Clinicoradiological features associated with epidermal growth factor receptor exon 19 and 21 mutation in lung adenocarcinoma.

AIM: To retrospectively identify clinicopathological and radiological characteristics that could be independent predictors of epidermal growth factor receptor (EGFR) exon 19 and 21 mutation in surgically resected lung adenocarcinomas in a cohort of Asian patients. MATERIALS AND METHODS: Demographics, histopathology data, and preoperative chest computed tomography (CT) images were evaluated retrospectively in 471 surgically resected lung adenocarcinomas. A total of 24 CT descriptors were assessed. Univariate analyses and multivariate logistic regression analyses were performed to identify independent predicted factors of harbouring EGFR mutations. RESULTS: EGFR mutations were existed in 252 (53.5%) of 471 patients, and associated with 11 clinicoradiological features. For the model with both clinical and radiological features, the independent predictors of harbouring EGFR mutation were small maximum diameter (≤3.9 cm), non-smokers, micropapillary pattern, pleural retraction, vascular convergence, and absence of solid pattern. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.784. Multivariable logistic regression analysis indicated that non-smokers, vascular convergence, and absence of solid pattern were important independent predictors of EGFR exon 19 mutation, while non-smokers and vascular convergence were independent predictors of EGFR exon 21 mutation. The AUCs were 0.807 and 0.794, respectively. A lepidic growth pattern appeared more frequently in exon 21 mutant tumours than in exon 19 mutant group (p<0.001). CONCLUSION: CT imaging features of lung adenocarcinomas in combination with clinical variables could be used to prognosticate EGFR mutation status. The separate analysis of EGFR exon 19 or 21 mutation could further improve diagnostic performance.

RNAi in the striped stem borer, Chilo suppressalis, establishes a functional role for aminopeptidase N in Cry1Ab intoxication.

The striped stem borer, Chilo suppressalis, is a major target pest of transgenic rice expressing the Cry1Ab protein from the bacterium Bacillus thuringiensis (Bt) in China. Evolution of resistance in this pest is a major threat to the durability of Bt rice. Since Bt exerts its activity through binding to specific receptors in the midgut of target insects, identification of functional Cry1Ab receptors in the midgut of C. suppressalis larvae is crucial to evaluate potential resistance mechanisms and develop effective strategies for delaying insect resistance. In this work, we identified the putative Cry1Ab toxin-binding protein, aminopeptidase-N (APN), in the midgut of C. suppressalis by ligand blot and mass spectrometry. After cloning the full-length cDNAs encoding APN isoforms from the C. suppressalis larval midgut, we studied their spatiotemporal expression in different gut tissues and developmental stages. Furthermore, RNA interference (RNAi) against C. suppressalis aminopeptidases (CsAPNs) was employed to illustrate a functional role for CsAPNs in Cry1Ab toxicity to C. suppressalis larvae using injection and oral delivery of Stealth™ siRNA. Down-regulating the expression of CsAPNs by RNAi was closely associated with reduced susceptibility of C. suppressalis to Cry1Ab. These data provide the first direct evidence that CsAPNs participate in the mode of Cry1Ab action and may act as the functional receptor of Cry1A in C. suppressalis larvae.

Fine structure characterization of martensite/austenite constituent in low-carbon low-alloy steel by transmission electron forward scatter diffraction.

Transmission electron forward scatter diffraction and other characterization techniques were used to investigate the fine structure and the variant relationship of the martensite/austenite (M/A) constituent of the granular bainite in low-carbon low-alloy steel. The results demonstrated that the M/A constituents were distributed in clusters throughout the bainitic ferrite. Lath martensite was the main component of the M/A constituent, where the relationship between the martensite variants was consistent with the Nishiyama-Wassermann orientation relationship and only three variants were found in the M/A constituent, suggesting that the variants had formed in the M/A constituent according to a specific mechanism. Furthermore, the Σ3 boundaries in the M/A constituent were much longer than their counterparts in the bainitic ferrite region. The results indicate that transmission electron forward scatter diffraction is an effective method of crystallographic analysis for nanolaths in M/A constituents.

[Gene typing and antibiotic resistance of methicillin-resistant Staphylococcus aureus isolated from lower respiratory tract at two hospitals in Shanghai].

OBJECTIVE: To study the genotyping characteristics and antibiotic resistance of methicillin-resistant Staphylococcus aureus(MRSA) isolated from lower respiratory tract at 2 different level hospitals in Shanghai. METHODS: The subjects included 155 patients at Ruijin Hospital and Tongren Hospital between January 2013 and June 2014, including 108 males and 47 females, with a mean age of 67.8±16.5. The 155 MRSA strains were isolated from lower respiratory tract specimens and multilocus sequence typing (MLST) and spa typing were analyzed by the PCR method. The antimicrobial resistance of MRSA was tested by VITEK-32. Fisher's exact test was used for statistical analysis. RESULTS: Among the 155 strains, 28 MLST-spa molecular types were identified, of which ST764-t002(41.29%), ST239-t037(17.42%) and ST239-t030(10.32%) were the most predominant types. The MRSA strains were susceptible to linezolid, vancomycin and teicoplanin, and also had a lower resistance to trimethoprim-sulfamethoxazole and rifampin, with a susceptible rate of 83.9% and 83.2% respectively, but were highly resistant to other antibiotics. The resistance rate of ST239-t037 to trimethoprim-sulfamethoxazole was higher than that of other types, and the resistance rate of ST239-t030 to rifampin was higher than that of other types, the differences being significant(P<0.001). The mean length of hospital stay of the 155 patients was (97±84) days, and mechanical ventilation were used in 78(50.3%) patients, while 108(69.7%))patients received invasive procedures. Broad-spectrum antibiotics were used in 136 (87.1%) patients. There were differences in age, hospitalization days, smoking history, history of COPD, mechanical ventilation, and operation between the 2 hospitals(P<0.05). CONCLUSION: Most of the MRSA strains at Ruijin Hospital and Tongren Hospital between January 2013 and June 2014 were multi-drug resistant, and the susceptibility spectrum of different genotypes was different.

Epidemiology and risk factors for faecal extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) carriage derived from residents of seven nursing homes in western Shanghai, China.

Nursing homes (NHs) have been implicated as significant reservoirs of antibiotic-resistant organisms causing severe infectious disease. We investigated the prevalence and molecular epidemiology of, and risk factors for, faecal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E). A multicentre cross-sectional study was conducted in seven NHs in Shanghai between March 2014 and May 2014. Antimicrobial susceptibility testing and polymerase chain reaction were used to detect genes coding for ESBLs and carbapenemases. NH records at individual-resident level and facility level were examined for potential risk factors. Four hundred and fifty-seven Enterobacteriaceae isolates were collected of which 183 (46·92%) were colonized by ESBL-E. CTX-M enzymes (198/200, 99%) predominated, with CTX-M-14 (84/200, 42%) the most common types. Two carbapenemase producers harboured blaKPC-2. Resistance rates to carbapenems, TZP, AK, FOS, CL and TGC were low. History of invasive procedures [odds ratio (OR) 2·384, 95% confidence interval (CI) 1·318-4·310, P = 0·004], narrow-spectrum cephalosporins (OR 1·635, 95% CI 1·045-2·558, P = 0·031) and broad-spectrum cephalosporins (OR 3·276, 95% CI 1·278-8·398, P = 0·014) were independently associated with ESBL-E carriage. In conclusion, NH residents have a very high prevalence of faecal carriage of ESBL-E. Continuous and active surveillance is important, as are prudent infection control measures and antibiotic use to prevent and control the spread of these antibiotic-resistant strains.

Influence of CYP3A5 genotypes on tacrolimus dose requirement: age and its pharmacological interaction with ABCB1 genetics in the Chinese paediatric liver transplantation.

AIM: The purpose of the study was to evaluate the impact of single nucleotide polymorphisms (SNPs) of Cytochrome P450 (CYP) 3A5 and adenosine triphosphate-binding cassette B1 (ABCB1) genotypes on TAC pharmacokinetics in Chinese paediatric patients. METHOD: A total of 136 Chinese paediatric liver recipients (R) and their donors (D) were divided into groups according to their CYP3A5 genotypes [expression of *1 allele: expressor (EX) or non-expressor (NEX)]. RESULT: Both recipient and donor CYP3A5*1 alleles had impacts on the TAC pharmacokinetics after liver transplantation. EX-R/EX-D recipients required a significantly higher TAC daily dose compared with NEX-R/NEX-D (0.24 ± 0.08 vs. 0.14 ± 0.06 mg/kg/day, p < 0.01). Age was also an independent factor on TAC requirement. Compared with EX-R/EX-D, non-expressor infants or recipients over 3-years old needed < 0.2 mg/kg/day. None of the ABCB1 SNPs (1236C>T, 2677G>A/T, 3435C>T) had an impact on TAC pharmacokinetics. However, EX-R/EX-D recipients bearing the ABCB1 1236-CC genotype required a much higher TAC dose than those without this genotype (0.23 vs. 0.18 mg/kg/day, p < 0.01), who required a similar TAC dose to that of NEX-R/NEX-D children. Furthermore, EX-R/EX-D with ABCB1 1236-CC recipients exhibited an markedly higher incidence of acute rejection and transplant-related infections clinically. CONCLUSION: CYP3A5 and ABCB1-1236 genotyping, in addition to recipient age, are necessary for establishing a more accurate TAC dosage regimen in paediatric liver recipients. We should be cautious regarding the treatment of paediatric recipients with both CYP3A5-expressor and ABCB1 1236-CC genotypes with TAC, as these patients are more susceptible to acute rejection and infection.

Detection of aminoglycoside resistance related genes in multidrug-resistant Acinetobacter baumannii isolated from a single institute of Shanghai, China.

AIM: Aminoglycoside resistance is common in Acinetobacter baumannii. We investigated aminoglycoside resistance genes in clinical multidrug-resistant Acinetobacter baumannii strains isolated from the Chinese population. METHODS: One-hundred-and-seven strains of multidrug-resistant Acinetobacter baumannii were isolated from Ruijin Hospital in Shanghai, China. The minimum inhibitory concentrations (MICs) of amikacin, kanamycin, tobramycin, gentamicin, netilmicin and neomycin for these strains were determined with agar dilution method. 16S rRNA methylase genes and eight aminoglycoside modifying enzyme genes were tested via polymerase chain reaction. RESULTS: We found MICs of amikacin, kanamycin, tobramycin, gentamicin, netilmicin and neomycin in these strains with doses of ≥64 µg/mL, ≥64 µg/mL, ≥128 µg/mL, ≥128 µg/mL, ≥32 µg/mL and ≥8 µg/mL, respectively. Most of those strains showed a high-level resistance to aminoglycosides. ArmA was found in 90% (97/107) of the strains. Six modifying enzyme genes, including aac(6')-Ib, aac(6')-II, aac(3)-II, aac(3)-I, aph(3')-I and ant(3")-I were found with a positive rate of 47%, 50%, 28%, 31%, 93% and 96%, respectively. CONCLUSION: Multidrug-resistant Acinetobacter baumannii is highly resistant to aminoglycosides. Resistant genes could coexist in one strain, therefore, strict implementation of infection control measures is essential to avoid the rapid spread or outbreaks of these multidrug-resistant Acinetobacter baumannii in healthcare-associated facilities.

Baseline susceptibility of Cnaphalocrocis medinalis (Lepidoptera: Pyralidae) to Bacillus thuringiensis toxins in China.

Geographic variability in susceptibility of field-collected Cnaphalocrocis medinalis (Guenée) (Lepidoptera: Pyralidae) to Bacillus thuringiensis (Berliner) was studied to establish a geographic baseline for comparison of future population responses to the increased use of B. thuringiensis-based insect control products. Colonies of C. medinalis were established from 10 populations collected from 10 different provinces in the major rice (Oryza savita L.)-growing regions of China. Populations were evaluated for their susceptibility to Cry1Ac and Cry1Ab endotoxin proteins with the leaf-dip bioassay. The LC50 values to Cry1Ac and Cry1Ab were estimated for the 10 populations. Bioassay results indicated that the ranges of LC50 in the second instars of C. medinalis to Cry1Ac and Cry1Ab were from 3.77 to 208.22 mg ([AI])/liter and 0.22-7.05 mg ([AI])/liter, respectively. The relative ratios in susceptibility between the most susceptible and the most tolerant populations were beyond 50-fold for Cry1Ac and 30-fold for Cry1Ab. Moreover, there was a significant positive correlation between susceptibilities to the two toxins tested, suggesting that insect populations that are relatively tolerant to one protein are also relatively tolerant to the other.