[Clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor and prognostic analysis].

OBJCTIVE: To study the clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor (cPNET), as well as the risks factors for poor prognosis. METHODS: A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with cPNET from June 2012 to September 2018. RESULTS: The 42 children had a median overall survival (OS) time of 2.0 years and a median event-free survival (EFS) time of 1.3 years; the 1-, 3-, and 5-year OS rates were 76.2%±6.6%, 41.4%±8.7%, 37.3%±8.8% respectively, and the 1-, 3-, and 5-year EFS rates were 64.3%±7.4%, 32.7%±8.0%, 28.0%±8.1% respectively. The univariate analysis showed that there were significant differences in the OS and EFS rates among the children with different patterns of surgical resection, chemotherapy cycles, and risk grades (P<0.05), and there was also a significant difference in the OS rate between the children receiving radiotherapy and those not receiving radiotherapy (P<0.05). The multivariate Cox regression analysis showed that chemotherapy cycles and risk grade were independent influencing factors for EFS and OS rates (P<0.05). The EFS and OS rates increased with the increase in chemotherapy cycles and the reduction in risk grade. CONCLUSIONS: Multimodality therapy with surgery, chemotherapy, and radiotherapy is an effective method for the treatment of cPNET in children. Early diagnosis and treatment and adherence to chemotherapy for as long as possible may improve EFS and OS rates.

[Effect of bevacizumab in treatment of children with optic pathway glioma].

OBJECTIVE: To investigate the effect of bevacizumab in the treatment of children with optic pathway glioma (OPG). METHODS: A retrospective analysis was performed for the clinical data of 30 children with OPG who underwent chemotherapy. According to whether bevacizumab was used, they were divided into conventional chemotherapy (carboplatin, vincristine and etoposide) group with 12 children and combined chemotherapy (bevacizumab, carboplatin, vincristine and etoposide) group with 18 children. The children were followed up to 6 months after chemotherapy, and the two groups were compared in terms of visual acuity and tumor size before and after chemotherapy and adverse reactions during chemotherapy. RESULTS: The combined chemotherapy group had a significantly higher proportion of children achieving tumor regression than the conventional chemotherapy group (P<0.05), while there were no significant differences between the two groups in the proportion of children with improved visual acuity or adverse reactions (P>0.05). No chemotherapy-related death was observed in either group. CONCLUSIONS: Bevacizumab combined with conventional chemotherapy can effectively reduce tumor size. Compared with conventional chemotherapy, such combination does not increase adverse reactions and can thus become a new direction for the treatment of OPG in children.

Association of Thromboembolic Risk Score with Left Atrial Thrombus and Spontaneous Echocardiographic Contrast in Non-Anticoagulated Nonvalvular Atrial Fibrillation Patients.

OBJECTIVES: The aim of the study was to examine the association of CHADS2/CHA2DS2-VASc scores with left atrial thrombus (LAT) and spontaneous echocardiographic contrast (SEC) in non-anticoagulated nonvalvular atrial fibrillation (NVAF) spontaneous patients, and to develop a new scoring system for LAT/SEC prediction. METHODS: Consecutive non-anticoagulated NVAF patients with or without LAT/SEC by transesophageal echocardiography were identified in the Guangdong General Hospital. RESULTS: Among 2,173 patients, the prevalence of LAT/SEC was 4.9%. Both predictive values of CHADS2 and CHA2DS2-VASc scores for the presence of LAT/SEC were low-to-moderate (receiver operating characteristic [ROC] = 0.591 and 0.608, respectively, p = 0.90). By multivariate analysis, non-paroxysmal AF, decreased left ventricular ejection fraction, and left atrial enlargement were positively associated with LAT/SEC, while CHADS2/CHA2DS2VASc scores were not. A new scoring system based on these 3 factors above significantly improved the discrimination for LAT/SEC (ROC = 0.792). CONCLUSIONS: CHADS2/CHA2DS2-VASc scores had limited value in predicting LAT/SEC; a new scoring system that combines AF type and echocardiographic parameters may better predict LAT/SEC as a surrogate for cardioembolic risk in NVAF patients.

The protective effects of Bacillus licheniformis preparation on gastrointestinal disorders and inflammation induced by radiotherapy in pediatric patients with central nervous system tumor.

PURPOSE: we studied the effect of Bacillus licheniformis preparation (ZCS) on CNST (central nervous system tumor) patients undergoing the gastrointestinal symptoms and inflammation induced by radiotherapy. MATERIALS AND METHODS: 160 CNST patients with craniospinal irradiation (CSI) treatment were divided into experiment and control group. The experiment group patients took one capsule per time of ZCS and three times a day until the end of radiotherapy, starting one day before radiotherapy. While the patients in control group were administrated placebo without any probiotics. Serum from one day before radiotherapy and the first day after radiotherapy were collected to measure the ET, CRP, TNF-α, IL-1ß and IL-6. RESULTS: More than 70% CNST pediatric patients suffered from different degrees of gastrointestinal symptoms after radiotherapy, including mouth ulcer, nausea, vomiting, abdominal pain and diarrhea. And there was an obviously increased of serum ET, TNF-α, IL-1ß, IL-6 and CRP after RT. Importantly, a markedly decreased of ET, CRP and inflammatory cytokines were detected in the experiment group comparing to the control group after radiotherapy, as well as the relief of the gastrointestinal symptoms. However, improvement of probiotics (or ZCS) of the survival rate of CNST children and the recurrence of tumor are not observed in this study. CONCLUSIONS: Prophylactically administrated ZCS during radiotherapy for CNST patients can relieve RT-related gastrointestinal symptoms and inflammatory reaction.

Resistance mechanisms and fitness of Salmonella Typhimurium and Salmonella Enteritidis mutants evolved under selection with ciprofloxacin in vitro.

The aim of this study was to investigate the difference in resistance mechanisms and fitness of Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE) mutants selected during the evolution of resistance under exposure to increasing ciprofloxacin concentrations in vitro. Mutations in quinolone target genes were screened by PCR. Phenotypic characterization included susceptibility testing by the broth dilution method, investigation of efflux activity and growth rate, and determination of the invasion of human intestinal epithelium cells in vitro. The two Salmonella serotypes exhibited differences in target gene mutations and efflux pump gene expression during the development of resistance. In the parental strains, ST had a competitive advantage over SE. During the development of resistance, initially, the SE strain was more competitive. However, once ciprofloxacin resistance was acquired, ST once again became the more competitive strain. In the absence of bile salts or at 0.1% bile, the growth rate of SE was initially greater than that of ST, but once ciprofloxacin resistance was acquired, ST had higher growth rates. ST strains showed decreased invasion of epithelial cells in 0.1% bile. These data indicate that ciprofloxacin-resistant ST strains are more competitive than ciprofloxacin-resistant SE strains.

CTX-M-27 Producing Salmonella enterica Serotypes Typhimurium and Indiana Are Prevalent among Food-Producing Animals in China.

Salmonella spp. is one of the most important food-borne pathogens causing digestive tract and invasive infections in both humans and animals. Extended-spectrum ß-lactamases (ESBLs) especially the CTX-M-type ESBLs are increasingly being reported worldwide and in China. These studies seldom focused on Salmonella isolates from food-producing animals. The aim of this study was to characterize the antimicrobial resistance profiles, serotypes and ESBLs and in particular, CTX-M producing Salmonella isolates from chickens and pigs in China. Salmonella isolates were identified by API20E system and polymerase chain reaction (PCR) assay; serotypes were determined using slide agglutination with hyperimmune sera; antimicrobial susceptibility was tested using the ager dilution method; the prevalence of ESBLs and PMQR genes were screened by PCR; CTX-M-producing isolates were further characterized by conjugation along with genetic relatedness and plasmid replicon type. In total, 159 Salmonella strains were identified, among which 95 strains were Salmonella enterica serovar Typhimurium, 63 strains were S. enterica serovar Indiana, and 1 strain was S. enterica serovar Enteritidis. All of these isolates presented multi-drug resistant phenotypes. Forty-five isolates carried bla CTX-M genes, the most common subtype was CTX-M-27(34), followed by CTX-M-65(7) and CTX-M-14(4). Most bla CTX-M genes were transmitted by non-typeable or IncN/IncFIB/IncP/IncA/C/IncHI2 plasmids with sizes ranging from 80 to 280 kb. In particular, all the 14 non-typeable plasmids were carrying bla CTX-M-27 gene and had a similar size. PFGE profiles indicated that CTX-M-positive isolates were clonally related among the same serotype, whilst the isolates of different serotypes were genetically divergent. This suggested that both clonal spread of resistant strains and horizontal transmission of the resistance plasmids contributed to the dissemination of bla CTX-M-9G-positive Salmonella isolates. The presence and spread of CTX-M, especially the CTX-M-27 in S. enterica serovars Typhimurium and Indiana from food-producing animals poses a potential threat for public health. Control strategies to limit the dissemination of these strains through the food chain are necessary.

High frequency of virulence genes among Escherichia coli with the blaCTX-M genotype from diarrheic piglets in China.

The purpose of this study was to characterize the virulence potential and determine the molecular epidemiology of extended-spectrum ß-lactamases (ESBLs) in CTX-M-producing Escherichia coli isolated from piglets with diarrhea in China. A total of 62 E. coli isolates were obtained among which 49 and 13 were collected from diarrheic and healthy piglets, respectively. Cefotaxime resistant strains were screened for the presence of ESBL, adhesin and exotoxin genes as well as for their biofilm-forming ability. Characterization of blaCTX-M plasmids was determined by conjugation along with the determination of genetic relatedness and plasmid replicon type. CTX-M producers were found in 36 isolates with 6 different subtypes: blaCTX-M-14,27,65 from CTX-M-9G (n=27) and blaCTX-M-55, 15,79 from CTX-M-1G (n=22). This also included 13 isolates that carried two different CTX-M genes. Thirty of 36 CTX-M producers and 12 of 13 multiple CTX-M alleles were confirmed from diarrheic piglets. The presence of the iron regulatory gene irp2 as well as EAST1 was found in 83.3% (25/30) of CTX-M-producing isolates from diarrheic piglets and these were significantly better biofilm formers. PFGE profiles of CTX-M-positive isolates indicated the spread of multidrug resistance was primarily horizontal and spread via transferable plasmids. Most blaCTX-M-9G genes (10/17) were located on the IncFIB type plasmid with sizes of 40-145 kb, while the blaCTX-M-1G (11/16) genes were located on the ∼ 100 kb IncN-type plasmid. Together, our findings demonstrate that CTX-M ESBL-producing E. coli from diarrheic piglets were associated with serious multidrug resistance, increased biofilm-forming ability and the irp2 gene of HPI. Our findings highlight the need to urgent control the spread of resistant strains through food chain.

Co-prevalance of PMQR and 16S rRNA methylase genes in clinical Escherichia coli isolates with high diversity of CTX-M from diseased farmed pigeons.

In the present study, we determined the molecular epidemiology of extended-spectrum ß-lactamases (ESBLs) in Escherichia coli isolated from diseased farmed pigeons in China. A total of 71 E. coli isolates were collected from three pigeon farms from 2011 to 2012 and screened for the presence of the ESBL genes. The ESBLs producers were further tested for the presence of PMQR-encoding genes as well as the 16S rRNA methylase gene using PCR and DNA sequence analysis. Co-transfer of plasmids encoding for ESBLs, PMQR determinants and/or 16S rRNA methylase gene was performed by conjugation into E. coli. The genetic relatedness and plasmid replicon type were determined. A total of 41 ESBLs producers were identified. Only CTX-M type ESBLs were detected, with the most common CTX-M types being CTX-M-65 (n=17), CTX-M-27 (n=11), CTX-M-55 (n=10). Thirty-eight CTX-M-positive isolates were found to harbor at least one PMQR gene, with aac(6')-Ib-cr (n=32) and oqxAB (n=21) being the most prevalent. The rmtB was the only prevalent 16S rRNA methylase gene detected in 24 (58.1%) CTX-M-positive isolates. Although most of the CTX-M producers had distinct pulsotypes, clonal transmission in the same farm was observed. blaCTX-M genes were carried by IncF alone or in combination with IncK plasmids with three different sizes, including 76.8Kb (n=20), 194Kb (n=5), 104.5Kb (n=2). PFGE profiles of CTX-M-positive E. coli isolates indicated potential horizontal spread of these multidrug resistant strains along with those CTX-M encoding genes. Our findings highlight the importance of pigeons as a reservoir of multiple antimicrobial resistance genes.

IncA/C plasmid-mediated spread of CMY-2 in multidrug-resistant Escherichia coli from food animals in China.

OBJECTIVES: To obtain a broad molecular epidemiological characterization of plasmid-mediated AmpC ß-lactamase CMY-2 in Escherichia coli isolates from food animals in China. METHODS: A total of 1083 E. coli isolates from feces, viscera, blood, drinking water, and sub-surface soil were examined for the presence of CMY-2 ß-lactamases. CMY-2-producing isolates were characterized as follows: the blaCMY-2 genotype was determined using PCR and sequencing, characterization of the blaCMY-2 genetic environment, plasmid sizing using S1 nuclease pulsed-field gel electrophoresis (PFGE), PCR-based replicon typing, phylogenetic grouping, XbaI-PFGE, and multi-locus sequence typing (MLST). RESULTS: All 31 CMY-2 producers were only detected in feces, and presented with multidrug resistant phenotypes. All CMY-2 strains also co-harbored genes conferring resistance to other antimicrobials, including extended spectrum ß-lactamases genes (blaCTX-M-14 or blaCTX-M-55), plasmid-mediated quinolone resistance determinants (qnr, oqxA, and aac-(6')-Ib-cr), floR and rmtB. The co-transferring of blaCMY-2 with qnrS1 and floR (alone and together) was mainly driven by the Inc A/C type plasmid, with sizes of 160 or 200 kb. Gene cassette arrays inserted in the class 1 or class 2 integron were amplified among 12 CMY-2 producers. CMY-2 producers belonged to avirulent groups B1 (n = 12) and A (n = 11), and virulent group D (n = 8). There was a good correlation between phylogenetic groups and sequence types (ST). Twenty-four STs were identified, of which the ST complexes (STC) 101/B1 (n = 6), STC10/A (n = 5), and STC155/B1 (n = 3) were dominant. CONCLUSIONS: CMY-2 is the dominant AmpC ß-lactamase in food animals and is associated with a transferable replicon IncA/C plasmid in the STC101, STC10, and STC155 strains.