Xiangqun Fang

Heme oxygenase-1 system, inflammation and ventilator-induced lung injury.

Mechanical ventilation is an indispensable supportive intervention for acute respiratory failure. However, mechanical ventilation can provoke ventilator-induced lung injury, which remains one of the major causes of morbidity and mortality in critically ill patients. Excessive inflammatory response characterized by infiltration of inflammatory cells and overproduction of inflammatory mediators contributes to the pathogenesis of ventilator-induced lung injury. At present, apart from the protective ventilation strategy, no other pharmacological intervention is available to attenuate ventilator-induced lung injury. Heme oxygenase-1 (HO-1) is the inducible isoform of the first and rate-limiting enzyme which degrades heme into carbon monoxide, ferritin and bilirubin. Accumulating evidence suggests that HO-1 system may function as a crucial negative regulator in the modulation of inflammatory process. This anti-inflammatory action of HO-1 is mediated essentially by the regulation of the key cells involved in inflammation and restoration of the balance between pro-inflammatory and anti-inflammatory mediators. Therefore, HO-1 system represents a promising therapeutic target for intervention of ventilator-induced lung injury.

Draft Genome Sequence of Pseudomonas aeruginosa Strain ATCC 27853

Pseudomonas aeruginosa is a common bacterium that can cause disease. The versatility of Pseudomonas aeruginosa enables the organism to infect damaged tissues or those with reduced immunity which cause inflammation and sepsis. Here we report the genome sequence of the strain ATCC 27853.

Draft Genome Sequence of Escherichia coli LCT-EC106

Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the intestine of warm-blooded organisms. Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans. Here, we present the complete genome sequence of Escherichia coli LCT-EC106, which was isolated from CGMCC 1.2385.

A multi-omic analysis of an Enterococcus faecium mutant reveals specific genetic mutations and dramatic changes in mRNA and protein expression

BackgroundFor a long time, Enterococcus faecium was considered a harmless commensal of the mammalian gastrointestinal (GI) tract and was used as a probiotic in fermented foods. In recent decades, E. faecium has been recognised as an opportunistic pathogen that causes diseases such as neonatal meningitis, urinary tract infections, bacteremia, bacterial endocarditis and diverticulitis. E. faecium could be taken into space with astronauts and exposed to the space environment. Thus, it is necessary to observe the phenotypic and molecular changes of E. faecium after spaceflight.ResultsAn E. faecium mutant with biochemical features that are different from those of the wild-type strain was obtained from subculture after flight on the SHENZHOU-8 spacecraft. To understand the underlying mechanism causing these changes, the whole genomes of both the mutant and the WT strains were sequenced using Illumina technology. The genomic comparison revealed that dprA, a recombination-mediator gene, and arpU, a gene associated with cell wall growth, were mutated. Comparative transcriptomic and proteomic analyses showed that differentially expressed genes or proteins were involved with replication, recombination, repair, cell wall biogenesis, glycometabolism, lipid metabolism, amino acid metabolism, predicted general function and energy production/conversion.ConclusionThis study analysed the comprehensive genomic, transcriptomic and proteomic changes of an E. faecium mutant from subcultures that were loaded on the SHENZHOU-8 spacecraft. The implications of these gene mutations and expression changes and their underlying mechanisms should be investigated in the future. We hope that the current exploration of multiple “-omics” analyses of this E. faecium mutant will provide clues for future studies on this opportunistic pathogen.

A propensity-matched analysis of surgery and stereotactic body radiotherapy for early stage non-small cell lung cancer in the elderly

AbstractElderly patients with early stage non-small cell lung cancer (NSCLC) who undergo surgical resection are at a high risk of treatment-related complications. Stereotactic body radiation therapy (SBRT) is considered an alternative treatment option with a favorable safety profile. Given that prospective comparative data on SBRT and surgical treatments are limited, we compared the 2 treatments for early stage NSCLC in the elderly.We retrospectively collected information from the database at our geriatric institution on patients with clinical stage IA/B NSCLC who were treated with surgery or SBRT. The patients were matched using a propensity score based on gender, age, T stage, tumor location, pulmonary function (forced expiratory volume in 1 second [FEV1]% and FEV1), Charlson comorbidity score, and World Health Organization performance score. We compared locoregional control rate, recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) between the 2 treatment cohorts before and after propensity score matching.A total of 106 patients underwent surgery, and 74 received SBRT. Surgical patients were significantly younger (72.6 ± 7.9 vs 82.6 ± 4.1 years, P = 0.000), with a significantly higher rate of adenocarcinoma (P = 0.000), better Eastern Cooperative Oncology Group performance scores (P = 0.039), and better pulmonary function test results (P = 0.034 for predicted FEV1 and P = 0.032 for FEV1). In an unmatched comparison, there were significant differences in locoregional control (P = 0.0012) and RFS (P < 0.001). The 5-year OS was 69% in patients who underwent surgery and 44.6% in patients who underwent SBRT (P = 0.0007). The 5-year CSS was 73.9% in the surgery group and 57.5% in the SBRT group (P = 0.0029). Thirty-five inoperable or marginally operable surgical patients and 35 patients who underwent SBRT were matched to their outcomes in a blinded manner (1:1 ratio, caliper distance = 0.25). In this matched comparison, the follow-up period of this subgroup ranged from 4.2 to 138.1 months, with a median of 58.7 months. Surgery was associated with significantly better locoregional control (P = 0.0191) and RFS (P = 0.0178), whereas no significant differences were found in OS (5-year OS, 67.8% for surgery vs 47.4% for SBRT, P = 0.07) or CSS (67.8% for surgery vs 58.2% for SBRT, P = 0.1816).This retrospective analysis found superior locoregional control rates and RFS after surgery compared with SBRT, but there were no differences in OS or CSS. SBRT is an alternative treatment option to surgery in elderly NSCLC patients who cannot tolerate surgical resection because of medical comorbidities. Our findings support the need to compare the 2 treatments in randomized controlled trials.

Draft Genome Sequence of Serratia marcescens Strain LCT-SM213

Serratia marcescens is a species of Gram-negative, rod-shaped bacterium of the family Enterobacteriaceae. S. marcescens can cause nosocomial infections, particularly catheter-associated bacteremia, urinary tract infections, and wound infections. Here, we present the draft genome sequence of Serratia marcescens strain LCT-SM213, which was isolated from CGMCC 1.1857.

Whole-Genome Sequence of Klebsiella pneumonia Strain LCT-KP214

Klebsiella pneumoniae is a gram-negative, nonmotile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium found in the normal flora of the mouth, skin, and intestines. Here we present the fine-draft genome sequence of K. pneumoniae strain LCT-KP214, which originated from K. pneumoniae strain CGMCC 1.1736.

Comparative genomic analysis of Klebsiella pneumonia (LCT-KP214) and a mutant strain (LCT-KP289) obtained after spaceflight

BackgroundWith the development of space science, it is important to analyze the relationship between the space environment and genome variations that might cause phenotypic changes in microbes. Klebsiella pneumoniae is commonly found on the human body and is resistant to multiple drugs. To study space-environment-induced genome variations and drug resistance changes, K. pneumoniae was carried into outer space by the Shenzhou VIII spacecraft.ResultsThe K. pneumoniae strain LCT-KP289 was selected after spaceflight based on its phenotypic differences compared to the ground-control strain. Analysis of genomic structural variations revealed one inversion, 25 deletions, fifty-nine insertions, two translocations and six translocations with inversions. In addition, 155 and 400 unique genes were observed in LCT-KP214 and LCT-KP289, respectively, including the gene encoding dihydroxyacetone kinase, which generates the ATP and NADH required for microbial growth. Furthermore, a large number of mutant genes were related to transport and metabolism. Phylogenetic analysis revealed that most genes in these two strains had a dN/dS value greater than 1, indicating that the strain diversity increased after spaceflight. Analysis of drug-resistance phenotypes revealed that the K. pneumoniae strain LCT-KP289 was resistant to sulfamethoxazole, whereas the control strain, LCT-KP214, was not; both strains were resistant to benzylpenicillin, ampicillin, lincomycin, vancomycin, chloramphenicol and streptomycin. The sulfamethoxazole resistance may be associated with sequences in Scaffold7 in LCT-KP289, which were not observed in LCT-K214; this scaffold contained the gene sul1. In the strain LCT-KP289, we also observed a drug-resistance integron containing emrE (confers multidrug resistance) and ant (confers resistance to spectinomycin, streptomycin, tobramycin, kanamycin, sisomicin, dibekacin, and gentamicin). The gene ampC (confers resistance to penicillin, cephalosporin-ii and cephalosporin-i) was present near the integron. In addition, 30 and 26 drug-resistance genes were observed in LCT-KP289 and LCT-KP214, respectively.ConclusionsComparison of a K. pneumoniae strain obtained after spaceflight with the ground-control strain revealed genome variations and phenotypic changes and elucidated the genomic basis of the acquired drug resistance. These data pave the way for future studies on the effects of spaceflight.

Genome Sequence of Pseudomonas aeruginosa Strain LCT-PA220, Which Was Selected after Space Flight by Using Biolog's Powerful Carbon Source Utilization Technology

ABSTRACT To explore the changes of Pseudomonas aeruginosa in space flight, we present the draft genome sequence of P. aeruginosa strain LCT-PA220, which originated from a P. aeruginosa strain, ATCC 27853, that traveled on the Shenzhou-VIII spacecraft.

Genome Sequence of Enterococcus faecium Clinical Isolate LCT-EF128

Enterococcus faecium, an opportunistic human pathogen that inhabits the gastrointestinal tracts of most mammals, has emerged as an important opportunistic nosocomial pathogen and is a prominent cause of multiresistant nosocomial infections. Here, we report the draft genome sequence of strain LCT-EF128, isolated from clinical specimens.