Rotavirus A (RVA) is the leading cause of acute viral gastroenteritis in children under 5 years of age worldwide. G9P[8] is a common RVA genotype that has been persistently prevalent in Jiangsu, China. To determine the genetic diversity of G9P[8] RVAs, 7 representative G9P[8] strains collected from Suzhou Children’s Hospital between 2010 and 2016 (named JS2010‐JS2016) were analyzed through whole‐genome sequencing. All evaluated strains showed the Wa‐like constellation G9‐P[8]‐I1‐R1‐C1‐M1‐A1‐N1‐T1‐E1‐H1. Furthermore, phylogenetic analysis revealed that the VP7 genes of all strains clustered into lineage G9‐III and G9‐VI. With the exception of strain JS2012 (P[8]‐4), the VP4 sequences of all strains belonged to the P[8]‐3 lineage. Sequencing further revealed that amino acid substitutions were present in the antigenic regions of the VP7 and VP4 genes of all strains. Moreover, there were multiple substitutions in antigenic sites I and II of the nonstructural protein 4 (NSP4) genes, whereas the other NSP genes were relatively conserved. In conclusion, our phylogenetic analysis of these 7 G9P[8] strains suggests that RVA varied across regions and time. Therefore, our findings suggest that continued surveillance is necessary to explore the molecular evolutionary characteristics of RVA for better prevention and treatment of acute viral gastroenteritis. 相似文献
Accurate clinical staging of non-small cell lung cancer (NSCLC) is essential for developing an optimal treatment strategy. This study aimed to determine the predictive risk factors for lymph node metastasis, including both N1 and N2 metastases, in clinical T1aN0 NSCLC patients.
Methods
We retrospectively evaluated clinical T1aN0M0 NSCLC patients who showed no radiologic evidence of lymph node metastasis, and who had undergone surgical pulmonary resection with systematic mediastinal node dissection or sampling at the First Affiliated Hospital of Zhejiang University between January 2011 and June 2013. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for node metastasis.
Results
Pathologically positive lymph nodes were found in 16.2% (51/315) of the patients. Positive N1 nodes were found in 12.4% (39/315) of the patients, and positive N2 nodes were identified in 13.0% (41/315) of the patients. Some 9.2% (29/315) of the patients had both positive N1 and N2 nodes, and 3.8% (12/315) of the patients had nodal skip metastasis. Variables of preoperative radiographic tumor size, non-upper lobe located tumors, high carcinoembryonic antigen (CEA) levels and micropapillary predominant adenocarcinoma (AC) were identified as predictors for positive N1 or N2 node multivariate analysis.
Conclusions
Pathologically positive lymph nodes were common in small size NSCLC patients with clinical negative lymph nodes. Therefore, preoperative staging should be performed more thoroughly to increase accuracy, especially for patients who have the larger size, non-upper lobe located, high CEA level or micropapillary predominant ACs. 相似文献
The CagA (cytotoxin-related gene A, CagA) protein is an important factor for the pathogenicity of Helicobacter pylori (H. pylori). Although H. pylori has previously been shown to activate the NLRP3 inflammasome, it remains unclear what role CagA plays in this process. In the current study, we aimed to investigate the effect of CagA on NLRP3 activation and how it is linked to gastric cancer cell migration and invasion.
Methods
CagA positive H. pylori strain (Hp/CagA+) and CagA gene knockout mutant (Hp/ΔCagA) infected and the pcDNA3.1/CagA plasmid transfected gastric epithelial cell lines, respectively. The morphological alterations of cells under a microscope; the NLRP3 inflammasome-related markers: NLRP3, caspase-1, and ASC protein levels were detected by Western blot, IL-1β and IL-18 levels were determined by ELISA; cell migration and invasion were determined by transwell assay; and the pyroptosis levels and intracellular ROS were determined by flow cytometry analysis. Then, pretreated with 5 mM NAC for 2 h and subsequently transfected with the pcDNA3.1/CagA plasmid for 48 h, the effects of NAC pretreatment on CagA-induced NLRP3 inflammasome-related markers expression and cell pyroptosis were examined, finally assessed the effect of CagA on migration and invasion in NLRP3-silenced cells.
Results
We found that Hp/CagA+ strain infection and pcDNA3.1/CagA vector transfection result in NLRP3 inflammasome activation, generation of intracellular ROS, and increased invasion and migration of gastric cancer cells. Moreover, we found that ROS inhibition via NAC effectively blocks NLRP3 activation and pyroptosis. Silencing of NLRP3 reduces the effects of CagA on gastric cancer cell migration and invasion.
Conclusion
Our study shows that CagA can promote the invasion and migration of gastric cancer cells by activating NLRP3 inflammasome pathway. These findings provide novel insights into the mechanism of gastric cancer induction by H. pylori.