OBJECTIVE To explore the potential mechanisms of astragalin （AG） in allevating ulcerative colitis （UC） in mice through modulation of the intestinal flora. METHODS Male C57BL/6 mice were randomly divided into normal group （CON group）， model group [dextran sodium sulfate （DSS） group]， 5-aminosalicylic acid group （5-ASA group）， AG low-dose group and high-dose group （AGL and AGH groups）， with 8 mice in each group. The mice UC model was established by drinking 3% DSS solution continuously for 7 days in all groups except the CON group. After that， 3% DSS solution was replaced by water， and the mice of each drug group were gavaged with the corresponding drug solution. Mice in the CON and DSS groups were gavaged with an equal volume of normal saline， once a day， for 7 days. After the last gavage， the body weight change index， disease activity index （DAI） score， colon length and spleen index， and levels of inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6） were compared among the mice in each group； pathological changes in colonic tissues of the mice were observed in each group， and the pathological score and the percentage of goblet cells were compared； mRNA expressions of barrier-related factors [occludin and ZO-1] and inflammation-related factors [silencing information regulatory factor 1 （SIRT1）， c-Jun N-terminal kinase （JNK） and p38 mitogen-activated protein kinase （p38 MAPK）] were detected in each group of mice； the changes in the intestinal flora of mice in each group were analyzed and the contents of intestinal metabolites short-chain fatty acids （SCFAs） was determined. Using DSS and AG-treated fecal bacterial liquid as an intervention， the mechanism of anti-UC effect of AG was further verified by a fecal microbiota transplant experiment. RESULTS Compared with the CON group， the intestinal mucosal structure of mice in the DSS group was severely damaged， with obvious infiltration of inflammatory cells collapsing the wall； their body weight change index， colon length， the percentage of goblet cells， mRNA expressions of occludin， ZO-1 and SIRT1， Chao1 and Shannon indexes， and contents of acetic acid and butyric acid were significantly reduced， shortened or down-regulated （P＜0.05）； however， DAI score， spleen index， levels of inflammatory factors， pathological score， as well as mRNA expressions of p38 MAPK and JNK， were all significantly increased or up-regulated （P＜0.05）. Compared with the DSS group， colon tissue lesions of AG mice in all dose groups showed different degrees of improvement， and the above quantitative indexes were generally regressed （P＜0.05）， and the intervention effect of AG-treated fecal bacterial fluid was basically the same as that of AG. CONCLUSIONS AG can improve relevant symptoms in UC mice and reduce their inflammatory response and colonic histopathological changes. The above effects may be related to regulating the diversity of intestinal flora in mice， increasing the contents of butyric acid and propionic acid， and promoting the repair of the colonic mucosal barrier， thus regulating the expressions of genes related to the SIRT1/p38 MAPK inflammatory pathway.

Hyperbranched polymers (HBPs) have drawn great interest in the biomedical field on account of their special morphology, low viscosity, self-regulation, and facile preparation methods. Moreover, their large intramolecular cavities, high biocompatibility, biodegradability, and targeting properties render them very suitable for anti-tumor drug delivery. Recently, exploiting the specific characteristics of the tumor microenvironment, a range of multifunctional HBPs responsive to the tumor microenvironment have emerged. By further introducing various types of drugs through physical embedding or chemical coupling, the resulting HBPs based delivery systems have played a crucial part in improving drug stability, increasing effective drug concentration, decreasing drug toxicity and side effects, and enhancing anti-tumor effect. Here, based on different types of tumor microenvironment stimulation signals such as pH, redox, temperature, etc., we systematically review the preparation and response mechanism of HBPs, summarize the latest advances in drug delivery applications, and analyze the challenges and future research directions for such nanomaterials in biomedical clinical applications.

Objective To explore the protective effect and mechanism of vitamin D combined with puerarin on liver fibrosis.Methods The rats were divided into normal control group (C),tetrachloromethone group (CCl4),vitamin D group (V),puerarin group(P) and vitamin D combined with puerarin group(V+P).After 8 weeks,the rats were sacrificed and blood and liver samples were collected.The level of blood hyaluronic acid(HA) was tested.The hydroxyproline(Hyp) level in the liver was measured.The liver paraffin sections were made and examined by the sirius red staining.The mRNA levels of collagen Ⅰ and collagen Ⅲ in the liver tissue were detected by RT-PCR,and the levels of NF-κB and TNF-α in the liver were detected by Western blot.Results The CCl4 group appeared obvious liver fibrosis.The liver fibrosis degree was significantly improved in the group V,P and V+P,the blood HA level and liver Hyp level were reduced.The mRNA levels of collagen Ⅰ and collagen Ⅲ as well as the protein levels of NF-κB and TNF-α in the liver were significantly decreased.Among them.The liver fibrosis improvement degree in the V+P group was most significant.Conclusion Vitamin D combined with puerarin can protect rat liver fibrosis induced by CCl4 and its mechanism may be related with reducing the activation of hepatic stellate cells(HSC) and decreasing the collagenous fibers secretion.