Objective: This study was designed to evaluate the clinical value of seven combinedtumor-associated autoantibodies (7-TAAB) in the diagnosis of non-small cell lung cancer (NSCLC). Methods: This is a cross-sectional study. The 81 newly diagnosed patients with NSCLC were enrolled. 46 patients with benign pulmonary diseases (BLD) and 55 healthy subjects were selected as the BLD group and the healthy control (HC) group, respectively. ELISA was used to detect the concentration of seven TAABs of p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE A1 and CAGE in the serum of the NSCLC and the other two groups. The levels of lung cancer tumor markers CEA, NSE, SCC and CYFRA21-1 in serum were also detected in all enrolled subjects. Kruskal-wallis test was used for comparison among the three groups, Mann-Whitney test was used to evaluate the differences between the two groups, and positivity rates were analyzed by using standard χ² tests and Fisher exact tests. The receiver operating characteristic (ROC) analyses were performed to evaluate the diagnostic efficacy of 7-TAAB or combination of 7-TAAB and traditional tumor markers. Results: The serological levels of six TAABs (p53, SOX2, GAGE7, GBU4-5, MAGE A1, and CAGE) in the NSCLC group were higher than that in the BLD group (p53: Z=-4.370, P=0.000; SOX2: Z=-4.412, P=0.000; GAGE7: Z=-4.250, P=0.001; GBU4-5: Z=-2.678, P=0.025; MAGE A1: Z=-4.504, P=0.002; CAGE: Z=-4.646, P=0.001) and the HC group (p53: Z=-3.543, P=0.000; SOX2: Z=-3.383, P=0.002; GAGE7: Z=-4.893, P=0.001; GBU4-5: Z=-3.381, P=0.025; MAGE A1: Z=-3.369, P=0.001; CAGE: Z=-2.981, P=0.002),respectively. The differences were statistically significant. The comparison of PGP9.5 in NSCLC group with that in the BLD group was statistically significant (Z=-2.871, P=0.044), with that in the HC group was no difference (Z=-2.280, P=0.05). None of the seven TAABs showed a significant difference between the BLD group and the HC group (p53: Z=-1.917, P=0.917; PGP9.5: Z=-1.228, P=0.966; SOX2: Z=-1.789, P=0.325; GAGE7: Z=-0.563, P=1.000; GBU4-5: Z=-0.315, P=0.985; MAGE A1: Z=-2.310, P=0.857; CAGE: Z=-2.822, P=0.703). According to the criteria of cut-off value, the detection value of individual TAAB was judged as negative or positive. The specificity of every single TAAB to NSCLC was ≥89%, but the sensitivity was ≤39.5%. Positive in any of the single TAAB was considered as a positive result of 7-TAAB, the positive rate of 7-TAAB in NSCLC subgroups with early stages (stageⅠand stageⅡ) was considered higher than that of traditional biomarkers (7-TAAB:52.94%, CEA: 23.53%, NSE: 8.82%, CYFRA21-1∶20.59%, SCC:14.71%), and 7-TAAB was more sensitive to NSCLC patients with poor prognosis, such as advanced stages (stageⅢand stageⅣ) and moderately-poorly differentiation. The AUC of 7-TAAB was 0.734, with a sensitivity of 66.67% and a specificity of 80.20%. In coordination with 7-TAAB, CEA, NSE, CYFRA21-1 and SCC, the AUC was 0.917, with a sensitivity of 87.70% and a specificity of 81.20%. Conclusions 7-TAAB, regarded as a panel of serological markers, is helpful in NSCLC diagnosis and shows broad application prospect. The detection rate of 7-TAAB in patients with early NSCLC is superior to that of traditional serum tumor markers, and the combination of 7-TAAB with CEA, NSE CYFRA21-1 and SCC could improve the diagnosis sensitivity of patients with NSCLC.

To locate the nuclei in hematoxylin-eosin (HE) stained section images more simply, efficiently and accurately, a new method based on distance estimation is proposed in this paper, which shows a new mind on locating the nuclei from a clump image. Different from the mainstream methods, proposed method avoids the operations of searching the combined singles. It can directly locate the nuclei in a full image. Furthermore, when the distance estimation built on the matrix sequence of distance rough estimating (MSDRE) is combined with the fact that a center of a convex region must have the farthest distance to the boundary, it can fix the positions of nuclei quickly and precisely. In addition, a high accuracy and efficiency are achieved by this method in experiments, with the precision of 95.26% and efficiency of 1.54 second per thousand nuclei, which are better than the mainstream methods in recognizing nucleus clump samples. Proposed method increases the efficiency of nuclear location while maintaining the location's accuracy. This can be helpful for the automatic analysis system of HE images by improving the real-time performance and promoting the application of related researches.

Objective To explore the association of serum cytokine levels with disease activity in patients with dermatomyositis (DM) and clinically amyopathic dermatomyositis (CADM),especially their association with skin lesions and interstitial lung disease (ILD).Methods Enzyme-linked immunosorbent assay (ELISA) and cytometric beads array (CBA)were performed to detect the serum levels of interleukin (IL)-2,IL-4,IL-6,IL-10,IL-17A,IL-18,tumor necrosis factor (TNF) and interferon (IFN)-γin 40 patients with DM or CADM,as well as in 16 health checkup examinees (healthy control group).Then,the association of serum cytokine levels with skin lesions,inflammatory biomarkers and severity of ILD was analyzed.Results The patients with DM/CADM showed significantly higher serum levels of IL-6 (37.8 ±45.8 pg/ml),IL-10 (16.1 ± 7.2 pg/ml) and IL-18 (492.0 ± 193.1 pg/ml) compared with the healthy controls (12.0 ± 2.7 pg/ml,7.7 ± 1.4 pg/ml,191.1 ± 39.2 pg/ml,respectively,all P ＜ 0.001),and there were no significant differences in the serum levels of the other 5 cytokines between the above 2 groups.The serum level of IL-6 was significantly higher in patients with elevated erythrocyte sedimentation rate (ESR) than in those with normal ESR (49.7 ± 46.8 pg/ml vs.29.1 ± 45.4 pg/ml,P =0.008).The patients with raised C-reactive protein (CRP) levels showed significantly higher serum levels of IL-6 (68.7 ± 59.7 pg/ml) and IL-18 (635.1 ± 232.8 pg/ml) compared with those with normal CRP levels (IL-6:30.6 ± 40.3 pg/ml,P =0.013;IL-18:440.2 ± 164.7 pg/ml,P =0.020).Moreover,the patients with elevated levels of lactate dehydrogenase (LDH) showed significantly higher serum levels of IL-10 (18.4 ± 6.9 pg/ml),IL-17A (19.6 ±6.7 pg/ml) and IL-18 (529.4 ± 197.2 pg/ml) compared with those with normal LDH levels (IL-10:10.7 ±4.8 pg/ml,P ＜ 0.001;IL-17A:11.4 ± 6.6 pg/ml,P =0.001;IL-18:404.9 ± 158.0 pg/ml,P =0.037).No significant difference in the cytokine levels was observed between the patients with elevated creatine kinase (CK) levels and those with normal CK levels.The patients with Gottron's papules/sign showed significantly higher serum levels of IL-18 (513.7 ± 187.2 pg/ml) compared with those without Gottron's papules/sign (297.1 ± 140.4 pg/ml,P ＜ 0.05).The serum levels of IL-10 and IL-18 were significantly higher in the patients with DM/CADM complicated by ILD (18.0 ± 6.7 pg/ml,552.3 ± 192.8 pg/ml,respectively) than in those without ILD (11.6 ± 6.5 pg/ml,351.4 ± 101.0 pg/ml,respectively,both P =0.001).Conclusion Serum levels of IL-6,IL-10 and IL-18 are highly associated with inflammatory biomarkers,skin lesions and ILD in patients with DM/CADM.