Based on ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap high-resolution mass spectrometry(UPLC-Q-Orbitrap HRMS) technology and molecular docking, the bitter-tasting substances(hereafter referred to as "bitter substances") in Cistanche deserticola extract were investigated, and the bitter taste and efficacy relationship was explored to lay the foundation for future research on de-bittering and taste correction. Firstly, UPLC-Q-Orbitrap HRMS was used for the qualitative analysis of the constituents of C. deserticola, and 69 chemical components were identified. These chemical components were then subjected to molecular docking with the bitter taste receptor, leading to the screening of 20 bitter substances, including 6 phenylethanol glycosides, 5 flavonoids, 3 phenolic acids, 2 cycloalkenyl ether terpenes, 2 alkaloids, and 2 other components. Nine batches of fresh C. deserticola samples were collected from the same origin but harvested at different months. These samples were divided into groups based on harvest month and plant part. The bitterness was quantified using an electronic tongue, and the content of six potential bitter-active compounds(pineconotyloside, trichothecene glycoside, tubulin A, iso-trichothecene glycoside, jinshihuaoside, and jingnipinoside) was determined by high-performance liquid chromatography(HPLC). The total content of phenylethanol glycosides, polysaccharides, alkaloids, flavonoids, and phenolic acids was determined using UV-visible spectrophotometry. Chemometric analyses were then conducted, including Pearson's correlation analysis, gray correlation analysis, and orthogonal partial least squares discriminant analysis(OPLS-DA), to identify the bitter components in C. deserticola. The results were consistent with the molecular docking findings, and the two methods mutually supported each other. Finally, network pharmacological predictions and analyses were performed to explore the relationship between the targets of bitter substances and their efficacy. The results indicated that key targets of the bitter substances included EGFR, PIK3CB, and PTK2. These substances may exert their bitter effects by acting on relevant disease targets, confirming that the bitter substances in C. deserticola are the material basis of its bitter taste efficacy. In conclusion, this study suggests that the phenylethanol glycosides, primarily pineconotyloside, mauritiana glycoside, and gibberellin, are the material basis for the "bitter taste" of C. deserticola. The molecular docking technique plays a guiding role in the screening of bitter substances in traditional Chinese medicine(TCM). The bitter substances in C. deserticola not only contribute to its bitter taste but also support the concept of the "taste-efficacy" relationship in TCM, providing valuable insights and references for future research in this area.
Molecular Docking Simulation ; Taste ; Chromatography, High Pressure Liquid ; Cistanche/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Mass Spectrometry

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

Objective To compare the effects of esketamine and magnesium sulfate on hemodynamics,stress reaction and postoperative analgesia in elderly patients undergoing laparoscopic cholecystectomy(LC).Methods The subjects of this study,156 elderly patients who underwent LC from June 2021 to October 2023,were randomly divided into 3 groups,each with 52 cases.15 min prior to anesthesia induction,the esketamine group was administered with esketamine hydrochloride injection 0.20 mg/kg intravenously,magnesium sulfate group received intravenous infusion of magnesium sulfate injection 50.00 mg/kg,and physiological saline group received intravenous infusion of equivalent stroke-physiological saline solution.The heart rate(HR)and blood pressure(BP)of three groups were monitored using a monitor immediately after entering the room(T0),immediately after anesthesia induction(T1),immediately after tracheal intubation(T2),immediately after pneumoperitoneum(T3),immediately after cholecystectomy(T4),and immediately before tracheal extubation(T5).The levels of serum stress reaction indicators[cortisol(Cor)and norepinephrine(NE)]in three groups were tested at T0,T4,and T5 respectively.Intraoperative anesthetic dosage and use of atropine and phenylephrine,sufentanil dosage 24 h after surgery,awakening time,extubation time,and directional force recovery time were compared among the three groups.Patients'pain level was assessed respectively 2,6,12 and 24 h after the operation.Adverse reactions were compared among the three groups.Results The magnesium sulfate group and physiological saline group saw much lower HR,systolic blood pressure(SBP),and diastolic blood pressure(DBP)at T1 than they did at T0,the differences were statistically significant(P<0.05),while the physiological saline group had significant higher HR,SBP,DBP at T2,T3,T4,T5 than it did at T0,the differences were statistically significant(P<0.05).Compared with the esketamine group over the same period,the magnesium sulfate group showed a significant decrease in HR at T1 and T2,and a remarkable decrease in SBP and DBP at T1,the differences were statistically significant(P<0.05).At T1,HR,SBP,and DBP in the physiological saline group were much lower,while the HR,SBP,and DBP in this group at T2,T3,T4,and T5 were obviously higher than those in esketamine group,the differences were statistically significant(P<0.05).The physiological saline group witnessed much higher HR,SBP and DBP at T1,T2,T3,T4,T5 as compared with the magnesium sulfate group over the same period,the differences were statistically significant(P<0.05).All the three groups had significantly higher Cor and NE levels at T4 and T5 than they did at T0(P<0.05).The serum Cor and NE levels at T4 and T5 in the esketamine group and magnesium sulfate group were significantly lower than those in the physiological saline group during the same period,the differences were statistically significant(P<0.05).There was no significant difference in serum Cor and NE levels between the esketamine group and magnesium sulfate group at T4 and T5 over the same period,the differences were not statistically significant(P>0.05).The intraoperative consumption of propofol and remifentanil in the esmketamine group and the magnesium sulfate group were significantly less than those in the physiological saline group,and the esmketamine group was significantly more than the magnesium sulfate group(P<0.05).There were no significant difference in the utilization rate of intraoperative atropine and phenylephrine among the three groups(P>0.05).Sufentanil dosage 24 h after surgery in magnesium sulfate group and esketamine group were less than that of physiological saline group,the differences were statistically significant(P<0.05).However,there was no significant difference in the consumption of sufentanil dosage 24 h after surgery between the magnesium sulfate group and the esmketamine group(P>0.05).Extubation time and directional force recovery time in magnesium sulfate group and esketamine group were shorter than those of physiological saline group,the differences were statistically significant(P<0.05),but the differences were not statistically significant between the magnesium sulfate group and esketamine group(P>0.05).The pain visual analogue scale(VAS)score at 2,6,12,and 24 h after the operation in the esketamine group and magnesium sulfate group were significantly lower than those in the physiological saline group,the differences were statistically significant(P<0.05),but the differences were not statistically significant between the magnesium sulfate group and esketamine group(P>0.05).There was no significant difference in postoperative adverse reactions among the three groups(P>0.05).Conclusion In treating elderly people undergoing LC,esketamine and magnesium sulfate are alike in effects on stabilizing hemodynamics,inhibiting stress reaction,and mitigating postoperative pain.

Objective To compare the effects of esketamine and magnesium sulfate on hemodynamics,stress reaction and postoperative analgesia in elderly patients undergoing laparoscopic cholecystectomy(LC).Methods The subjects of this study,156 elderly patients who underwent LC from June 2021 to October 2023,were randomly divided into 3 groups,each with 52 cases.15 min prior to anesthesia induction,the esketamine group was administered with esketamine hydrochloride injection 0.20 mg/kg intravenously,magnesium sulfate group received intravenous infusion of magnesium sulfate injection 50.00 mg/kg,and physiological saline group received intravenous infusion of equivalent stroke-physiological saline solution.The heart rate(HR)and blood pressure(BP)of three groups were monitored using a monitor immediately after entering the room(T0),immediately after anesthesia induction(T1),immediately after tracheal intubation(T2),immediately after pneumoperitoneum(T3),immediately after cholecystectomy(T4),and immediately before tracheal extubation(T5).The levels of serum stress reaction indicators[cortisol(Cor)and norepinephrine(NE)]in three groups were tested at T0,T4,and T5 respectively.Intraoperative anesthetic dosage and use of atropine and phenylephrine,sufentanil dosage 24 h after surgery,awakening time,extubation time,and directional force recovery time were compared among the three groups.Patients'pain level was assessed respectively 2,6,12 and 24 h after the operation.Adverse reactions were compared among the three groups.Results The magnesium sulfate group and physiological saline group saw much lower HR,systolic blood pressure(SBP),and diastolic blood pressure(DBP)at T1 than they did at T0,the differences were statistically significant(P<0.05),while the physiological saline group had significant higher HR,SBP,DBP at T2,T3,T4,T5 than it did at T0,the differences were statistically significant(P<0.05).Compared with the esketamine group over the same period,the magnesium sulfate group showed a significant decrease in HR at T1 and T2,and a remarkable decrease in SBP and DBP at T1,the differences were statistically significant(P<0.05).At T1,HR,SBP,and DBP in the physiological saline group were much lower,while the HR,SBP,and DBP in this group at T2,T3,T4,and T5 were obviously higher than those in esketamine group,the differences were statistically significant(P<0.05).The physiological saline group witnessed much higher HR,SBP and DBP at T1,T2,T3,T4,T5 as compared with the magnesium sulfate group over the same period,the differences were statistically significant(P<0.05).All the three groups had significantly higher Cor and NE levels at T4 and T5 than they did at T0(P<0.05).The serum Cor and NE levels at T4 and T5 in the esketamine group and magnesium sulfate group were significantly lower than those in the physiological saline group during the same period,the differences were statistically significant(P<0.05).There was no significant difference in serum Cor and NE levels between the esketamine group and magnesium sulfate group at T4 and T5 over the same period,the differences were not statistically significant(P>0.05).The intraoperative consumption of propofol and remifentanil in the esmketamine group and the magnesium sulfate group were significantly less than those in the physiological saline group,and the esmketamine group was significantly more than the magnesium sulfate group(P<0.05).There were no significant difference in the utilization rate of intraoperative atropine and phenylephrine among the three groups(P>0.05).Sufentanil dosage 24 h after surgery in magnesium sulfate group and esketamine group were less than that of physiological saline group,the differences were statistically significant(P<0.05).However,there was no significant difference in the consumption of sufentanil dosage 24 h after surgery between the magnesium sulfate group and the esmketamine group(P>0.05).Extubation time and directional force recovery time in magnesium sulfate group and esketamine group were shorter than those of physiological saline group,the differences were statistically significant(P<0.05),but the differences were not statistically significant between the magnesium sulfate group and esketamine group(P>0.05).The pain visual analogue scale(VAS)score at 2,6,12,and 24 h after the operation in the esketamine group and magnesium sulfate group were significantly lower than those in the physiological saline group,the differences were statistically significant(P<0.05),but the differences were not statistically significant between the magnesium sulfate group and esketamine group(P>0.05).There was no significant difference in postoperative adverse reactions among the three groups(P>0.05).Conclusion In treating elderly people undergoing LC,esketamine and magnesium sulfate are alike in effects on stabilizing hemodynamics,inhibiting stress reaction,and mitigating postoperative pain.

Macrophage-mediated inflammation plays a pivotal role in cardiovascular disease pathogenesis. However, current cell-based models lack a comprehensive understanding of crosstalk between macrophages and cardiomyocytes, hindering the discovery of effective therapeutic interventions. Here, a microfluidic model has been developed to facilitate the coculture of macrophages and cardiomyocytes, allowing for mapping key signaling pathways and screening potential therapeutic agents against inflammation-induced dynamic myocardial injury. Through metabolic profiling and bioinformatic enrichment analysis, the microchip model with dynamic cell-cell crosstalk reveals robust activation of inflammatory and oxidative stress-associated metabolic pathways, closely resembling metabolic profiles of myocardial infarction in both humans and rodents. Furthermore, an integrative screening strategy has been established to screen bioactive natural products precisely, identifying ginsenoside Rb₁ and protocatechualdehyde as promising cardioprotective candidates in vitro and in vivo. Taken together, the microfluidic coculture model advances mechanistic insight into macrophage-mediated cardio-immunology and may accelerate the discovery of therapeutics for myocardial injury.

Objective To investigate the feasibility of translocation of pedicled buccal fat pad in the treatment of the temporomandibular joint ankylosis(TMJA)by measuring the diameter of buccal fat pad and related anatomical structures of the transverse blood vessels,nerves and temporomandibular joint.Methods A total of 40 adult head and neck specimens were randomly divided into group A and group B,with 20 cases in each group.The morphology of the buccal fat pad in group A was observed,and its size and compression diameter through blood vessels and nerves were measured.The anatomical structures of the temporomandibular joint in group B were observed and measured.Results The volume of buccal fat pad in group A was(10.10±1.10)mL on the left side and(9.70±1.50)mL on the right side.The longitudinal axis length of buccal fat pad was(28.18±1.35)mm on the left side and(29.47±1.12)mm on the right side;Transverse axis length of buccal fat pad was(18.56±1.67)mm on the left side and(18.97±1.73)mm on the right side;There are facial artery,facial vein,maxillary artery branch,facial nerve buccal branch and so on through the buccal fat pad.In group B,the sagittal section of the temporomandibular joint disc presented S-type in 15 cases(75.0%),L-type in 3 cases(15.0%),and transitional type in 2 cases(10.0%).Anterior and posterior diameter of the articular disc was(14.42±1.94)mm on the left side and(15.34±1.37)mm on the right side;inside and outside diameter of the articular disc was(20.18±1.77)mm on the left side and(19.57±1.32)mm on the right side.Branches of maxillary artery and superficial temporal artery were respectively distributed within and outside the joint.Conclusion The pedicled buccal fat pad has a constant anatomical position,abundant blood supply,strong tissue repair,anti-infection ability and"buffer pad"function,which can reduce the formation of scar after surgery for TMJA,reduce the postoperative recurrence rate,and contribute to the recovery of joint function after surgery.

Objective This project aimed to study the Miao medicine helleborus thibetanus franchon,including investigating its anti-inflammatory activity in collagen-induced arthritis CIA rats and its mechanism of VEGF/VEGFR2/P38 MAPK pathway regulation.Methods Sixty female Wistar rats were randomly divided into six groups:normal;model;positive drug;and low,medium,high dose groups,with 10 rats in each group.Bovine type Ⅱ collagen solution was injected into the tail of rats to construct the rheumatoid arthritis model,and the positive drug group was given MTX2.0 mg/(kg·d)by gavage once every other day.The three groups of helleborus thibetanus franchon low,medium,and high dose were gavaged with helleborus thibetanus franchon ethanol extract at 0.25,0.5 and 1 g/(kg·d)once a day.The normal and model groups were given an equivalent volume of NaCl solution,with continuous administration lasting for 28 days.During treatment,the general condition of the rats was observed,body weight changes recorded,and foot thickness measured.After treatment and euthanasia,the rats'hind limbs were removed for Micro-CT to detect bone destruction;hematoxylin and eosin staining for pathological investigattion of the synovial membrane;immunohistochemistry to observe neovascularization in the synovium;quantitative reverse-transcription PCR to detect mRNA levels of VEGF-A,VEGFR2,TNF-α in the synovial tissue;and Western Blot to detect the expression of VEGF,VEGFR2,p-P38,p-AKT.The analyses were used to explore the potential mechanisms of action of the Miao medicine helleborus thibetanus franchon in treating rheumatoid arthritis.Results Compared with the normal group,the model group showed significant weight loss(P＜0.01),increased foot swelling(P＜0.01),visible proliferative synovial tissue with inflammatory cell infiltration,erosive lesions on bone surfaces,increased neovascularization in the synovium,and significant bone destruction in Micro-CT,with reduced bone percentage,trabecular thickness,and bone density.The levels of VEGF-A,VEGFR2,TNF-α mRNA and VEGF-A,VEGFR2,p-P38,p-AKT proteins were significantly elevated(P＜0.01).Compared with the model group,the helleborus thibetanus franchon ethanol extract-treated groups showed improvements in these conditions in a dose-dependent manner,with the high-dose group receiving the best effect.There was a significant increase in the rats'body weight(P＜0.05);reduction in foot swelling(P＜0.05);amelioration of synovial and erosive bone lesions;reduction in neovascularization in the synovium;and significantly lower levels of VEGF-A,VEGFR2,and TNF-α mRNA,and VEGF-A,VEGFR2,p-P38,and p-AKT protein(P＜0.01).Conclusions The Miao medicine plant helleborus thibetanus franchon may alleviate joint inflammatory damage in CIA rats by modulating the VEGF/VEGFR2 signaling pathway,thereby exerting therapeutic effects on rheumatoid arthritis.

Objective:To investigate the dynamic changes of oral saliva flow, pH value, and bacterial flora before and after radiotherapy in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiotherapy, and to analyze the influencing factors of severe radioactive oral mucositis.Methods:One hundred NPC patients who received radiotherapy for the first time in the Head and Neck Radiotherapy Ward of Shandong Cancer Hospital and Institute from June 2, 2021 to December 30, 2022 were selected. Oral saliva flow, pH value and bacterial flora were measured at 5 time points, namely before radiotherapy, 15 times of radiotherapy, 35 times of radiotherapy, 1 month and 3 months after radiotherapy in patients with NPC, and the dynamic changes of 3 indicators were analyzed at each time. The factors of the occurrence of severe radioactive oral mucositis in patients with NPC were analyzed by univariate and multivariate logistic regression 15 times of radiotherapy.Results:The saliva flow of patients with NPC before radiotherapy, 15 times of radiotherapy, 35 times of radiotherapy, 1 month after and 3 months after radiotherapy were (16.51±1.29), (8.64±1.31), (5.15±1.14), (4.78±1.36) and (5.67±1.27) ml, respectively, with a statistically significant difference ( F=2 171.94, P<0.001). Oral saliva flow decreased to the lowest level 1 month after radiotherapy and then increased (all P<0.05). The pH values of patients with NPC before radiotherapy, 15 times of radiotherapy, 35 times of radiotherapy, 1 month after and 3 months after radiotherapy were 8.28±0.67, 5.87±0.53, 5.32±0.55, 6.04±0.83, 6.74±0.63, respectively, with a statistically significant difference ( F=370.43, P<0.001). The pH value decreased successively after 15 and 35 times of radiotherapy, and gradually increased 1 month and 3 months after radiotherapy (all P<0.05). There was a statistically significant difference ( χ2=18.24, P<0.001) in the detection rate of pathogenic bacteria in patients with NPC before radiotherapy (6%, 6/100), 15 times of radiotherapy (62%, 62/100), 35 times of radiotherapy (60%, 60/100), 1 month after radiotherapy (40%, 40/100) and 3 months after radiotherapy (29%, 29/100). Compared with before radiotherapy, there were statistically significant differences in the detection rates of pathogenic bacteria between 15 times of radiotherapy and 35 times of radiotherapy ( χ2=1.90, P=0.001; χ2=1.63, P=0.005). There was no statistically significant difference in the detection rate of pathogenic bacteria between 15 times of radiotherapy and 35 times of radiotherapy ( χ2=0.27, P=0.644). Compared with before radiotherapy, there was no statistically significant difference in the detection rate of pathogenic bacteria 1 month after radiotherapy and 3 months after radiotherapy ( χ2=1.30, P=0.024; χ2=0.83, P=0.149). Of 100 cases of NPC radiotherapy, 70 patients developed severe radiation oral mucositis (≥ grade 3). There were statistically significant differences in severe radioactive oral mucositis among patients with different smoking history ( χ2=8.84, P=0.003), alcohol drinking ( χ2=23.94, P<0.001), chemotherapy ( χ2=40.41, P<0.001), oral hygiene ( χ2=8.16, P=0.004), oral pH ( χ2=16.83, P<0.001) and oral pathogens ( χ2=8.80, P=0.003). Multivariate analysis showed that, alcohol drinking ( OR=2.23, 95% CI: 1.98-6.04, P=0.006), chemotherapy ( OR=3.13, 95% CI: 2.62-6.87, P<0.001) and oral pathogens ( OR=3.11, 95% CI: 1.04-9.31, P=0.043) were independent influencing factors for the occurrence of severe radioactive oral mucositis in NPC patients with radiotherapy. Conclusion:The oral saliva flow of patients with NPC decreases gradually from the beginning of radiotherapy to the lowest 1 month after radiotherapy and then increases. The pH value gradually decreases from the beginning of radiotherapy to 35 times of radiotherapy, and gradually increases from 1 month to 3 months after radiotherapy. The detection rate of pathogenic bacteria increases rapidly from the beginning of radiotherapy to 15 times of radiotherapy, and the growth rate is stable from 15 times of radiotherapy to 35 times of radiotherapy, and tended to be normal 1 month after radiotherapy. Drinking history, chemotherapy history and oral pathogens are independent risk factors influencing the occurrence of severe radioactive oral mucositis.

Objective To observe the regulating effect and mechanism of Yichang Sanjie Granules on intestinal flora and immune function in mice with colon cancer.Methods Sixty mice were randomly divided into six groups,i.e.,the normal group,the model group,the low-,medium-and high-dose groups of Yichang Sanjie Granules,and the overexpression of melanoma absent gene 2(AIM2)plasmid(pcDNA-AIM2)intervention group,with 10 mice in each group.Colorectal cancer model was prepared by oxidized azomethine(AOM)/dextran sulfate sodium(DSS)induction method in all groups except normal group.After drug administration,the survival curves of mice in each group were plotted and the tumor volume was calculated;serum levels of immunoglobulin(Ig)G,IgM,interleukin(IL)-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA);peripheral blood levels of CD3+,CD4+,CD8+ T cells were detected by flow cytometry;the splenic index was determined;Hematoxylin-eosin(HE)staining was used to observe the pathological changes in colon tissues;16S-rDNA intestinal flora sequencing was used to detect the α-diversity of intestinal flora and the structure of intestinal flora communities;and protein immunoblotting(Wetsern Blot)was used to detect the protein expressions of AIM2,apoptosis-associated speckled-like protein containing a CARD(ASC),and cystatinase-1(caspase-1)in colon tissues.Results Compared with the normal group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the model group were significantly decreased,and the tumor volume,serum levels of IL-1β and IL-18,peripheral blood level of CD8+,and splenic index were significantly increased(all P＜0.05),and the HE staining results showed the characteristic manifestations of colon cancer;compared with the model group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group were significantly increased,and the tumor volume,serum levels of IL-1β and IL-18,level of peripheral blood CD8+,and splenic index were significantly decreased(all P＜0.05),and the HE staining results showed the manifestations of colon cancer were improved.Compared with the normal group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group,and Ruminiclostridium in the model group were significantly decreased,while the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was increased in the model group(P＜0.05);compared with the model group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group and Ruminiclostridium were significantly increased,and the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was decreased in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group(all P＜0.05).Conclusion Yichang Sanjie Granules can increase autoimmunity and improve intestinal flora structure in mice with colon cancer,and its mechanism is related to the activation of AIM2 inflammatory vesicles.