Objective To investigate the clinical efficacy and safety of the combination therapy of multi-targeted small molecule tyrosine kinase inhibitors(MTKIs)with immune checkpoint inhibitors(ICIs)for late-stage solid tumor in the patients with failed standard treatment regimens.Methods The patients with advanced solid tumors who had been hospitalized in our hospital from January 2021 to January 2023 after failure of≥2 standard treatment regimens were selected and treated with MTKIs combined with ICIs.The efficacy and safety of this regimen were retrospectively studied.Results A total of 21 patients were included.As of March 1,2022,the overall popula-tion had an ORR of 38%,a DCR of 67%,a median progression free survival(mPFS)of 10 months,and a median survival(mOS)of 15 months.Common adverse reactions were pneumonia and oral ulcers.Conclusion For the patients with advanced solid tumors who have failed standard treatment,MTKIs combined with ICIs may be a treat-ment option,but prospective studies with a larger sample size are needed to confirm the efficacy and safety of this combination therapy and to explore the population most likely to benefit from this treatment method.

Objective To investigate the clinical value of the ratio of plasma vascular endothelial growth factor level to platelet count (VEGF/PLT) in predicting 28-day prognosis in patients with sepsis.Methods A prospective cohort study was conducted.From September 2009 to March 2013,164 sepsis patients in Intensive Care Unit (ICU) of Guangdong General Hospital were included for study.Patients with age younger than 18 years old,the illness already reaching final stage of chronic diseases,suffering from two or more organs dysfunction within 3 days,acute pancreatitis without infection,or less than 28 days of expected survival time were excluded.Finally,135 patients were included in the further analysis.Peripheral blood samples were collected at admission.Routine blood tests were done,and then VEGF levels in plasma were measured by enzyme linked immunosorbent assay (ELISA).Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores were recorded every day for 7 days.Patients' prognosis was assessed during the following 28 days.The patients were divided into 28-day survival group and non-survival group.Comparison between two groups was done by single factor analysis.Spearman rank correlation was used to analyze the correlation between VEGF levels and PLT.Mutivariate logistic regression analysis was performed to identify the independent risk factor for 28-day prognosis.Receiver operating characteristic curve (ROC curve) was plotted,and the effect of related indexes on predicting 28-day survival was evaluated by area under ROC curve (AUC).Results There were no significant differences in VEGF (ng/L:471.73 ± 198.34 vs.383.49 ± 266.54,t=-1.918,P=0.057),PLT (× 109/L:220.40±127.60 vs.246.42± 100.72,t=1.275,P=0.204),leucocyte counts (× 109/L:12.48 ±4.62 vs.13.70 ±5.97,t=1.063,P=0.292),mean arterial pressure [mmHg (1 mmHg=0.133 kPa):86.50 ± 12.04 vs.91.03 t 13.10,t=1.557,P=0.123] and blood lactic acid (mmol/L:1.79 ± 1.30 vs.1.50 ± 0.60,t=-1.768,P=0.079) at admission between the non-survival group (n=42) and survival group (n=93).VEGF/PLT (2.59 ± 1.44 vs.1.73 ± 1.13,t=-3.756,P=0.000) as well as APACHE Ⅱ scores (15.50 ± 4.50 vs.13.28 ± 4.61,t =-2.022,P=0.045) of the non-survival group were significantly higher than those of survival group,and oxygenation index (PaO2/FiO2) of the non-survival group was significantly lower than that of survival group (kPa:32.38 ± 11.12 vs.37.04 ± 10.97,t=2.278,P=0.024).Correlation analysis showed that the concentration of VEGF was positively correlated with PLT (r=0.271,P=0.001).It was shown by multivariate logistic regression analysis that only VEGF/PLT was the independent risk factor in predicting 28-day prognosis in patients with sepsis [odds ratio (OR) was 1.591,95％ confidence interval (95％CI) 1.164-2.175,P=0.004].AUC of VEGF/PLT was 0.704 ± 0.047 (P=0.000,95％CI:0.611-0.797) for predicting 28-day survival.The optimal cut-off point was 1.32,and the sensitivity and specificity were 81.0％ and 48.4％,respectively.Conclusion VEGF/PLT can be used as one of the indicators to predict 28-day survival in patients with sepsis.