Suchergebnisse

Yunfei Niu,1,* Wei Dong,1,* Han Guo,2 Yuhu Deng,3 Lieping Guo,1 Xiaofei An,1 Dawei He,1 Jie Wei,3 Ming Li11Department of Orthopedic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China; 2Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, People's Republic of China; 3Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People's Republic of China *These authors contributed equally to this workAbstract: Mesoporous magnesium silicate (m-MS) and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) composite (m-MPC) was synthesized by solvent casting method. The results suggest that the mechanical properties of compressive strength and elastic modulus, as well as hydrophilicity, of the m-MPC increased with increase of m-MS content in the composites. In addition, the weight loss of the m-MPC improved significantly with the increase of m-MS content during composite soaking in phosphate-buffered saline for 10 weeks, indicating that incorporation of m-MS into PCL-PEG-PCL could enhance the degradability of the m-MPC. Moreover, the m-MPC with 40 w% m-MS could induce a dense and continuous apatite layer on its surface after soaking in simulated body fluid for 5 days, which was better than m-MPC 20 w% m-MS, exhibiting excellent in vitro bioactivity. In cell cultural experiments, the results showed that the attachment and viability ratio of MG63 cells on m-MPC increased significantly with the increase of m-MS content, showing that the addition of m-MS into PCL-PEG-PCL could promote cell attachment and proliferation. The results suggest that the incorporation of m-MS into PCL-PEG-PCL could produce bioactive composites with improved hydrophilicity, degradability, bioactivity, and cytocompatibility.Keywords: PCL-PEG-PCL, degradation, cytocompatibility, cell attachment, cell proliferation

Abstract
Microwave (MW) and electromagnetic pulse (EMP) are considered environmental pollutants, both of which can induce learning and memory impairments. However, the bioeffects of combined exposure to MW and EMP have never been explored. This paper aimed to investigate the effects of combined exposure to MW and EMP on the learning and memory of rats as well as its association with ferroptosis in the hippocampus. In this study, rats were exposed to EMP, MW, or EMP and MW combined radiation. After exposure, impairment of learning and memory, alterations in brain electrophysiological activity, and damage to hippocampal neurons were observed in rats. Moreover, we also found alterations in ferroptosis hallmarks, including increased levels of iron, lipid peroxidation, and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, as well as downregulation of glutathione peroxidase 4 (GPX4) protein in the rat hippocampus after exposure. Our results suggested that either single or combined exposure to MW and EMP radiation could impair learning and memory and damage hippocampal neurons in rats. Moreover, the adverse effects caused by the combined exposure were more severe than the single exposures, which might be due to cumulative effects rather than synergistic effects. Furthermore, ferroptosis in the hippocampus might be a common underlying mechanism of learning and memory impairment induced by both single and combined MW and EMP exposure.

Gangfeng Hu,1,2 Hui Wang,1 Xiaocong Yao,1 Dawei Bi,1 Gang Zhu,1 Songchao Tang,2 Jie Wei,2 Lili Yang,3 Peijian Tong,4 Luwei Xiao4 1The First People's Hospital of Xiaoshang, Hangzhou, People's Republic of China; 2Key Laboratory of Ultra-fine Materials, Ministry of Education, East China University of Science and Technology, Shanghai, People's Republic of China; 3Department of Orthopedic Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China; 4Zhejiang Traditional Chinese Medical University, Hangzhou, People's Republic of China Abstract: Fluorapatite with low solubility is a promising biomaterial due to its structure, which is similar to hydroxyapatite. In this study a bioactive composite of nanofluorapatite (n-FA) and polyamide 12 (PA12) was fabricated. The results revealed that the mechanical properties (such as compressive strength and elastic modulus), hydrophilicity, and antibacterial properties of n-FA/PA12 composite were obviously improved by adding n-FA into PA12 as compared with PA12. In addition, cell proliferation of MC3T3-E1 cells cultured on n-FA/PA12 composite was significantly higher than with PA12, and alkaline phosphatase activity of MC3T3-E1 cells on the n-FA/PA12 composite was expressed at obviously higher levels as compared with PA12. The results suggest that n-FA/PA12 composite could support cell proliferation and differentiation, showing good cytocompatibility. Histological evaluation indicates that n-FA/PA12 composite enhances the efficiency of new bone formation with the introduction of n-FA into PA12, and the quantity of the newly formed bone for n-FA/PA12 composite is significantly higher than with PA12. In conclusion, n-FA/PA12 composite exhibits good biocompatibility and osteogenesis, which might be used for various orthopedic prostheses and dental implants. Keywords: nanofluorapatite, bioactive composites, cell behavior, orthopedic implants

Abstract
Acinetobacter baumannii has been listed as one of the most critical pathogens in nosocomial infections; however, the key genes and mechanisms to adapt to the host microenvironment lack in-depth understanding. In this study, a total of 76 isolates (from 8 to 12 isolates per patient, spanning 128 to 188 days) were longitudinally collected from eight patients to investigate the within-host evolution of A. baumannii. A total of 70 within-host mutations were identified, 80% of which were nonsynonymous, indicating the important role of positive selection. Several evolutionary strategies of A. baumannii to increase its potential to adapt to the host microenvironment were identified, including hypermutation and recombination. Six genes were mutated in isolates from two or more patients, including two TonB-dependent receptor genes (bauA and BJAB07104_RS00665). In particular, the siderophore receptor gene bauA was mutated in multiple isolates from four patients with three MLST types, and all mutations were at amino acid 391 in ligand-binding sites. With 391T or 391A, BauA was more strongly bound to siderophores, which promoted the iron-absorption activity of A. baumannii at acidic or neutral pH, respectively. Through the A/T mutation at site 391 of BauA, A. baumannii displayed two reversible phases to adapt to distinct pH microenvironments. In conclusion, we demonstrated the comprehensive within-host evolutionary dynamics of A. baumannii, and discovered a key mutation of BauA site 391 as a genetic switch to adapt to different pH values, which may represent a model in the pathogen evolutionary adaption of the host microenvironment.

Increase of myocardial oxidative stress is closely related to the occurrence and development of cardiac hypertrophy. Cordycepin, also known as 3'‐deoxyadenosine, is a natural bioactive substance extracted from Cordyceps militaris (which is widely cultivated for commercial use in functional foods and medicine). Since cordycepin suppresses oxidative stress both in vitro and in vivo, we hypothesized that cordycepin would inhibit cardiac hypertrophy by blocking oxidative stress‐dependent related signalling. In our study, a mouse model of cardiac hypertrophy was induced by aortic banding (AB) surgery. Mice were intraperitoneally injected with cordycepin (20 mg/kg/d) or the same volume of vehicle 3 days after‐surgery for 4 weeks. Our data demonstrated that cordycepin prevented cardiac hypertrophy induced by AB, as assessed by haemodynamic parameters analysis and echocardiographic, histological and molecular analyses. Oxidative stress was estimated by detecting superoxide generation, superoxide dismutase (SOD) activity and malondialdehyde levels, and by detecting the protein levels of gp91(phox) and SOD. Mechanistically, we found that cordycepin activated activated protein kinase α (AMPKα) signalling and attenuated oxidative stress both in vivo in cordycepin‐treated mice and in vitro in cordycepin treated cardiomyocytes. Taken together, the results suggest that cordycepin protects against post‐AB cardiac hypertrophy through activation of the AMPKα pathway, which subsequently attenuates oxidative stress.

INTRODUCTION: Buccal midazolam treatment is licensed in the European Union for prolonged acute convulsive seizures in children and adolescents, but the buccal pathway is often hampered by jaw clenching, hypersalivation, or uncontrolled swallowing. Midazolam formulations that are more secure, reliable, and faster for use are needed in the acute setting. Pharmacokinetics and comparative bioavailability of intranasally administered midazolam and two midazolam intravenous solutions administered buccally or intravenously in healthy adults were evaluated. METHODS: In this phase 1, open-label, randomized, single-dose, three-period, three-sequence crossover study, 12 healthy adults (19–41 years) were randomly assigned to receive 2.5 mg midazolam intranasally; 2.5 mg midazolam intravenously; 2.5 mg midazolam buccally. Blood samples were collected for 10 h post dose to determine pharmacokinetic profiles. Adverse events and vital signs were recorded. RESULTS: Intranasal administration of 2.5 mg midazolam demonstrated a more rapid median time to C(max) compared to buccal administration of midazolam (T(max), 12.6 min vs. 45 min; C(max), 38.33 ng/ml vs. 24.97 ng/ml). The antiepileptic effect of intranasal and buccal midazolam treatment lasted less than 4 h and generally did not differ from intravenously administered midazolam. No serious adverse events or deaths were reported, and no treatment-emergent adverse events led to study discontinuation. CONCLUSION: Intranasal administration of midazolam may be a preferable alternative to the currently approve buccal midazolam treatment for prolonged acute convulsive seizures in children and adolescents. TRIAL REGISTRATION: This study is registered at the Chinese Clinical Trial [http://www.chictr.org.cn] (ChiCTR2000032595) on 3 May, 2020.

Qi Wang,1 Zhanwei Wang,1 Feifei Zhang,1 Chunjiang Zhao,1 Bin Yang,2 Ziyong Sun,3 Yaning Mei,4 Feng Zhao,5 Kang Liao,6 Dawen Guo,7 Xiuli Xu,8 Hongli Sun,9 Zhidong Hu,10 Yunzhuo Chu,11 Yi Li,12 Ping Ji,13 Hui Wang1 1Department of Clinical Laboratory, Peking University People's Hospital, Beijing 100044, People's Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People's Republic of China; 3Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China; 4Department of Clinical Laboratory, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China; 5Department of Infectious Diseases, Sir Run Shaw Hospital (SRRSH), Affiliated with the Zhejiang University School of Medicine, Hangzhou 310016, People's Republic of China; 6Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, People's Republic of China; 7Department of Clinical Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China; 8Department of Clinical Laboratory, Xijing Hospital of Air Force Military Medical University, Xi'an 100191, People's Republic of China; 9Department of Clinical Laboratory, Peking Union Medical College Hospital, Beijing 100730, People's Republic of China; 10Department of Clinical Laboratory, General Hospital of Tianjin Medical University, Tianjin 300052, People's Republic of China; 11Department of Clinical Laboratory, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China; 12Department of Clinical Laboratory, Henan Provincial People's Hospital, Zhengzhou 450003, People's Republic of China; 13Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, People's Republic of ChinaCorrespondence: Hui WangDepartment of Clinical Laboratory, Peking University People's Hospital, Beijing 100044, People's Republic of ChinaTel/ Fax +86-10-88326300Email whuibj@163.comPurpose: The Chinese Meropenem Surveillance Study (CMSS) was conducted every 2 years from 2010 to 2018 to monitor the antimicrobial activity of commonly used antimicrobial agents against nosocomial gram-negative bacilli in China.Methods: From 2010 to 2018, 6,537 gram-negative bacilli were collected from 14 teaching hospitals. The minimum inhibitory concentrations (MICs) of meropenem and other antimicrobial agents were determined using the agar dilution and broth microdilution methods.Results: Continuous surveillance indicated that, except for Klebsiella pneumoniae, the susceptibility of Enterobacterales to carbapenems was relatively stable over time. Carbapenems had the highest activity against the tested isolates, with MIC90 values (MIC for 90% of organisms) ranging from 0.032 mg/L to 8 mg/L. More than 90% of bacteria were susceptible to either meropenem or imipenem; more than 80% were susceptible to ertapenem. The prevalence of extended-spectrum beta-lactamase (ESBL)-producing E. coli, K. pneumoniae, and P. mirabilis each year was 50.4– 64.3%, 18– 41.2%, and 1.9– 33.8%, respectively. The prevalence of carbapenem-resistant K. pneumoniae (CRKP) and carbapenem-resistant Acinetobacter baumannii (CRAB) continued to increase significantly over time, from 7.6% to 21.2% and 64.6% to 69.3%, respectively. The prevalence of CRKP was higher from urinary tract infections (25.4%) than from bloodstream infections (14.2%), intra-abdominal infections (14.5%), and respiratory infections (14.4%). In total, 129 CRKP isolates were evaluated by PCR; of these, 92 (71.3%) carried the blaKPC-2 gene. Colistin maintained very high in vitro antimicrobial activity against P. aeruginosa and A. baumannii (more than 95% of isolates exhibited susceptibility at all timepoints).Conclusion: The results indicate an increase in K. pneumoniae resistance to carbapenems over time, mainly owing to KPC-type carbapenemase production. A. baumannii was severely resistant to carbapenems in China. Ongoing MIC-based resistance surveillance, like CMSS, provides additional data for clinical anti-infective treatment.Keywords: CMSS, gram-negative bacilli, antimicrobial susceptibility surveillance, carbapenem-resistant