Objective To systematically evaluate the efficacy and safety of different administration methods of recombinant human endostatin(Endostatin)in the treatment of malignant pleural effusion in non-small cell lung cancer(NSCLC),and to provide more evidence-based bases for the clinical standardization of the use of Endostatin beyond the drug specification.Methods PubMed,The Cochrane Library,Web of Science,Embase,ChiCTR,VIP,CNKI,WanFang,and SinoMed databases were searched by computer for randomized controlled trials(RCT)of Endostatin alone or combined with chemotherapy for malignant pleural effusion in NSCLC.Network Meta-analysis was performed using Stata 14.0 software.Results A total of 50 RCTs involving 3 429 patients were included,covering 5 intervention measures.Network Meta-analysis showed that in terms of clinical effectiveness,there was no statistically significant difference between Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and Endostatin(intravenous drip)+chemotherapeutic drug(thoracic perfusion or intravenous drip),and Endostatin(thoracic perfusion)and chemotherapeutic drug(thoracic perfusion)(P＞0.05);there were statistically differences between Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and Endostatin(thoracic perfusion)[OR=3.44,95％CI(2.29,4.50),P＜0.05],and Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and chemotherapeutic drug(thoracic perfusion)[OR=3.78,95％CI(3.16,4.51),P＜0.05](P＜0.05).The surface under the cumulative ranking curve(SUCRA)showed that Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)＞Endostatin(intravenous drip)+chemotherapeutic drug(thoracic perfusion or intravenous drip)＞Endostatin(thoracic perfusion)＞chemotherapeutic drug(thoracic perfusion)＞chemotherapeutic drug(intravenous drip).In terms of adverse effects,such as gastrointestinal reaction,and reduction of white blood cells and platelets,there was no statistically significant difference among the different interventions(P＞0.05).Conclusion Endostatin either by pleural instillation or combined with first-line chemotherapy drugs significantly improves clinical efficacy in malignant pleural effusion in NSCLC,and it is better and safer with thoracic perfusion efficacy.

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.