Intrapulmonary lymph node (stations 13 and 14) metastasis in peripheral non-small cell lung cancer.

ABSTRACT: It remains unknown whether dissecting the intrapulmonary lymph nodes (stations 13 and 14) when resecting peripheral non-small cell lung cancer (NSCLC) is necessary for accurate tumor node metastasis (TNM) staging. This study investigated intrapulmonary lymph node dissection (stations 13 and 14) on the pathological staging of peripheral NSCLC and the metastatic pattern of the lymph nodes.This retrospective study included patients with primary peripheral NSCLC who underwent radical dissection between January 2013 and December 2015. The clinical data of patients and examination results of intrapulmonary stations 12, 13, and 14 lymph nodes were analyzed.Of 3019 resected lymph nodes in a total of 234 patients (12.9/patient), 263 (8.7%) had metastasis. Ninety-nine patients had lymph node metastasis (42.3%): 40 (17.1%) were N1, 11 (4.7%) were N2, 48 (20.5%) were both N1 and N2, and 135 (57.7%) had no N1 or N2 metastasis. Sixteen (6.8%) patients had metastasis of stations 13 and/or 14. Metastasis in N1 positive patients of stations 10, 11, 12, 13, and 14 were 2.7%, 10.5%, 9.8%, 10.4%, and 8.5%, respectively. Missed detection without station 13 and 14 dissection was up to 6.8% (16/234).Dissection of stations 13 and 14 could be helpful for the identification of lymph node metastasis and for the accurate TNM staging of primary NSCLC.

Inhibitor Development against p7 Channel in Hepatitis C Virus.

Hepatitis C Virus (HCV) is the key cause of chronic and severe liver diseases. The recent direct-acting antiviral agents have shown the clinical success on HCV-related diseases, but the rapid HCV mutations of the virus highlight the sustaining necessity to develop new drugs. p7, the viroporin protein from HCV, has been sought after as a potential anti-HCV drug target. Several classes of compounds, such as amantadine and rimantadine have been testified for p7 inhibition. However, the efficacies of these compounds are not high. Here, we screened some novel p7 inhibitors with amantadine scaffold for the inhibitor development. The dissociation constant (Kd) of 42 ARD-series compounds were determined by nuclear magnetic resonance (NMR) titrations. The efficacies of the two best inhibitors, ARD87 and ARD112, were further confirmed using viral production assay. The binding mode analysis and binding stability for the strongest inhibitor were deciphered by molecular dynamics (MD) simulation. These ARD-series compounds together with 49 previously published compounds were further analyzed by molecular docking. Key pharmacophores were identified among the structure-similar compounds. Our studies suggest that different functional groups are highly correlated with the efficacy for inhibiting p7 of HCV, in which hydrophobic interactions are the dominant forces for the inhibition potency. Our findings provide guiding principles for designing higher affinity inhibitors of p7 as potential anti-HCV drug candidates.

Simultaneous determination of insecticide fipronil and its metabolites in maize and soil by gas chromatography with electron capture detection.

An integrated method for the simultaneous determination of insecticide fipronil and its three metabolites, desulfinyl, sulfide, and sulfone, in maize grain, maize stem, and soil was developed. This three-step method uses liquid-solid extraction with ultrasound or mechanical grinding, followed by liquid-liquid partitioning and florisil solid-phase extraction (SPE) for cleanup. The quantification was conducted by gas chromatography-electron capture detection in triplicate for each sample. The method was validated with five replicates at three fortification concentrations, 0.002, 0.01, and 0.1 mg kg(-1), in each matrix and gave mean recoveries from 83 to 106 % with relative standard deviation ≤ 8.9 %. The limits of quantification (LOQ) were 0.002 mg kg(-1) for the compounds in all matrixes. In the field study in Beijing and Shandong 2012, fipronil-coated maize seeds were planted and the proposed method was applied for checking the possible existence of four compounds in maize and soil samples, but none of them contained residues higher than the LOQs in both application rates. Moreover, the dissipation of fipronil in soil fits first-order kinetics with half-lives 9.90 and 10.34 days in Beijing and Shandong, respectively. Combined with an adequate sample treatment, this technique offers good sensitivity and selectivity in the three complex matrixes. The results could provide guidance for the further research on pesticide distribution and safe use of fipronil as seed coat in cereals.