ObjectiveTo explore the potential mechanism by which Huangqi Baijiang Yiren decoction （HBY） repairs the intestinal mucosal injury in the rat model of ulcerative colitis （UC） via the miR-21/suppressor of cytokine signaling 1 （SOCS1）/Janus kinase 1 （JAK1）/signal transducer and activator of transcription 6 （STAT6） signaling pathway. MethodsSixty SPF-grade male SD rats were randomly assigned into six groups： blank， model， low-dose （3.68 g·kg^-1） HBY， medium-dose （7.35 g·kg^-1） HBY， high-dose （14.5 g·kg^-1） HBY， and mesalazine （0.035 g·kg^-1）， with 10 rats in each group. The rat model of UC was established in other groups except the blank group by 3% dextran sulfate sodium solution. The rats were administrated with corresponding drugs once a day for 7 consecutive days since the 3th day after modeling. The histopathological changes of the colon were observed by hematoxylin-eosin staining， and the Robarts histopathology index （RHI） was scored. Enzyme-linked immunosorbent assay was employed to measure the levels of pro-inflammatory cytokines ［interleukin （IL）-6， IL-18， IL-1β， and tumor necrosis factor-α （TNF-α）］ in the serum. Real-time PCR was employed to determine the mRNA levels of miR-21， SOCS1， JAK1， and STAT6 in the colon tissue. Western blot was employed to determine the protein levels of SOCS1， JAK1， phosphorylated （p）-JAK1， STAT6， p-STAT6， Occludin， and Claudin-1 in the colon tissue. ResultsCompared with the blank group， the model group showed an increase in disease activity index （DAI） （P<0.01）， shortening of colon length （P<0.01）， severe histopathological damage in the colon tissue， and an increase in RHI， rises in serum levels of IL-6， IL-1β， IL-18， and TNF-α （P<0.01）， up-regulation in mRNA levels of miR-21， JAK1， and STAT6 and protein levels of p-JAK1 and p-STAT6 （P<0.01）， and down-regulation in mRNA and protein levels of SOCS1 and protein levels of Occludin and Claudin-1 （P<0.01）. The treatment with HBY reduced the DAI （P<0.01）， alleviated colon shortening and histopathological damage in the colon tissue， decreased the RHI （P<0.01）， lowered the serum levels of IL-6， IL-1β， IL-18， and TNF-α （P<0.01）， down-regulated the mRNA levels of miR-21， JAK1， and STAT6 （P<0.05， P<0.01）， up-regulated the mRNA level of SOCS1 （P<0.05）， up-regulated the protein levels of SOCS1， Occludin， and Claudin-1 （P<0.05， P<0.01）， and down-regulated the protein levels of p-JAK1 and p-STAT6 （P<0.05， P<0.01）. ConclusionHBY may modulate the miR-21/SOCS1/JAK1/STAT6 signaling pathway to suppress inflammatory responses and restore the intestinal mucosal barrier in UC rats.

As essential concepts of the traditional Chinese medicine theory,"deficiency"and"toxin"have been enriched and developed continuously since Huangdi Neijing.By tracing back and combing"deficiency"and"toxin",this paper sums up their relationship,analyzes and explains their basic connotation,and discusses their extension.The"deficiency-toxin"theory has two meanings:it covers the pathological state of the human body with deficiency of vital qi and excess of pathogenic toxin,and it also refers to the pathological evolutionary process in which"deficiency"and"toxin"promote each other.Based on the connotation and dynamic pathogenesis of the"deficiency-toxin"theory,it is pointed out that this theory can be applied to the prevention and treatment of infectious diseases and chronic debilitating diseases,including the"inflammation-cancer transformation"of inflammatory bowel disease.Taking inflammatory bowel disease as an example and combining its Western medical background,this paper expounds on the pathogenesis and treatment of the"inflammation-cancer transformation"of inflammatory bowel disease,and provides a paradigm of"deficiency-toxin"theory guiding clinical research.

Objective The aim of this study was to establish a rat model of inflammation-cancer transformation of inflammatory bowel disease(IBD)and to explore the associated characteristics of the intestinal flora.Methods Adult male Wistar rats were divided randomly into control and model groups(M1,M2,M3)with different dextran sulfate sodium(DSS)intervention cycles.Colitis-cancer transformation was induced in all rats in the model group by a single intraperitoneal injection of azoxymethane(AOM)combined with free drinking of DSS in different cycles,and disease activity index(DAI)scores were recorded.Rats in the M1,M2 and M3 groups were killed at the end of the first,second,and third cycles of DSS,respectively,and spleen and colon tissues and colon contents were collected.Histological damage and colon carcinogenesis were evaluated in each group using hematoxylin and eosin staining and transmission electron microscopy.Characteristic changes in the intestinal flora were analyzed by 16S rRNA sequencing.Results AOM/DSS administration significantly increased the DAI score,shortened the colon,and increased the spleen index.The intestinal mucosal barrier was progressively destroyed from groups M1 to M3,and the pathological score was gradually increased.Abnormal crypt foci,polyps,low-and high-grade intraepithelial neoplasia,and mucosal carcinoma appeared in turn,while the pathological process showed similar characteristics to carcinogenesis in human inflammatory bowel disease.Screening using 16S rRNA sequencing with two differential abundance testing tools,Wilcoxon and ALDEx2,indicated that changes in flora abundance represented by Bacteroidetes and Monoglobus may be involved in the progression of colitis-cancer transformation.The functions of the differential flora were mainly enriched in metabolic pathways,such as lipid and carbohydrate metabolism.Conclusions The current rat model induced by AOM/DSS can dynamically simulate the pathological characteristics of colitis-cancer transformation,accompanied by changes in the abundance of specific intestinal flora,which may be closely related to the metabolic pathways mediated by the flora.

Objective The aim of this study was to establish a rat model of inflammation-cancer transformation of inflammatory bowel disease(IBD)and to explore the associated characteristics of the intestinal flora.Methods Adult male Wistar rats were divided randomly into control and model groups(M1,M2,M3)with different dextran sulfate sodium(DSS)intervention cycles.Colitis-cancer transformation was induced in all rats in the model group by a single intraperitoneal injection of azoxymethane(AOM)combined with free drinking of DSS in different cycles,and disease activity index(DAI)scores were recorded.Rats in the M1,M2 and M3 groups were killed at the end of the first,second,and third cycles of DSS,respectively,and spleen and colon tissues and colon contents were collected.Histological damage and colon carcinogenesis were evaluated in each group using hematoxylin and eosin staining and transmission electron microscopy.Characteristic changes in the intestinal flora were analyzed by 16S rRNA sequencing.Results AOM/DSS administration significantly increased the DAI score,shortened the colon,and increased the spleen index.The intestinal mucosal barrier was progressively destroyed from groups M1 to M3,and the pathological score was gradually increased.Abnormal crypt foci,polyps,low-and high-grade intraepithelial neoplasia,and mucosal carcinoma appeared in turn,while the pathological process showed similar characteristics to carcinogenesis in human inflammatory bowel disease.Screening using 16S rRNA sequencing with two differential abundance testing tools,Wilcoxon and ALDEx2,indicated that changes in flora abundance represented by Bacteroidetes and Monoglobus may be involved in the progression of colitis-cancer transformation.The functions of the differential flora were mainly enriched in metabolic pathways,such as lipid and carbohydrate metabolism.Conclusions The current rat model induced by AOM/DSS can dynamically simulate the pathological characteristics of colitis-cancer transformation,accompanied by changes in the abundance of specific intestinal flora,which may be closely related to the metabolic pathways mediated by the flora.

Objective To study the effect of black granule capsules(BGCs) on growth of transplanted mouse hepatocarcinoma cells, cell proliferation cycle and apoptosis.Methods KM mouse were subcutaneously inoculated with Hepatocarcinoma cells (H22) and randomly divided into the model control group, the positive control group, the low, medium and high does of BGC group after 24h. The positive control group received intraperitoneal injection with 30 mg/kg cyclophosphamide. Mice of BGC groups were intragastricaly with different dosage of BGC (400, 800, 1 600 mg/kg). The model control group received intragastricaly with normal saline. The drugs were administrated once a day for seven days. The tumor inhibition rate was calculated at 24 h after the last administration. Flow cytometry was used to detect changes of cell cycle and apoptosis in harvested H22 tumor cells.Results The group of high does showed significant inhibitory effect on the growth of transplanted H22 tumor cells withthe inhibitory rate 38.78% (male) and 43.57% (female). Compared with model control group, groups of different dosages decreased time of G0-G1 phase (58.06% ± 9.65%, 55.10% ± 5.89%, 61.36% ± 15.95%vs. 74.47% ± 2.63%), increased tiem of Sphase (33.96% ± 11.90%, 32.67% ± 4.04%, 33.89% ± 9.82%vs. 14.37% ± 4.92%), and increased the apoptosis rate (31.12% ± 1.85%, 31.89% ± 2.16%, 40.64% ± 0.55%vs.21.75% ± 2.64%).Conclusion BGC has antitumor effect on mouse hepatocarcinoma H22 tumor cells, and its mechanism was to regulate cell proliferation cycle and induce the apoptosis.