pH-Sensitive Peptide Hydrogels as a Combination Drug Delivery System for Cancer Treatment.

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 ß-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.

High-dose dexamethasone injection disordered metabolism and multiple protein kinases expression in the mouse kidney.

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.

Incidence of Adverse Effects of Propofol for Procedural Sedation/Anesthesia in the Pediatric Emergency Population: A Systematic Review and Meta-Analysis.

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.

Microbiological study of pathogenic bacteria isolated from paediatric wound infections following the 2008 Wenchuan earthquake.

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.

[Risk factors for the occurrence and severity of crush syndrome in pediatric trauma victims after earthquake].

OBJECTIVE: To analyze the factors affecting the occurrence and severity of crush syndrome (CS) after crush injury (CI) in pediatric trauma victims in the Wenchuan earthquake. METHODS: Medical records of 98 patients who were transferred to our hospital were retrospectively reviewed. The risk factors, such as age, gender, time being besieged, type of injury, wound infection, hemodialysis, etc., which were assessed with T-test/chi(2)/Fisher's exact tests and logistic regression analysis for the occurrence of crush syndrome after crush injury. Possible risk factors influencing CS severity were analyzed. RESULTS: There were 15 patients with CS, and all these cases were from 59 patients with extremities crush injury. The incidence of CS reached 15.3% in pediatric trauma victims after earthquake and 25.4% in extremities crush injury. Six risk factors were assessed with logistic regression analysis for three outcomes relating to crush syndrome, they are age, time being szeged and closed CI, whose log-odds ratio (log-OR) respectively was 1.049, 1.221, and 0.068 (P < 0.05 for all). And no correlation was found between CS and gender, upper or lower limbs injury or wound infection. There was no significant difference in wounds infection rate between patients with open injury and those who underwent CS fasciotomy (P = 0.754), but there was significant difference between those patients who underwent CS fasciotomy and those who underwent other operative incisions (P < 0.05). Wound infection had a significant association with severity of CS (P = 0.041) as compared with other factors such as age, gender, and time being szeged. CONCLUSION: The occurrence of crush syndrome is mainly because of extremities crush injury and also has significant relations with age, time being szeged and closed crush injury in children. Infection of incisional wound after CS fasciotomy is a risk factor for aggravation of CS.

[Distribution and drug resistance of pathogenic bacteria isolated from infected wounds of children after Wenchuan earthquake].

OBJECTIVE: To investigate the distribution and the drug resistance pattern of pathogenic bacteria isolated from pediatric cases suffering from wounds infection following the Wenchuan earthquake. METHODS: Of the ninety-eight injured children, 50 had wound infection diagnosed by clinical examination. Specimens for culture were collected from the fifty injured children and the results of bacterial identification and antibiotic resistance were retrospectively reviewed. RESULTS: In the fifty injured children with wound infection, microbial growth was detected in 31 (62.0%) and 21 children suffered from mixed infections (the infection rate was 67.7%). Ninety-nine pathogens were isolated, gram positive bacteria accounted for 16.16% (16 strains), Gram negative bacteria accounted for 81.82% (81 strains), and fungus 2.02% (2 strains). Staphylococcus aureus (5 strains, 5.05%), Enterococcus faecalis (3 strains, 3.03%) and Enterococcus faecium (2 strains, 2.02%) were the primary Gram-positive bacteria identified and Gram-negative infections typically included Acinetobacter baumanii (27 strains, 27.27%), Enterobacter cloacae (18 strains, 18.18%) and Pseudomonas aeruginosa (13 strains, 13.13%). Acinetobacter baumanii was the most common organism isolated from wounds. Duration of being szeged and complications had a significant association with wound infection with Acinetobacter baumanii. Drug sensitivity tests displayed that the isolated bacteria were highly resistant to common antibiotics. One strain of Acinetobacter baumanii-calcoaceticus complex and six strains of Acinetobacter baumanii were resistant to all common antibiotics including imipenem/cilastatin. Vancomycin-resistant Gram-positive bacteria were not identified. CONCLUSION: Following the Wenchuan earthquake disaster, wound infection profiles of pediatric patients were significantly different, Acinetobacter baumanii was the main common organism isolated from wounds in contrast to the previous low isolation rate. The isolated bacteria were highly and multiple drug resistant and it was difficult to treat. Knowing the distribution and the drug resistance pattern of pathogen is of paramount importance in guiding the clinical treatment.