic acid and cefuroxime isolated in 2014 showed D350N, S357N, M377I, S385T, L389F, A502T and N526K variation at the same time. Conclusion:Neonatal patients with lower respiratory tract NTHi infection may rapidly face the severe challenge of multiple drug resistance of β-lactam antibiotics.

Thunder-fire wonder moxibustion is one of pressing moxibustion therapies and has a very good therapeutic effect on limb pains, furuncle-carbuncle and cold syndrome. To reveal the mechanism of clinical action of ancestors’ thunder-fire wonder moxibustion and seek the physical basis of its therapeutic advantage, this study, by a series of experiments, compared heat transfer regularities of thunder-fire wonder moxibustion versus pure moxa stick in simulated biological tissues under different conditions, preliminarily revealed heat radiation and heat transfer regularities of thunder-fire wonder moxibustion, tried to find pressing strength suitable for clinical operation of pressing moxibustion and had thoughts about changes in the clinical operation of past dynasties.