[Abstract] Objective: To systematically evaluate the efficacy and safety of nivolumab plus ipilimumab versus nivolumab monotherapy in the treatment of malignant tumors, so as to provide evidence-based medical proof for clinical administration. Methods: Databases, such as PubMed, CNKI, VIP, and Wanfang Data, were searched from January 2000 to January 2022 to collect the clinical trial data in terms of nivolumab plus ipilimumab versus nivolumab monotherapy for malignant tumors were published in both domestic and abroad. Two reviewers independently evaluated the quality of included RCTs, and extracted and cross-checked the data. RevMan 5. 4 was used for the Meta-analysis. Results: A total of 7 RCTs studies including 10 articles were included. Compared with the nivolumab monotherapy group, the OS of patients in the combined treatment group was significantly improved (HR=0.86, 95% CI:0. 75-0.99, P=0. 03), and the PFS was significantly prolonged (HR=0.69, 95% CI: 0.55-0.85, P=0.000 6). However, as for safety, treatment-related adverse events (OR=3.18, 95% CI: 1.55-6.55, P=0.002) and adverse events leading to drug discontinuation (OR=7.11, 95% CI: 4.85-10.42, P<0.000 01) in the combination therapy group were significantly higher than those in the monotherapy group. Conclusion: Compared with nivolumab monotherapy, nivolumab plus ipilimumab can significantly improve the OS and PFS of tumor patients, but is also associated with more treatment-related adverse events and adverse events leading to drug discontinuation. Therefore, it is necessary to pay attention to follow-up and regular monitoring to prevent the occurrence of serious adverse reactions.

ABSTRACT OBJECTIVE：To study the effects of the extract of Xiongmatang on 5-HT and CGRP in brain tissue of rats with liver-yang hyperactivity and blood stagnation migraine. METHODS：Fifty male spontaneously hypertension （SHR） rats were randomly divided into model control group，Zhengtian pill positive control group （1.6 g/kg），the extract of Xiongmatang low-dose，medium-dose and high-dose groups（4.5，9.0，18.0 g/kg，by crude drug），with 10 rats in each group. Another 10 normal rats were taken as normal control group. Administration group was given relevant medicine intragastrically，once a day，for consecutive 28 d. Normal control group and model control group were given equal volume normal saline intragastrically. After last administration，except for normal control group，other groups were used to stimulate trigeminal ganglia（10 min）to establish liver-yang hyperactivity and blood stagnation migraine model，and maintained the administration once more after making the model. 30 min later，general behavior and tongue quality of rats were observed，and the blood pressure was measured；the contents of 5-HT and CGRP in cerebral tissue of rats were determined by ELISA. The protein expression of CGRP in cerebral tissue of rats were determined by Western blot method. RESULTS： Compared with the normal control group， the rats in the model control group had behavioral symptoms，such as the color of conjunctiva deepened and reddened， excessive hairdressing，head flicking，and most of the rats had purple tongue；the systolic pressure and the content and protein expression of CGRP were all increased obviously（P＜0.05 or P＜0.01）， while the content of 5-HT in cerebral tissue was decreased obviously（P＜0.01）. Compared with model control group，general behavior and tongue quality of rats were improved significantly in administration groups. Systolic pressure，the content and the protein expression of CGRP in cerebral tissue of rats were decreased significantly in Zhengtian pill positive control group and the extract of Xiongmatang high-dose group （P＜0.05），while the content of 5-HT in cerebral tissue of rats were increased significantly in Zhengtian pill positive control group，the extract of Xiongmatang medium-dose and high-dose groups（P＜0.05）.CONCLUSIONS：The extract of Xiongmatang has obvious protective effect on liver-yang hyperactivity and blood stagnation migraine model rats，the mechanism of which may be associated with reducing the content of CGRP in cerebral tissue and raising the content of 5-HT in cerebral tissue