ObjectiveTo investigate the mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos（FF） in the treatment of acute lung injury（ALI） by investigating the effects of FF on serum metabolomics of rats with ALI. MethodsThirty male SD rats were acclimated for 1 week， and 6 rats were randomly selected as the blank group. The other 24 rats were injected with lipopolysaccharide（LPS） solution by tracheal drip to establish an ALI model. After successful model establishment， the rats were randomly divided into the model group， the FF low-dose group（3.0 g·kg^-1）， the FF high-dose group（6.0 g·kg^-1）， and the dexamethasone group（5 mg·kg^-1）， with six rats in each group. The FF low- and high-dose groups and the dexamethasone group were received daily oral administration of the corresponding drug solution， and the blank group and the model group were gavaged with an equal amount of saline， treatment was administered continuously for 3 d. The pathological conditions of rat lung tissues were evaluated by hematoxylin-eosin（HE） staining， wet/dry mass ratio（W/D） of the lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. Metabolomic analysis of rat serum was performed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， combined with multivariate statistical analysis， the potential biomarkers of FF in treating ALI were screened by variable importance in the projection（VIP） value>1， P<0.05 from t-test， and log₂fold change（FC）>1 or log₂FC<-1. Kyoto Encyclopedia of Genes and Genomes（KEGG） database combined with MetaboAnalyst were used for pathway analysis of the screened differential metabolites. The protein expression levels of sphingosine-1-phosphate（S1P）， phosphatidylinositol 3-kinase（PI3K）， protein kinase B1（Akt1）， and phosphorylated Akt1（p-Akt1） were examined by Western bolt. The expression levels of interleukin（IL）-6， IL-1β， and tumor necrosis factor（TNF）-α in BALF were detected by enzyme-linked immunosorbent assay（ELISA）. ResultsCompared with the blank group， rats in the model group showed ALI pathological features such as alveolar lumen dilatation， interstitial hemorrhage and massive inflammatory cell infiltration， and the protein concentration in BALF and W/D of the lung tissues were significantly elevated（P<0.01）. Compared with the model group， the low- and high-dose groups of FF as well as the dexamethasone group exhibited reduced pulmonary bronchial hemorrhage in rats， and the protein concentration in BALF and W/D were significantly decreased（P<0.05）， and the lung injury was significantly alleviated. Analysis of rat serum metabolomics revealed that FF downregulated 38 biomarkers. Pathway enrichment analysis showed that FF primarily exerted therapeutic effects through 7 key metabolic pathways， including arginine biosynthesis， sphingomyelin metabolism， alanine， aspartate and glutamate metabolism， taurine and hypotaurine metabolism， α-linolenic acid metabolism， niacin and nicotinamide metabolism， and retinol metabolism. The results of Western bolt and ELISA showed that， compared with the blank group， the model group exhibited significantly elevated expression levels of S1P， PI3K， Akt1 and p-Akt1 proteins in the lung tissues， as well as increased expression levels of IL-6， IL-1β and TNF-α in BALF（P<0.01）. Compared with the model group， the expression levels of the aforementioned indicators were significantly downregulated in the low- and high-dose FF groups as well as the dexamethasone group（P<0.05， P<0.01）. ConclusionFF may play a role in ALI by regulating amino acid metabolism and lipid metabolism， and its mechanism may be related to the inhibition of S1P/PI3K/Akt1 signaling pathway to attenuate the inflammatory response caused by ALI.

Adenoviridae ; genetics ; Ebolavirus ; genetics ; pathogenicity ; Gene Transfer Techniques ; Genetic Vectors ; therapeutic use ; Glycoproteins ; genetics ; HEK293 Cells ; Hemorrhagic Fever, Ebola ; genetics ; pathology ; virology ; Humans ; Inflammation ; genetics ; pathology ; virology ; Mucins ; genetics ; Transfection ; Viral Envelope Proteins ; genetics

Objective To investigate the maximum-tolerated dose (MTD) of cisplatin in docetaxel,cisplatin,and fluorouracil (TPF) induction chemotherapy followed by intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy as well as the safety and short-term efficacy of TPF induction chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma (NPC).Methods Thirtythree patients with locally advanced NPC were enrolled in this trial.The MTD of cisplatin was determined by dose escalation study,and the short-term efficacy and toxicities were evaluated.Results When the doses of docetaxel and fluorouracil were 60 mg/m2 d1 and 550 mg/m2 d1-5,respectively,the MTD of cisplatin was 65 mg/m2 d1.In this regimen (repeated every 3 weeks),grade 3-4 toxicities included neutropenia (67％),febrile neutropenia (9％),diarrhea (21％),and oral mucositis (6％).Except those who experienced dose-limited toxicity,other patients completed the whole treatment schedule.After TPF induction chemotherapy,the overall response rate was 97％,and the complete response rate was 21％.Conclusions In the endemic areas of NPC,induction chemotherapy with docetaxel (60 mg/m2 d1),cisplatin (65 mg/m2 d1),and fluorouracil (550 mg/m2 d1-5),which is repeated every 3 weeks,is proved safe and effective for Asian patients with locally advanced NPC.

This study is to observe the effect of N-(3-phenylallylidene)-6-fluoro-1, 8-(2, 1-propoxy)-7-(4-methylpiperazin-1-yl)-quinolin-4(1H)-one-3-carbonyl hyarazine (FQ16) on apoptosis of hepatocarcinoma SMMC-7721 cells in vitro. With different concentrations of FQ16 at different times used to treat SMMC-7721 cells in vitro, the proliferation of the cells and the inhibition effect of FQ16 on the cell proliferation were examined by MTT assay. Cell apoptosis was determined by Hoechst 33258/PI fluorescence staining, TUNEL and agarose gel electrophoresis method. The effect of FQ16 on topoisomerase II activity was measured by agarose gel electrophoresis using Plasmid pBR322 DNA as the substrate. Mitochondrial membrane potential (MMP, delta psi m) was measured by high content screening image system. The reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression changes of Bcl-2 mRNA and Bax mRNA. The caspase-9, caspase-8, caspase-3, p53, Bcl-2 and Bax protein expressions were detected by Western blotting analysis. The results showed that the cell proliferation was inhibited by FQ16 at 0.625 - 10 micromol L(-1) in a time-dose dependent manner. Treatment of SMMC-7721 cells with different concentrations of FQ16 for 24 h increased the percentage of the apoptosis cells obviously (P<0.05), the typical ladder DNA in apoptotic cells and a concomitant dissipation of the mitochondrial membrane potential. Compared with control group, FQ16 influenced obviously DNA topoisomerase II activity, stimulated DNA cleavage and inhibited DNA reunion mediated by topoisomerase II. In addition, FQ16 (3 - 7.39 micromol L(-1)) increased mRNA expression of Bax and protein expression of p53, Bax, caspase-9, caspase-3, separately, and induced cytosolic accumulation of activities caspase-9 and caspase-3, whereas the mRNA and protein expression of Bcl-2 decreased with no change of caspase-8. Therefore it can be concluded that the effects of inhibited topoisomerase II and mitochondrial-dependent pathways were involved in FQ16 induction of apoptosis of SMMC-7721 cells.