Conventional antitumor chemotherapeutics generally have shortcomings in terms of dissolubility, selectivity and drug action time, and it has been difficult to achieve high antitumor efficacy with single-drug therapy. At present, combination therapy with two or more drugs is widely used in the treatment of cancer, but a shortcoming is that the drugs do not reach the target at the same time, resulting in a reduction in efficacy. Therefore, it is necessary to design a carrier that can release two drugs at the same site. We designed an injectable pH-responsive OE peptide hydrogel as a carrier material for the antitumor drugs gemcitabine (GEM) and paclitaxel (PTX) that can release drugs at the tumor site simultaneously to achieve the antitumor effect. After determining the optimal gelation concentration of the OE polypeptide, we conducted an in vitro release study to prove its pH sensitivity. The release of PTX from the OE hydrogel in the medium at pH 5.8 and pH 7.4 was 96.90% and 38.98% in 7 days. The release of GEM from the OE hydrogel in media with pH of 5.8 and 7.4 was 99.99% and 99.63% in 3 days. Transmission electron microscopy (TEM) and circular dichroism (CD) experiments were used to observe the microstructure of the peptides. The circular dichroism of OE showed a single negative peak shape when under neutral conditions, indicating a β-folded structure, while under acidic conditions, it presented characteristics of a random coil. Rheological experiments were used to investigate the mechanical strength of this peptide hydrogel. Furthermore, the treatment effect of the drug-loaded peptide hydrogel was demonstrated through in vitro and in vivo experiments. The results show that the peptide hydrogels have different structures at different pH values and are highly sensitive to pH. They can reach the tumor site by injection and are induced by the tumor microenvironment to release antitumor drugs slowly and continuously. This biologically functional material has a promising future in drug delivery for combination drugs.
On 12 May 2008, the Wenchuan earthquake struck in Sichuan, China. Within 1 month after the earthquake, 98 injured children were admitted to the Children's Hospital of Chongqing Medical University. According to clinical manifestations, 50 children were diagnosed with wound infections. Wound secretions were cultured for bacteria. Pathogen distribution and drug resistance were analyzed. A total of 99 pathogens were isolated; 16 (16%) were Gram-positive bacteria and 81 (82%) were Gram-negative bacteria. The distribution of pathogens isolated within 1 month after the earthquake was different to the distribution of pathogens in 546 general hospitalized cases in the y before the earthquake. The pathogens most frequently isolated 1 month after the earthquake were Acinetobacter baumannii (27%), Enterobacter cloacae (18%) and Pseudomonas aeruginosa (13%). The pathogens most frequently isolated in the y prior to the earthquake were Escherichia coli (27%), Staphylococcus aureus (23%) and coagulase-negative staphylococci (9%). The rate of isolated drug-resistant bacteria was higher in the earthquake cases than in the general hospitalized cases. In the cases injured in the earthquake, the rates of isolation of methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing E. cloacae, E. coli and Klebsiella pneumoniae were higher than in the cases from before the earthquake. Multidrug-resistant and pandrug-resistant A. baumannii were isolated at a higher rate in cases after the earthquake than in those before the earthquake. These changes in the spectrum of pathogens and in the drug resistance of the pathogens isolated following an earthquake will provide the basis for emergency treatment after earthquakes.
Background. To investigate the incidence of adverse effects of propofol among pediatric population for sedation or anesthesia. Methods. We performed Cochrane Library, PubMed, CNKI, VIP, and Wanfang databases to research relevant literature. We did sensitivity analysis to assess the incidence of adverse effects of propofol among pediatric population for sedation or anesthesia. Results. In 132 studies, eight RCTs were included in this analysis. The result showed that adverse events (bradypnea, hypotension, hypertension, and apnea) were significantly improved in the pediatric emergency population in the propofol group, but it had no effect on the incidence of cough attacks, desaturation, agitation, stridor, and laryngospasm. Furthermore, the subgroup analysis showed that those who received propofol for had decreased adverse effects compared with the patients who received ketamine treatment ( SMD = 0.44 , 95 % CI = 0.28 , 0.67 , I 2 = 0 %, and P = 0.0002 ), which demonstrated that propofol could decrease the incidence of adverse effects compared with ketamine and ketofol. Conclusions. The study demonstrated that propofol may decrease the incidence of bradypnea, hypotension, hypertension, and apnea, but it had no effect on the incidence of cough attacks, desaturation, agitation, stridor, and laryngospasm. Furthermore, more large RCTs are needed to assess incidence of adverse effects of propofol among pediatric population.
Glucocorticoids (GCs) have been widely used in clinical treatment as anti-inflammatory, anti-shock and immunosuppressive medicines. However, the effect of excessive GCs on immune response and metabolism of kidney remains unclear. Here, we profiled the gene expression of kidney from mice with high-dose dexamethasone (DEX) treatment. A total of 1193 differentially expressed genes (DEGs) were screened in DEX treatment group compared with the saline group, including 715 down- regulated and 478 up-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of these DEGs showed extracellular matrix (ECM)–receptor interaction, cell adhesion molecules signaling pathway were significantly enriched, and that the vast majority of DEGs were involved in monocarboxylic acid metabolism, leukocyte cell–cell adhesion and fatty acid metabolism. Gene set enrichment analysis (GSEA) revealed that DEGs were strongly associated with immune-response and cell adhesion gene sets, such as Fc γ R-mediated phagocytosis, leukocyte transendothelial migration, T-cell receptor signaling pathway, cell adhesion, ECM–receptor interaction and focal adhesion-associated pathways. KEGG pathway analysis of differentially expressed kinases (DEKs) showed T-cell receptor and forkhead box class O signaling pathway were enriched. Furthermore, we found multiple protein kinases expression were dysregulated greatly after dexamethasone treatment, including classical effector of GCs stimulation-serum and GC-regulated kinase. These protein kinases are involved in multiple signaling pathways in mice kidney, such as mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. We profiled the gene expression of the kidney from high-dose dexamethasone-treated mice and provided important information for further study the mechanism of side effects of GCs in clinical therapy.
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