Objective To investigate the mechanism of Kuijie Ankang Decoction in regulating immune,autophagy and intestinal flora in the treatment of ulcerative colitis(UC).Methods UC mouse model was established by free drinking with sodium dextran sulfate.The mice were randomly divided into blank control group,model group,Kuijie Ankang Decoction group,salazine sulfopyridine(SASP)group and 3-methyladenine(3-MA)group,with 12 mice in each group.Each drug group was given corresponding drugs for gavage,the blank control group and model group were given the same volume of distilled water for gavage for 7 days.The general condition of mice was observed and the disease activity index(DAI)was scored,the morphology of colon tissue was observed by HE staining,the contents of TNF-α,IL-1β,IL-6,IL-8 and IL-10 in colon tissue were detected by ELISA,the mRNA and protein expressions of LC3,Beclin-1 and p62 in colon tissue were detected by RT-qPCR and Western blot,respectively.16S rDNA sequencing was used to analyze the structure of intestinal flora.Results Compared with the blank control group,the mice in the model group showed a decrease in body mass,an increase in DAI score,a decrease in colon length,serious mucosal injury and inflammatory cell infiltration,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue significantly increased(P<0.05,P<0.01),the content of IL-10 decreased(P<0.01),the mRNA expressions of LC3 and Beclin-1 in colon tissue decreased(P<0.05,P<0.01),the mRNA and protein expression of p62 increased(P<0.01),while the expressions of LC3Ⅱ/LC3Ⅰ and Beclin-1 proteins decreased(P<0.05,P<0.01).Compared with the model group,the body mass of mice in Kuijie Ankang Decoction group and SASP group increased(P<0.05),DAI score decreased(P<0.05),the colon length increased(P<0.05),the pathological damage of colon mucosa was alleviated,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue decreased(P<0.05,P<0.01),the content of IL-10 increased(P<0.01),the expressions of LC3 and Beclin-1 mRNA in colon tissue increased(P<0.05,P<0.01),the expression of p62 mRNA and protein decreased(P<0.05,P<0.01),the expressions of LC3Ⅱ/LC3Ⅰand Beclin-1 protein increased(P<0.05,P<0.01).16S rDNA sequencing results showed that the diversity and evenness of the intestinal flora in the model group mice decreased,with a decrease in the relative abundance of Firmicutes,Actinobacteria and Patescibacteria(P<0.05),and an increase in the relative abundance of Bacteroidota,Verrucomicrobiota and Proteobacteria(P<0.05);the relative abundance of Bacilli and Coriobacteriia decreased(P<0.05),the relative abundance of Bacteroidia,Clostridia and Verrucomicrobiae increased(P<0.05);the relative abundance of Ligilactobacillus and Dubosiella decreased(P<0.05),the relative abundance of unclassified Muribaculaceae,Lachnospiraceae NK4A136_group,Akkermansia and unclassified Lachnospiraceae increased(P<0.05).Compared with the model group,the diversity and evenness of intestinal flora increased in Kuijie Ankang Decoction group and SASP group,with an increase in the relative abundance of Firmicutes(P<0.05),a decrease in the relative abundance of Bacteroidota and Verrucomicrobiota(P<0.05),the relative abundance of Bacteroidia and Bacilli increased(P<0.05),the relative abundance of Verrucomicrobiae decreased(P<0.05);the relative abundance of unclassified Muribaculaceae and Ligilactobacillus increased(P<0.05),while the relative abundance of Lachnospiraceae NK4A136_group and Akkermansia decreased(P<0.05).Conclusion Kuijie Ankang Decoction can significantly improve the intestinal mucosal injury of UC mice,and the mechanism may be related to the regulation of colon autophagy level and intestinal flora disorder.

Objective:To explore the therapeutic effect of compound Kuijie Ankang Decoction on ulcerative colitis (UC) model mice by non targeted metabonomics; To explore its mechanism.Compound Kuijie Ankang.Methods:The mice were randomly divided into blank control group, model group, Kuijie Ankang Decoction group and sulfasalazine group, with 12 mice in each group. Except the blank control group, the other groups were given 1.5% DSS solution for free drinking to prepare UC model. After successful modeling, Kuijie Ankang Decoction group was intragastrically administered with compound Kuijie Ankang Decoction of 9.68 g/kg, sulfasalazine group was intragastrically administered with sulfasalazine capsule suspension of 320 mg/kg, model group and blank control group were intragastrically administered with equal volume of purified water, once a day, for 7 consecutive days. The body mass and disease activity index (DAI) score of mice were measured. ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the colon tissue of mice; the protein expressions of Claudin-1 and Zo-1 in colon tissue were detected by immunofluorescence method. HE staining was used to observe the pathological changes in the colon, and UHPLC-OE-MS technology was used to analyze the endogenous metabolite structure of mouse colon tissue, differential metabolites and related metabolic pathways were screened.Results:Compared with the model group, the colon length in Kuijie Ankang Decoction group and sulfasalazine group increased ( P<0.01), the DAI score decreased ( P<0.01), the levels of TNF-α, IL-1β and IL-6 in colon tissue decreased ( P<0.01), the level of IL-10 increased ( P<0.01), and the average optical density of Claudin-1 and Zo-1 protein increased ( P<0.01 or P<0.05). Metabolomics analysis identified 26 potential differential metabolites, including nicotinamide adenine dinucleotide, guanine, gamma aminobutyric acid, and thiamine, affecting 26 key metabolic pathways, including lysine biosynthesis, thiamine metabolism, cysteine and methionine metabolism. Conclusion:Kuaijie Ankang Decoction may improve metabolites such as Gamma aminobutyric acid and thiamine through metabolic pathways such as lysine biosynthesis to alleviate inflammatory reactions, thereby exerting therapeutic effects on ulcerative colitis in mice.

Objective To investigate the mechanism of Kuijie Ankang Decoction in regulating immune,autophagy and intestinal flora in the treatment of ulcerative colitis(UC).Methods UC mouse model was established by free drinking with sodium dextran sulfate.The mice were randomly divided into blank control group,model group,Kuijie Ankang Decoction group,salazine sulfopyridine(SASP)group and 3-methyladenine(3-MA)group,with 12 mice in each group.Each drug group was given corresponding drugs for gavage,the blank control group and model group were given the same volume of distilled water for gavage for 7 days.The general condition of mice was observed and the disease activity index(DAI)was scored,the morphology of colon tissue was observed by HE staining,the contents of TNF-α,IL-1β,IL-6,IL-8 and IL-10 in colon tissue were detected by ELISA,the mRNA and protein expressions of LC3,Beclin-1 and p62 in colon tissue were detected by RT-qPCR and Western blot,respectively.16S rDNA sequencing was used to analyze the structure of intestinal flora.Results Compared with the blank control group,the mice in the model group showed a decrease in body mass,an increase in DAI score,a decrease in colon length,serious mucosal injury and inflammatory cell infiltration,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue significantly increased(P<0.05,P<0.01),the content of IL-10 decreased(P<0.01),the mRNA expressions of LC3 and Beclin-1 in colon tissue decreased(P<0.05,P<0.01),the mRNA and protein expression of p62 increased(P<0.01),while the expressions of LC3Ⅱ/LC3Ⅰ and Beclin-1 proteins decreased(P<0.05,P<0.01).Compared with the model group,the body mass of mice in Kuijie Ankang Decoction group and SASP group increased(P<0.05),DAI score decreased(P<0.05),the colon length increased(P<0.05),the pathological damage of colon mucosa was alleviated,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue decreased(P<0.05,P<0.01),the content of IL-10 increased(P<0.01),the expressions of LC3 and Beclin-1 mRNA in colon tissue increased(P<0.05,P<0.01),the expression of p62 mRNA and protein decreased(P<0.05,P<0.01),the expressions of LC3Ⅱ/LC3Ⅰand Beclin-1 protein increased(P<0.05,P<0.01).16S rDNA sequencing results showed that the diversity and evenness of the intestinal flora in the model group mice decreased,with a decrease in the relative abundance of Firmicutes,Actinobacteria and Patescibacteria(P<0.05),and an increase in the relative abundance of Bacteroidota,Verrucomicrobiota and Proteobacteria(P<0.05);the relative abundance of Bacilli and Coriobacteriia decreased(P<0.05),the relative abundance of Bacteroidia,Clostridia and Verrucomicrobiae increased(P<0.05);the relative abundance of Ligilactobacillus and Dubosiella decreased(P<0.05),the relative abundance of unclassified Muribaculaceae,Lachnospiraceae NK4A136_group,Akkermansia and unclassified Lachnospiraceae increased(P<0.05).Compared with the model group,the diversity and evenness of intestinal flora increased in Kuijie Ankang Decoction group and SASP group,with an increase in the relative abundance of Firmicutes(P<0.05),a decrease in the relative abundance of Bacteroidota and Verrucomicrobiota(P<0.05),the relative abundance of Bacteroidia and Bacilli increased(P<0.05),the relative abundance of Verrucomicrobiae decreased(P<0.05);the relative abundance of unclassified Muribaculaceae and Ligilactobacillus increased(P<0.05),while the relative abundance of Lachnospiraceae NK4A136_group and Akkermansia decreased(P<0.05).Conclusion Kuijie Ankang Decoction can significantly improve the intestinal mucosal injury of UC mice,and the mechanism may be related to the regulation of colon autophagy level and intestinal flora disorder.

Objective:To observe the curative effect and temperature safety management of ginger mud moxibustion of different thickness on ankylosing spondylitis patients with kidney yang deficiency type, and to explore the best curative effect combination and safety combination of ginger mud thickness in Du Meridian moxibustion.Methods:From March 2020 to March 2021, 90 patients with ankylosing spondylitis of kidney yang deficiency type who were treated with Du moxibustion in the Affiliated Hospital of Nanjing University of Chinese Medicine were selected. According to the thickness of ginger paste, they were randomly divided into 2 cm-thick ginger mud thickness group, 3 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group when the diameter and height of moxa wool were the same as 2 cm, 30 cases in each group. They were treated with Fu Yang Du moxibustion once a week for 60 minutes each time. Visual Analogue Scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), traditional Chinese medicine syndrome score were used to evaluate the curative effect of spinal function before and after the intervention for 6 weeks. The time when moxibustion temperature reached 43 ℃ and moxibustion temperature maintained at 43-45 ℃ were analyzed for safety evaluation.Results:After moxibustion, VAS scores of 2 cm-thick ginger mud thickness group, 3 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group were 2.89 ± 0.96, 2.01 ± 0.69, 2.93 ± 1.23, BASDAI scores were 3.51 ± 0.94, 2.69 ± 0.68, 3.13 ± 0.96 and BASFI scores were 1.71 ± 0.99, 0.99 ± 0.36, 1.61 ± 0.50, the traditional Chinese medicine syndrome scores were 15.97 ± 4.61, 12.08 ± 3.21, 13.79 ± 3.58. The scores of the three groups were statistically significant ( F values were 6.51-19.22, all P<0.05) . After the intervention, there were significant differences in the scores between 2 cm-thick ginger mud thickness group and 3 cm-thick ginger mud thickness group, 2 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group, 3 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group ( t values were -6.61-4.56, all P<0.05). Conclusions:Du moxibustion is an effective method to treat ankylosing spondylitis of kidney yang deficiency type. The best curative effect and safety combination is moxa velvet diameter height 2 cm, ginger mud thickness 3 cm.

[Abstract] In recent years, tumor immunotherapy has developed rapidly, among which T-cell-based adoptive cell therapy has achieved certain clinical effect and become one of the most potential immunotherapeutics. T cell infiltration mainly includes rolling, adhesion, extravasation and chemotaxis etc. However, there are physical barriers, chemokine mismatch, vascular abnormalities, immunosuppressive microenvironment and other factors that limit the efficacy of adoptive cell therapy. The homing ability of T cells can be further improved by optimizing the chemokine receptor on the cell surface, inserting targeted peptide, improving the way of administration, and adopting combined treatment of radiotherapy, immune checkpoint blocker, tumor vaccine and bispecific antibody, etc. This review mainly summarizes the process of T cell infiltration, the influencing factors of T cell targeting tumor site and the relevant treatment strategies, as well as gives a prospection for future research.

Building a harmonious relationship between doctors and patients must resolve disharmony.Above all,resolving disharmony must clear about the most important reason that results in disharmony is not to know that patients play the most important role in the doctors' curing process.So far doctors and patients must make a point of the most important role of patients.Doctors must leave no stone unturned to mobilize patients' go-aheadism.Patients must positively cooperate with doctors,exert the most important role to cure and return to health.