Background Selected patients with advanced non-small cell lung cancer (NSCLC) benefit from immunotherapy, especially immune checkpoint inhibitors such as PD-1 (programmed cell death protein 1) inhibitor. Peripheral blood biomarkers would be most convenient to predict treatment outcome and immune-related adverse events (irAEs) in candidate patients. This study explored associations between inflammation-related peripheral blood markers and onset of irAEs and outcome in patients with advanced NSCLC receiving PD-1 inhibitors. Methods A retrospective analysis was conducted of 102 patients with advanced NSCLC receiving PD-1 inhibitors from January 2017 to May 2019. Cox regression models were employed to assess the prognostic effect of low/high neutrophil/ lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and prognostic nutrition index (PNI) on overall survival (OS) and progression-free survival (PFS). Logistic regression models were used to analyze the correlation between peripheral blood markers and the onset of irAEs. Result NLR < 5, LDH < 240 U/L, or PNI ≥ 45 was favorably associated with significantly better outcomes compared with higher, higher, or lower values, respectively. The multivariate analysis determined that these parameters were independently associated with both better PFS (p = 0.049, 0.046, 0.014, respectively) and longer OS (p = 0.007, 0.031, < 0.001, respectively). Patients with three favorable factors among NLR, LDH, and PNI had better PFS and OS than did those with two, one, or none. PNI and NLR were associated with the onset of irAEs. Conclusion In patients with advanced NSCLC treated with PD-1 inhibitors, pretreatment NLR, LDH, and PNI may be useful predictive markers of clinical outcome and irAEs.

Streptococcus suis is one of the most important bacterial pathogens in the porcine industry and also a zoonotic agent. Serotype 9 is becoming one of the most prevalent serotypes within the S. suis population in certain European countries. In the present study, serotype 9 strains isolated from a country where infection due to this serotype is endemic (Spain), were compared to those recovered from Canada, where this serotype is rarely isolated from diseased pigs. For comparison purposes, strains from Brazil and the only strain isolated from a human case, in Thailand, were also incorporated. Firstly, sequence types (STs) were obtained followed by detection of putative virulence factors. Phylogenetic trees were constructed using the non-recombinant single nucleotide polymorphisms from core genomes of tested strains. Most Spanish strains were either ST123 or ST125, whereas Canadian strains were highly heterogeneous. However, the distribution of putative virulence factors was similar in both groups of strains. The fact that ST16 strains harbored more putative virulence genes and shared greater similarity with the genome of human serotype 2 strains suggests that they present a higher zoonotic and virulence potential than those from Canada and Spain. More than 80% of the strains included in this study carried genes associated with resistance to tetracycline, lincosamides and macrolides. Serotype 9 strains may be nearly 400 years old and have evolved in parallel into 2 lineages. The rapid population expansion of dominant lineage 1 occurred within the last 40 years probably due to the rapid development of the porcine industry.Electronic supplementary materialThe online version of this article (10.1186/s13567-017-0498-2) contains supplementary material, which is available to authorized users.

Corynebacterium striatum is an emerging multidrug-resistant (MDR) pathogen that occurs primarily among immunocompromised and chronically ill patients. However, little is known about the genomic diversity of C. striatum, which contributes to its long-term persistence and transmission in hospitals. In this study, a total of 192 C. striatum isolates obtained from 14 September 2017 to 29 March 2018 in a hospital in Beijing, China, were analyzed by antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing was conducted on 91 isolates. Nearly all isolates (96.3%, 183/190) were MDR. The highest resistance rate was observed for ciprofloxacin (99.0%, 190/192), followed by cefotaxime (90.6%, 174/192) and erythromycin (89.1%, 171/192). PFGE separated the 192 isolates into 79 pulsotypes, and differences in core genome single-nucleotide polymorphisms (SNPs) partitioned the 91 isolates sequenced into four clades. Isolates of the same pulsotype were identical or nearly identical at the genome level, with some exceptions. Two dominant subclones, clade 3a, and clade 4a, were responsible for the hospital-wide dissemination. Genomic analysis further revealed nine resistance genes mobilized by eight unique cassettes. PFGE and whole-genome sequencing revealed that the C. striatum isolates studied were the result mainly of predominant clones spreading in the hospital. C. striatum isolates in the hospital progressively acquired resistance to antimicrobial agents, demonstrating that isolates of C. striatum may adapt rapidly through the acquisition and accumulation of resistance genes and thus evolve into dominant and persistent clones. These insights will be useful for the prevention of C. striatum infection in hospitals.

Streptococcus suis (S. suis) is an important swine pathogen and an emerging zoonotic agent. Most clinical S. suis strains express capsular polysaccharides (CPS), which can be typed by antisera using the coagglutination test. In this study, 79 S. suis strains recovered from diseased pigs in Canada and which could not be typed using antisera were further characterized by capsular gene typing and sequencing. Four patterns of cps locus were observed: (1) fifteen strains were grouped into previously reported serotypes but presented several mutations in their cps loci, when compared to available data from reference strains; (2) seven strains presented a complete deletion of the cps locus, which would result in an inability to synthesize capsule; (3) forty-seven strains were classified in recently described novel cps loci (NCLs); and (4) ten strains carried novel NCLs not previously described. Different virulence gene profiles (based on the presence of mrp, epf, and/or sly) were observed in these non-serotypeable strains. This study provides further insight in understanding the genetic characteristics of cps loci in non-serotypeable S. suis strains recovered from diseased animals. When using a combination of the previously described 35 serotypes and the complete NCL system, the number of untypeable strains recovered from diseased animals in Canada would be significantly reduced.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-017-0417-6) contains supplementary material, which is available to authorized users.

Streptococcus suis is an important pathogen of pigs and may cause serious disease in humans. Serotyping is an important tool for detection and epidemiological studies of S. suis. Thirty-three reference serotypes and nine novel cps loci (NCLs) are recognized in S. suis. To gain a better understanding of the prevalence and genetic characteristics of NCLs, we investigated the serotype identity of 486 isolates isolated between 2013 and 2015 in China by capsular gene typing methods. Two hundred seventy-six isolates carried NCLs belonging to 16 groups, 8 of which appear to have not been reported previously. These isolates showed autoagglutination, polyagglutination, or nonagglutination with reference antisera and thus were nonserotypeable. Almost all isolates carrying the unknown NCLs were encapsulated, with various capsular thicknesses, indicating that they are most likely novel serotypes. To simultaneously identify the currently recognized 17 NCLs, an 18-plex detection system using the Luminex xTAG universal array technology was developed. Our data also provide valuable genetic information for monitoring the variations within NCLs by investigating the genetic characteristics of different subtypes within NCLs. IMPORTANCENonserotypeable Streptococcus suis isolates have been reported in many studies, and 9 novel cps loci (NCLs) have already been identified in nonserotypeable isolates. Moreover, novel cps loci are continually being found. The main purpose of this study was to investigate the prevalence and characteristics of NCLs in S. suis isolates recovered between 2013 and 2015 in China. This study provides valuable genetic information for monitoring the variations within NCLs. Meanwhile, a fast and cost-effective 18-plex detection system that can simultaneously identify the currently recognized 17 NCLs was developed in this study. This system will serve as a valuable tool for detecting known and identifying additional novel cps loci among nonserotypeable S. suis isolates. Streptococcus suis is an important pathogen of pigs and may cause serious disease in humans (1-3). Clinically healthy pigs can carry S. suis in their nasopharynx, contributing to the dissemination of this pathogen (4, 5). Moreover, a potential role of isolates from healthy pigs is as donors to transfer the new adaptive phenotypes to pathogenic isolates (6). The capsular polysaccharide (CPS) shields S. suis from host phagocytes and is a major virulence factor (7). Antisera to CPSs are used to distinguish antigenic differences among them. Serotyping is also an important epidemiological method for S. suis surveillance. This reflects the importance of including isolates from healthy pigs to better understand the diversity and evolution of CPSs in S. suis populations.A total of 35 serotypes (types 1 through 34 and type 1/2) of S. suis have been identified by different studies in the 1980s and 1990s (8-11). In 2005, strains of serotypes 32 and 34 were reclassified as Streptococcus orisratti (12). The CPS synthesis genes are known to be clustered ...

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Neutrophil extracellular traps (NETs) are closely related to cancer progression. NETs-related lncRNAs play crucial roles in non-small-cell lung cancer (NSCLC) but there have been no systematic studies regarding NETs-related long noncoding RNA (lncRNA) signatures to forecast the prognosis of NSCLC patients. It’s essential to build commensurate NETs-related lncRNA signatures. The expression profiles of prognostic mRNAs and lncRNAs and relevant clinical data of NSCLC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The NETs-related genes came from the results of our transcriptome RNA microarray data. The co-expression network of lncRNAs and NETs-related genes was structured to confirm NETs-related lncRNAs. The 19 lncRNAs correlated with overall survival (OS) were selected by exploiting univariate Cox regression ( P < 0.05). Lasso regression and multivariate Cox regression ( P < 0.05) were utilized to develop a 12-NETs-related lncRNA signature. We established a risk score based on the signature, which suggested that patients in the high-risk group displayed significantly shorter OS than patients in the low-risk group ( P < 0.0001, P = 0.0023 respectively in the two cohorts). The risk score worked as an independent predictive factor for OS in both univariate and multivariate Cox regression analyses (HR> 1, P < 0.001). Additionally, by RT-qPCR, we confirmed that NSCLC cell lines have higher levels of the three adverse prognostic NETs-related lncRNAs than normal lung cells. The expression of lncRNAs significantly increases after NETs stimulation. In short, the 12 NETs-related lncRNAs and their model could play effective roles as molecular markers in predicting survival for NSCLC patients.

Background Pulmonary infections caused by non-diphtheriae corynebacteria are increasing. However, rapid identification of Corynebacterium species poses a challenge due to the low genetic variation within the genus. Methods Three reference strains and 99 clinical isolates were used in this study. A qPCR followed by high-resolution melting (HRM) targeting ssrA was performed to simultaneously identify C. striatum, C. propinquum and C. simulans. To further evaluate this assay’s performance, 88 clinical sputum samples were tested by HRM and the detection results were compared with those of the traditional culture method and multiple cross-displacement amplification (MCDA) assay. Results The melting curve produced by a pair of universal primers generated species-specific HRM curve profiles and could distinguish the three target species from other related bacteria. The limit of detection of HRM assay for DNA from the three purified Corynebacterium species was 100 fg. Compared with the culture method, HRM detected 22 additional positive specimens, representing a 23.9% relative increase in detection rate. The HRM assay had 98.4% (95% confidence interval [CI], 90.5–99.9%) sensitivity and 100% (95% CI, 82.8–100%) specificity. Additionally, 95.5% concordance between HRM and MCDA (κ = 0.89 [95% CI, 0.79–0.99]) was noted. Conclusions The HRM assay was a simple, rapid, sensitive, and specific diagnostic tool for detecting C. striatum, C. propinquum, and C. simulans, with the potential to contribute to early diagnosis, epidemiological surveillance, and rapid response to outbreak.