BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective:To investigate changes in the expression of Cosmc and T-synthase in peripheral B lymphocytes and in serum levels of galactose-deficient IgA1 (Gd-IgA1) in patients with Henoch-Sch?nlein purpura (HSP) .Methods:From January to August 2014, 56 patients with HSP were collected from outpatient or inpatient department of dermatology and venereology in the Second Hospital of Hebei Medical University, and were divided into 4 groups, including skin type group (22 cases) , joint type group (9 cases) , abdominal type group (12 cases) and renal type group (13 cases) . Twenty healthy volunteers served as healthy controls. Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of Cosmc and T-synthase in peripheral B lymphocytes, and a lectin-based enzyme-linked immunosorbent assay (ELISA) to detect the serum level of Gd-IgA1. Comparisons among multiple groups were performed using one-way analysis of variance or Kruskal-Wallis H test, multiple comparisons were performed using least significant difference (LSD) - t test or Nemenyi test, and correlation analysis was performed using Spearman rank correlation analysis. Results:There was a significant difference in the duration from disease onset to the clinic visit ( χ2= 26.19, P < 0.05) among the skin type group (6.27 ± 3.09 d) , joint type group (5.56 ± 3.05 d) , abdominal type group (6.75 ± 3.75 d) , and renal type group (26.23 ± 14.12 d) , and the duration from disease onset to the clinic visit was significantly longer in the renal type group than in the other 3 groups (all P < 0.05) . The Cosmc mRNA expression significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group (0.849 ± 0.239, 0.767 ± 0.181, 0.719 ± 0.183, 0.459 ± 0.121, 1.146 ± 0.232, F= 23.37, P < 0.05) , was significantly lower in the 4 patient groups than in the healthy control group ( P < 0.01) , and lower in the renal type group than in the other 3 patient groups (all P < 0.01) . There was no significant difference in the T-synthase mRNA expression in peripheral B lymphocytes among the patient groups and healthy control group ( F= 1.05, P > 0.05) . The serum level of Gd-IgA1 significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group ( F= 7.06, P < 0.05) . Moreover, the Gd-IgA1 level was significantly higher in the patient groups than in the healthy control group (all P < 0.05) , and higher in the renal type group than in the other 3 patient groups (all P < 0.05) . The serum level of Gd-IgA1 in the HSP patients was significantly and negatively correlated with the mRNA expression of Cosmc ( rs=-0.50, P < 0.01) . Conclusion:Decreased mRNA expression of Cosmc and increased serum levels of Gd-IgA1 were observed in patients with HSP, and there was a negative correlation between the two indices.

Gefitinib (iressa),an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor,has antitumor activity in non-small-cell lung cancer (NSCLC).Despite the dramatic response to this inhibitor,most patients nevertheless ultimately have relapses because of the secondary resistance.In human lung adenocar-cinomas with EGFR mutation,a second-site point mutation that substitutes methionine for threonine at position 790(T790M) is associated with approximately half of cases of secondary resistance to gefitinib.Other mecha-nisras that contribute to gefitinib resistance include EGFR receptor internalization and MET gene amplification.

AIM: To observe the changes of endogenous hydrogen sulfide/cystathionine-?-lyase(H2S/CSE) system while acute lung injury induced by LPS in rats.METHODS: Eighty rats were randomly divided into six groups(n=8): Ⅰ,control group;Ⅱ,LPS 1 h group;Ⅲ,LPS 3 h group;Ⅳ,LPS 6 h group;Ⅴ,LPS 9 h group;Ⅵ,LPS 12 h group.The ALI model of rats was prepared with LPS.The rats were respectively killed at 1,3,6,9 or 12 h after administration of LPS.The morphological changes of lung tissues were observed by light and electron microscope.The lung coefficient and the wet-to-dry weight ratio were measured.The contents of IL-1? and IL-10 in serum,the H2S level in plasma and the CSE activity in lung tissue were respectively detected.RESULTS: ⑴ In LPS 1 h group,the morphology,the lung coefficient,the wet-to-dry weight ratio,the H2S level and the CSE activity showed no changes compared with the control group.The contents of IL-1? and IL-10 were increased compared with the control group(IL-1?,P