With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22,774 and 84,572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.

Neuroinflammation is initiated in response to ischemic stroke, generally with the hallmarks of microglial activation and collateral brain injury contributed by robust inflammatory effects. Triggering receptor expressed on myeloid cells (TREM)-1, an amplifier of the innate immune response, is a critical regulator of inflammation. This study identified that microglial TREM-1 expression was upregulated following cerebral ischemic injury. After pharmacologic inhibition of TREM-1 with synthetic peptide LP17, ischemia-induced infarction and neuronal injury were substantially alleviated. Moreover, blockade of TREM-1 can potentiate cellular proliferation and synaptic plasticity in hippocampus, resulting in long-term functional improvement. Microglial M1 polarization and neutrophil recruitment were remarkably abrogated as mRNA levels of M1 markers, chemokines, and protein levels of myeloperoxidase and intracellular adhesion molecule-1 (ICAM-1) were decreased by LP17. Mechanistically, both in vivo and in vitro, we delineated that TREM-1 can activate downstream pro-inflammatory pathways, CARD9/NF-κB, and NLRP3/caspase-1, through interacting with spleen tyrosine kinase (SYK). In addition, TREM-1-induced SYK initiation was responsible for microglial pyroptosis by elevating levels of gasdermin D (GSDMD), N-terminal fragment of GSDMD (GSDMD-N), and forming GSDMD pores, which can facilitate the release of intracellular inflammatory factors, in microglia. In summary, microglial TREM-1 receptor yielded post-stroke neuroinflammatory damage via associating with SYK.

No abstract

Association studies on the MTHFR polymorphisms (C677T and A1298C) in colorectal cancer (CRC) and colorectal adenoma have shown conflicting results. We performed a meta-analysis to better assess the purported associations. Overall, the 677T allele (10,131 patients and 15,362 controls) showed a small but significant protective effect against CRC compared to the 677C allele [P=0.0003, odds ratio (OR)=0.93; 95% confidence interval (CI) 0.89-0.98, P=0.22 (for heterogeneity)] for a worldwide population. Metaanalyses of other genetic contrasts suggested that the 677T allele is more likely to affect CRC in a recessive genetic model worldwide (P<0.0001, OR=0.86; 95% CI 0.76-0.96, P=0.06) and in Asians (P=0.0005, OR=0.75; 95% CI 0.64-0.88, P=0.71). Similarly, we found a significantly decreased risk of CRC for 1298C polymorphism (4,764 CRC patients and 6,592 controls) for a recessive genetic model worldwide (P=0.005, OR=0.81; 95% CI 0.70-0.94, P=0.40) and in Caucasians (P=0.04, P=0.35). No evidence of association of C677T (4,616 patients and 6,338 controls) and A1298C (1,272 patients and 1,684 controls) with colorectal adenoma were found. The evidence accumulated suggests that MTHFR may represent a low-penetrance susceptible gene for CRC, and that the two polymorphisms might protect against colorectal adenoma developing into cancer. A larger single study is required to further evaluate gene-gene and geneenvironment interactions for MTHFR polymorphisms and the cancer risk in a specific population.

The molecular mechanisms that regulate human blood vessel formation during early development are largely unknown. Here we used human ESCs (hESCs) as an in vitro model to explore early human vasculogenesis. We demonstrated that stromal cell-derived factor-1 (SDF-1) and CXCR4 were expressed concurrently with hESC-derived embryonic endothelial differentiation. Human ESC-derived embryonic endothelial cells underwent dose-dependent chemotaxis to SDF-1, which enhanced vascular network formation in Matrigel. Blocking of CXCR4 signaling abolished capillary-like structures induced by SDF-1. Inhibition of the SDF-1/CXCR4 signaling pathway by AMD3100, a CXCR4 antagonist, disrupted the endothelial sprouting outgrowth from human embryoid bodies, suggesting that the SDF-1/ CXCR4 axis plays a critical role in regulating initial vessel formation, and may function as a morphogen during human embryonic vascular development. STEM CELLS 2007;25: 392-401

eWe report the first OXA-181-producing strain in China. bla OXA-181 was found in sequence type 410 (ST410) Escherichia coli strain WCHEC14828 from a Chinese patient without recent travel history. Genome sequencing and conjugation experiments were performed. bla OXA-181 was carried on a 51-kb self-transmissible IncX3 plasmid and was linked with qnrS1, a quinolone resistance gene. bla OXA-181 was introduced onto the IncX3 plasmid from a ColE2-type plasmid, and IncX3 plasmids have the potential to mediate the dissemination of bla OXA-181 .

No abstract

The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility. However, association studies on the XRCC3 polymorphisms (4541A4G, Thr 241 Met, 17893A4G) in cancer have shown conflicting results. Therefore, we performed a meta-analysis to better assess the purported associations. Forty eight eligible case-control studies including 24 975 cancer patients and 34 209 controls were selected for our meta-analysis. Overall, individuals carrying the XRCC3 Met/Met genotype showed a small cancer risk under a recessive genetic model. The subgroup and metaregression analysis demonstrated different scenarios concerning the XRCC3 Met/Met genotype's role in cancer susceptibility for different subgroups. Specially, there was a significantly increased risk of breast cancer (OR, 1.14; P ¼ 0.0004; 95% CI, 1.06 -1.23; P ¼ 0.37 for heterogeneity), elevated but not significant risk of cancer for head and neck, bladder, surprisingly, a significantly decreased risk of non-melanoma skin cancer (OR, 0.76; P ¼ 0.007; 95% CI, 0.62-0.93; P ¼ 0.61 for heterogeneity). A significantly elevated risk of cancer was observed in population-based case-control studies but not in nested or hospital based studies. Similarly, we found a significantly increased risk of cancer for A4541G and a decreased risk for A17893G under dominant genetic models. Our meta-analysis results support that the XRCC3 might represent a lowpenetrance susceptible gene especially for cancer of breast, bladder, head and neck, and non-melanoma skin cancer. A single larger study should be required to further evaluate gene -gene and geneenvironment interactions on XRCC3 polymorphisms and tissue-specific cancer risk in an ethnicity specific population.