Objective:To investigate the changes of circulating tumor DNA (ctDNA), circulating B cell-specific Moloney leukemia virus insertion site 1 mRNA (Bmi-1 mRNA) and microRNA-21 (miR-21) before and after treatment with epidermal growth factor receptor (EGFR) monoclonal antibody in advanced colorectal cancer, and analyze their association with treatment response.Methods:The clinical data of 98 patients with advanced colorectal cancer from March 2019 to March 2021 in Yantai Yuhuangding Hospital were retrospectively analyzed. After treatment with cetuximab, complete remission was in 4 cases, partial remission in 26 cases, stable disease in 39 cases, and progressive disease in 29 cases. The patients with complete remission and partial remission were classified as remission group (30 cases), the stable disease and progressive disease were classified as non-remission group (68 cases). Before treatment and after 2 cycles of treatment, the plasma level of ctDNA was detected by high-throughput sequencing; the levels of Bmi-1mRNA and miR-21 were detected by real-time fluorescence quantitative polymerase chain reaction. Spearman correlation was used to analyze the relationship between ctDNA, Bmi-1mRNA, miR-21 and treatment responsiveness after 2 cycles of treatment; multivariate Logistic regression was used to analyze the independent risk factors affecting treatment responsiveness; receiver operating characteristic (ROC) curve was drawn to evaluate the value of ctDNA, Bmi-1mRNA and miR-21 in predicting remission after 2 cycles of treatment.Results:There were no significant differences in ctDNA, Bmi-1mRNA and miR-21 before treatment between 2 groups ( P>0.05); the ctDNA, Bmi-1mRNA and miR-21 after 2 cycles of treatment in remission group were significantly lower than those in non-remission group: (10.03 ± 3.32) μg/L vs. (15.33 ± 5.14) μg/L, 0.13 ± 0.04 vs. 0.19 ± 0.05 and 0.81 ± 0.26 vs. 1.08 ± 0.24, and there were statistical differences ( P<0.01). Spearman correlation analysis result showed that ctDNA, Bmi-1mRNA and miR-21 were negatively correlated with treatment response ( r = -0.500, -0.506 and -0.531; P<0.01). Multivariate Logistic regression analysis result showed that, after controlling for the number of distant metastatic organs and clinical stage, ctDNA, Bmi-1mRNA and miR-21 were still independent risk factors for treatment response in patients with advanced colorectal cancer ( OR = 3.342, 2.725 and 1.838; 95% CI 3.116 to 3.584, 2.647 to 2.805 and 1.768 to 1.911; P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of ctDNA, Bmi-1mRNA combined with miR-21 after 2 cycles of treatment to predict the treatment response was the largest with 0.922. Conclusions:The changes of ctDNA, Bmi-1mRNA and miR-21 in patients with advanced colorectal cancer before and after treatment with EGFR monoclonal antibody are related to the treatment response. Combined detection is helpful for screening patients sensitive to EGFR-targeted therapy, and can provide reference for new targets of molecular intervention.

Objective:To investigate the role of concurrent chemoradiotherapy in the treatment of limited-stage small cell lung cancer (LS-SCLC) and the impact of the number of chemotherapy cycle during radiotherapy (RT) on clinical prognosis.Methods:Patients with LS-SCLC treated with definitive radiotherapy from May, 2008 to September, 2016 were included in the study. The primary endpoint was overall survival (OS), which was calculated from the start of treatment to the date of death or last follow-up. The effect of the number of concurrent chemotherapy cycle and other clinical factors on clinical efficacy was analyzed. Survival analysis was performed with Kaplan- Meier method, and multivariate analysis was performed with Cox regression model. Results:Three hundred and seventeen patients were eligible for the analysis. Among them, 129 patients received sequential chemoradiotherapy and 188 patients received concurrent chemoradiotherapy. Among patients receiving concurrent chemoradiotherapy, 86 patients received 1 cycle of concurrent chemotherapy and 102 cases of 2 cycles of concurrent chemotherapy. The median follow-up time was 22.47 months. Multivariate survival analysis showed that only clinical stage, timing of RT administration and prophylactic cranial irradiation (PCI) were the independent prognostic factor for OS. The median OS in patients who received 1 cycle and 2 cycles of concurrent chemotherapy during RT were 33.8 months and 30.4 months ( P=0.400). No matter in elder patients or in younger patients, in early RT group or in late RT group and application of PCI or not, the number of concurrent chemotherapy cycle exerted no significant impact on OS. The incidence of grade 3 or above adverse events was 20% in the 1-cycle concurrent chemotherapy group, and 13.7% in the 2-cycle concurrent chemotherapy group. Conclusions:Concurrent chemoradiotherapy is the standard treatment of LS-SCLC. Two cycles of concurrent chemotherapy during RT is not necessarily superior to 1 cycle of concurrent chemotherapy. The optimal number of concurrent chemotherapy cycle during RT need to be studied in a large prospective randomized clinical trial.

Objective: To explore the relationships of neutrophil gelatinase-associated lipocalin (NGAL) with severity of skin lesions in children with psoriasis and peripheral neutrophil count, and to evaluate in vitro effect of NGAL on expression of tumor necrosis factor-α (TNF-α) and interleukin-22 (IL-22) by a human immortalized keratinocyte cell line HaCaT. Methods: From January 1st 2017 to December 31st 2018, 98 children who newly developed psoriasis were enrolled from Department of Dermatology of 6 hospitals in China, including 51 males and 47 females. Their age was 7.00 ± 2.99 years (range: 3-14 years) , and their course of disease was 7.4 ± 5.85 days (range: 3-28 days) . The serum level of NGAL was detected in all the patients before and two weeks after treatment, and the relationships of NGAL with psoriasis area and severity index (PASI) scores and peripheral neutrophil count were evaluated. Western blot analysis and reverse-transcription (RT) -PCR were performed to determine the protein and mRNA expression of TNF-α and IL-22 in HaCaT cells, respectively, after 12-hour treatment with NGAL at concentrations of 0 (control group) , 0.125, 0.25, 0.5, 1 mg/L. Statistical analysis was carried out with SPSS 16 software. by using t test and one-way analysis of variance. Results: After 2-week treatment, the PASI score, neutrophil count and NGAL level in children with psoriasis significantly decreased (1.80 ± 1.19, [6.16 ± 0.76] × 10⁹/L, 90.86 ± 0.75 μg/L, respectively) compared with those before the treatment (10.38 ± 3.42, [11.01 ± 2.85] × 10⁹/L, 113.48 ± 21.26 μg/L, respectively; t = 31.42, 18.34, 16.37 respectively, all P < 0.001) . Before the treatment, the serum level of NGAL in the patients was positively correlated with the PASI score and peripheral neutrophil count (r = 0.918, 0.799 respectively, both P < 0.05) . The mRNA and protein expression of IL-22 in HaCaT cells significantly differed among these groups treated with different concentrations of NGAL (F = 176.31, 296.96 respectively, both P < 0.001) , so did the mRNA and protein expression of TNF-α (F = 193.28, 318.80 respectively, both P < 0.001) . Additionally, the protein and mRNA expression of IL-22 and TNF-α in HaCaT cells was significantly higher in the 0.125-, 0.25-, 0.5- and 1-mg/L NGAL group than in the control group (all P < 0.05) . The NGAL level was positively correlated with the protein and mRNA expression of TNF-α and IL-22 in HaCaT cells (all P < 0.05) . Conclusions The serum level of NGAL was high in children with psoriasis, and positively correlated with severity of skin lesions and peripheral neutrophil count. NGAL can upregulate the expression of TNF-α and IL-22 in HaCaT cells in vitro.