ObjectiveQi deficiency and phlegm dampness syndrome is a common type of clinical traditional Chinese medicine（TCM） syndrome. However， there is no standard， scientific， and accurate report on the construction of animal models of Qi deficiency and phlegm dampness syndrome. This study aims to construct a mouse model of Qi deficiency and phlegm dampness syndrome by using a multi-factor composite modeling method and to evaluate the model. MethodsTwenty-one C57BL/6 mice were randomly divided into three groups with seven mice in each group， which were the normal group， model group， and Shenling Baizhusan （SLBZ） group. The control group was fed with ordinary diet and kept in a normal environment. The model group and SLBZ group were fed with a high-fat diet in a high-humidity environment. Swimming with heavy weights until exhaustion and gavage with cold water or lard were used to establish the mouse model of Qi deficiency and phlegm dampness syndrome. In order to test the syndrome by prescription， mice in the SLBZ group were treated with SLBZ for 14 days after model construction. The exhaustive swimming time， body weight， serum lipid levels， tongue changes， "Qi deficiency and phlegm dampness" assessment scale score， and cecal index of mice in each group were measured. The feces of each group of mice were sent for metagenomics and metabolome sequencing， and the changes in intestinal flora and metabolites were analyzed. ResultsAfter the modeling of Qi deficiency and phlegm dampness syndrome， the exhaustive swimming time of mice was obviously shortened （P<0.01）. The serum total cholesterol， low density lipoprotein cholesterol， and non-high density lipoprotein cholesterol of mice were significantly increased （all P<0.01）. The tongue of mice was significantly different from that of the normal group， and the score of the assessment scale was significantly higher than that of the control group （P<0.01）. Cecal index decreased significantly （P<0.01）. The serum lipid level， tongue image， assessment scale score， and cecal index were reversed in the SLBZ group. Metagenomic and metabolome sequencing results showed that intestinal flora and fecal metabolites were significantly changed in mice with Qi deficiency and phlegm dampness syndrome. Akkermansia_muciniphila， Faecalibaculum_rodentium， Eubacterium_plexicaudatum， Eubacterium sp 14_2， Candida glabrata， Romboutsia_ilealis， Turicibacter sp TS3， and other bacteria had significant changes， and the expressions of intestinal metabolites such as chenodeoxycholic acid， choline， L-phenylalanine betaine， and 2-phenylbutyric acid were significantly changed. Related metabolic pathways such as linoleic acid metabolism， primary bile acid biosynthesis， lysine degradation， arginine biosynthesis， and alpha-linolenic acid metabolism were affected. ConclusionThe Qi deficiency and phlegm dampness model of mice can be constructed by the multi-factor composite modeling method of high-fat diet feeding， high-humidity environment feeding， exhaustive swimming with heavy weight， and intragastric administration with cold water or lard. The blood lipid level， tongue change， score of "Qi deficiency and phlegm dampness assessment scale"， cecal index， and changes in related intestinal flora and metabolites of mice can be used as key indicators for model evaluation.

OBJECTIVE To analyze the effect of Huanglian Jiedu Decoction(HLJDD)on the intestinal flora and metabolites of Parkinson's disease(PD)model mice,and explore the mechanism of HLJDD in intervening in PD based on 16S rRNA technology and non-targeted metabolomics technology.METHODS The PD model of mice was induced by subcutaneous injection of MPTP 20 mg·kg-1·d-1 and peritoneal injection of probenecid 200 mg·kg-1·d-1,and the weight and behavior indexes of mice were measured after drug intervention.HPLC-QTRAP-MS/MS technique was used to detect the levels of neurotransmitters in the striatum of mice.The levels of striatal inflammatory factors were detected by ELISA.The changes of intestinal flora in mice were analyzed by 16S rRNA technology.UHPLC-Q-TOF-MS was used to detect endogenous metabolites in mouse striatum,Orthogonal partial least squares discriminant analysis(OPLS-DA)was adopted to screen potential differential metabolites,and MetaboAnalyst 5.0 was introduced to predict metabolic pathways associated with PD.RESULTS HLJDD significantly improved the motor symptoms and neuroinflammation of PD mice(P<0.01),regulated the level of neurotransmitters,and corrected the intestinal microbiota disorder of PD mice,manifes-ted by the increase of intestinal microbial diversity and the restoration of microbiota profile.After treatment with HLJDD,the abun-dance of Prevotella and Akkermansia in PD mice was significantly increased,and the abundance of Clostridium was decreased(P<0.01).The abnormal metabolite levels were restored mainly by regulating the tryptophan metabolic pathway in the feces and striatum of PD model mice.CONCLUSION HLJDD can significantly improve the pathological damage of PD model mice,and the regulation of disordered intestinal flora and tryptophan metabolism pathway may be the potential mechanism of HLJDD to intervene in PD.

Kaempferol,a natural flavonoid compound,can be extracted from various traditional Chinese medicine,fruits and vegetables.It possesses effective physiological activity,low toxicity and low side effects.It has been revealed by the research results that kaempferol exhibits obvious preventive and inhibitory effects on many common cancers,such as colon cancer,breast cancer,leukemia,etc..The anti-tumor effects are mainly exerted by blocking cell cycle,inhibiting invasion and migration,inducing cell apoptosis and autophagy,and inhibiting aerobic glycolysis of tumors.Meanwhile,the combination of kaempferol and many drugs can produce synergistic anti-tumor and sensitizing effects.The nano-preparation of kaempferol has significant curative effect in the treatment of tumor,which indicates that kaempferol has a good clinical application prospect.In this work,the pharmacological research progress for anti-tumor effect of kaempferol in recent years was reviewed.This article aims to provide theoretical basis and research ideas for further research of kaempferol.

Macrophages have a leading position in the tumor microenvironment (TME) which paves the way to carcinogenesis. Initially, monocytes and macrophages are recruited to the sites where the tumor develops. Under the guidance of different microenvironmental signals, macrophages would polarize into two functional phenotypes, named as classically activated macrophages (M1) and alternatively activated macrophages (M2). Contrary to the anti-tumor effect of M1, M2 exerts anti-inflammatory and tumorigenic characters. In progressive tumor, M2 tumor-associated macrophages (TAMs) are in the majority, being vital regulators reacting upon TME. This review elaborates on the role of TAMs in tumor progression. Furthermore, prospective macrophage-focused therapeutic strategies, including drugs not only in clinical trials but also at primary research stages, are summarized followed by a discussion about their clinical application values. Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.