Objective:To investigate the effect of different programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1) inhibitors combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC).Methods:All randomized controlled trials (RCT) of PD-1/PD-L1 inhibitors for the first-line treatment of ES-SCLC from the establishment of the database to March 2025 were searched in CNKI database, Wanfang database, VIP Chinese Science and Technology Journal database, China Biomedical Literature Service System, PubMed database, Cochrane Library database and Embase database. Literatures were screened according to inclusion and exclusion criteria, and data were extracted. A network meta-analysis was performed using R 4.3.1 software to analyze the survival and safety of patients with ES-SCLC treated with PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy±placebo first-line treatment.Results:A total of 8 RCT involving 3 832 patients with ES-SCLC were included in this analysis. PD-1/PD-L1 inhibitors included pembrolizumab, serplulimab, toripalimab, tislelizumab, adebrelimab, durvalumab, atezolizumab and benmelstobart, and benmelstobart combined with anti-vascular targeted drug anlotinib; the chemotherapy regimen was etoposide combined with platinum-based drugs. Except for durvalumab combined with chemotherapy compared with chemotherapy alone, the control group of the rest was chemotherapy combined with placebo. The included study data were complete and the risk of bias was small, and there was no closed loop in the outcome measures, so the consistency model was uniformly used for analysis. The results of network meta-analysis showed that compared with the control group, PD-1/PD-L1 inhibitors combined with chemotherapy benefited the progression-free survival (PFS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in PFS ( HR = 0.32, 95% CI: 0.25-0.40, P < 0.05), and this regimen could benefit the PFS of patients more than other PD-1/PD-L1 inhibitors combined with chemotherapy and serplulimab combined with chemotherapy could benefit the PFS of patients more than pembrolizumab, toripalimab, adebrelimab, durvalumab, and atezolizumab combined with chemotherapy (all P < 0.05). The results of network meta-analysis showed that compared with the control group, all PD-1/PD-L1 inhibitors combined with chemotherapy benefited the overall survival (OS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in OS ( HR = 0.61, 95% CI: 0.47-0.79, P < 0.05), but there was no statistically significant difference in OS benefit between each PD-1/PD-L1 inhibitor combined with chemotherapy (all P > 0.05). Ranking of the efficacy of all interventions, the P-scores for PFS and OS were the highest for benmelstobart and anlotinib combined with chemotherapy, which were 0.99 and 0.89, respectively. The results of the network meta-analysis showed that, except for the higher risk of ≥ grade 3 adverse reactions in benmelstobart and anlotinib combined with chemotherapy group compared to the control group ( OR = 2.01, 95% CI: 1.09-3.73, P < 0.05), there was no statistically significant difference in the risk of ≥ grade 3 adverse reactions between the other PD-1/PD-L1 inhibitors combined with chemotherapy group and the control group, or between all PD-1/PD-L1 inhibitors combined with chemotherapy groups (all P > 0.05). Among all PD-1/PD-L1 inhibitors combined with chemotherapy regimens, the tislelizumab combined with chemotherapy regimen had the lowest incidence of ≥grade 3 adverse reactions, with a P-score of 0.70. Conclusions:For the first-line treatment of ES-SCLC patients, the combination of PD-1/PD-L1 inhibitors and chemotherapy regimen has better survival benefits than chemotherapy regimen. Among them, compared with other PD-1/PD-L1 inhibitors, benmelstobart and anlotinib may benefit patients' survival more, but its related adverse reactions should be noted.

Objective:To investigate the effect of different programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1) inhibitors combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC).Methods:All randomized controlled trials (RCT) of PD-1/PD-L1 inhibitors for the first-line treatment of ES-SCLC from the establishment of the database to March 2025 were searched in CNKI database, Wanfang database, VIP Chinese Science and Technology Journal database, China Biomedical Literature Service System, PubMed database, Cochrane Library database and Embase database. Literatures were screened according to inclusion and exclusion criteria, and data were extracted. A network meta-analysis was performed using R 4.3.1 software to analyze the survival and safety of patients with ES-SCLC treated with PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy±placebo first-line treatment.Results:A total of 8 RCT involving 3 832 patients with ES-SCLC were included in this analysis. PD-1/PD-L1 inhibitors included pembrolizumab, serplulimab, toripalimab, tislelizumab, adebrelimab, durvalumab, atezolizumab and benmelstobart, and benmelstobart combined with anti-vascular targeted drug anlotinib; the chemotherapy regimen was etoposide combined with platinum-based drugs. Except for durvalumab combined with chemotherapy compared with chemotherapy alone, the control group of the rest was chemotherapy combined with placebo. The included study data were complete and the risk of bias was small, and there was no closed loop in the outcome measures, so the consistency model was uniformly used for analysis. The results of network meta-analysis showed that compared with the control group, PD-1/PD-L1 inhibitors combined with chemotherapy benefited the progression-free survival (PFS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in PFS ( HR = 0.32, 95% CI: 0.25-0.40, P < 0.05), and this regimen could benefit the PFS of patients more than other PD-1/PD-L1 inhibitors combined with chemotherapy and serplulimab combined with chemotherapy could benefit the PFS of patients more than pembrolizumab, toripalimab, adebrelimab, durvalumab, and atezolizumab combined with chemotherapy (all P < 0.05). The results of network meta-analysis showed that compared with the control group, all PD-1/PD-L1 inhibitors combined with chemotherapy benefited the overall survival (OS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in OS ( HR = 0.61, 95% CI: 0.47-0.79, P < 0.05), but there was no statistically significant difference in OS benefit between each PD-1/PD-L1 inhibitor combined with chemotherapy (all P > 0.05). Ranking of the efficacy of all interventions, the P-scores for PFS and OS were the highest for benmelstobart and anlotinib combined with chemotherapy, which were 0.99 and 0.89, respectively. The results of the network meta-analysis showed that, except for the higher risk of ≥ grade 3 adverse reactions in benmelstobart and anlotinib combined with chemotherapy group compared to the control group ( OR = 2.01, 95% CI: 1.09-3.73, P < 0.05), there was no statistically significant difference in the risk of ≥ grade 3 adverse reactions between the other PD-1/PD-L1 inhibitors combined with chemotherapy group and the control group, or between all PD-1/PD-L1 inhibitors combined with chemotherapy groups (all P > 0.05). Among all PD-1/PD-L1 inhibitors combined with chemotherapy regimens, the tislelizumab combined with chemotherapy regimen had the lowest incidence of ≥grade 3 adverse reactions, with a P-score of 0.70. Conclusions:For the first-line treatment of ES-SCLC patients, the combination of PD-1/PD-L1 inhibitors and chemotherapy regimen has better survival benefits than chemotherapy regimen. Among them, compared with other PD-1/PD-L1 inhibitors, benmelstobart and anlotinib may benefit patients' survival more, but its related adverse reactions should be noted.

Objective To analyze the effect of fisetin against venous thrombosis in rats.Methods Seventy SD rats were randomly divided into the following groups:sham-operation group,model group,fisetin 45 mg/kg,15 mg/kg,5 mg/kg groups,and aspirin group(47 mg/kg).The corresponding medication was administered by gavage once a day consecutively(the sham-operation group and the model group were given 0.5％carboxymethyl cellulose sodium solution with 10 mL/kg,respectively)for 7 consecutive days.One hour after the last administration,the rats were anesthetized,the lower part of the intersection of inferior vena cava and left renal vein was ligated with silk thread(no ligation in the sham-operation group),and the abdominal wall was sutured.Two hours later,the abdominal cavity was reopened,the other venous branches 1.5 cm away from the ligation site were closed with the artery clamp,and blood was collected from the abdominal aorta.The anticoagulant ratio of 3.8％sodium citrate∶whole blood was 1∶9.The venous thrombus 1 cm down from the ligation point of the intersection of inferior vena cava and left renal vein was cut and the thrombus was separated.The residual blood was dried with filter paper,weighed and recorded.Plasma was taken after anticoagulant blood centrifugation.The levels of plasma antithrombin-Ⅲ(AT-Ⅲ),protease C(PC),plasminogen(PLG),and plasminogen activator inhibitor(PAI-1)were detected by ELISA kits.Results Compared with the model group,the weight of thrombus in fisetin 45 mg/kg group and aspirin 47 mg/kg group decreased(P＜0.01).The content of AT-Ⅲ in three fisetin groups increased(all P＜0.05).The content of PC in fisetin 45 mg/kg increased(P＜0.05).The content of PLG and PAI-1 in fisetin 45 mg/kg group decreased(both P＜0.05).Conclusion Fisetin has the effect against venous thrombosis in vivo,and the effect is related to the upregulation of AT-Ⅲ and PC and the downregulation of PLG and PAI-1.

OBJECTIVE To evaluate the cost-effectiveness of tislelizumab monotherapy in the second-line treatment of advanced or metastatic esophageal squamous cell carcinoma （ESCC），so as to provide reference for rational use of drug in clinic. METHODS A three-state partitioned survival model was constructed from the perspective of China’s health system， based on the data of RATIONALE-302 study，with simulation time limit of 10 years， cycle period of 1 month. The incremental cost-effectiveness ratio （ICER） was calculated with quality-adjusted life year （QALY） as utility index. The cost-effectiveness of tislelizumab monotherapy was compared with that of chemotherapy for second-line treatment of advanced or metastatic ESCC by cost-utility analysis. The stability of basic analysis results was validated through sensitivity analysis and scenario analysis. RESULTS The results of basic analysis showed that compared with chemotherapy group， incremental cost per capita of tislelizumab group was 35 025.32 yuan，and incremental utility per capita was 2.71 QALYs； ICER was 12 892.31 yuan/QALY， which was far lower than the willingness-to-pay （WTP） threshold of 3 times of China’s per capita gross domestic product （GDP） 242 928 yuan in 2021. The results of univariate sensitivity analysis showed that parameters such as the cost of apatinib， the utility value of disease progression status and the cost of adverse reactions in the chemotherapy group had a great impact on the ICER value， but these parameters could not cause the reversal of the basic analysis results. Probabilistic sensitivity analysis showed that WTP threshold was higher than 80 000 yuan/QALY，the probability of tislelizumab monotherapy possessed cost-effectiveness was 100%. Results of scenario analysis showed that in which model simulation time lasted for 5 or 20 years，ICER of tislelizumab was 8 331.00 yuan/QALY and 12 981.00 yuan/QALY， which were less than 3 times of China’s per capita GDP in 2021 as WTP threshold. CONCLUSIONS When three times of China’s GDP per capita in 2021 is taken as the WTP threshold， the second-line treatment of tirelizumab monotherapy for advanced or metastatic ESCC is more cost-effective than chemotherapy.