1.Prevalence survey of surgical site infections among orthopedics department patients of 61 traditional Chinese hospitals in Guangdong Province
Caijuan LUO ; Wenhui LI ; Hao HE ; Dawen YANG
Chinese Journal of Nosocomiology 2025;35(9):1378-1384
OBJECTIVE To conduct a survey of current status of surgical site infections(SSIs)among the orthope-dics department patients in the traditional Chinese hospitals of Guangdong Province so as to provide guidance for prevention and control of the SSIs.METHODS A retrospective questionnaire survey and field verification were car-ried out for the prevalence of SSIs among the orthopedics department patients of 61 secondary or above traditional Chinese hospitals(traditional Chinese medicine integrated with western medicine hospitals)in 2019.RESULTS To-tally 35 tertiary hospitals and 26 secondary hospitals were involved in the survey.A total of 167,051 patients who re-ceived orthopedic surgical procedures were investigated,355 of whom had SSIs,with the incidence 0.21%.The patients who had superficial surgical incision infections were dominant,accounting for 53.52%.The incidence rates of SSIs of grade 3 surgeries and SSIs of type Ⅰ incision were respectively 0.34%and 0.24%in the secondary hospitals,remarkably higher than those in the tertiary hospitals(all P<0.05).There were no signficant differences in the incidence rate of SSIs of other grades of surgeries between the secondary hospitals and the tertiary hospitals.There were significant differences in the nutrition status,smoking history,complication with COPD,anemia,bath 1 night before surgery,preoperative pe-ripheral blood total white blood cell counts,type of surgery,title of surgeon,operating room,anesthesia mode,surgical site disinfectants,operation duration,American Society of Anesthesiologists(ASA)score and surgical risk index between the tertiary hospitals and the secondary hospitals(all P<0.05).The etiological test was carried out for 331 patients with SSIs;totally 266 strains of pathogens were isolated,105(39.47%)of which were Staphylococcus aureus.CONCLUSIONS The incidence of SSIs is relatively low among the orthopedics department patients of the traditional Chi-nese hospitals(traditional Chinese medicine integrated with western medicine hospitals)in Guangdong Province.The inci-dence rates of SSIs of grade 3 surgeries and SSIs of type Ⅰ incision are remarkably higher in the secondary hospitals than in the tertiary hospitals.It is necessary to take comprehensive prevention and treatment measures according to the character-istics of the infections so as to reduce the incidence of SSIs among the orthopedics department patients.
2.Effect of circular RNA circ_0004535 on type 2 diabetes mellitus combined with metabolism-related fatty liver disease model mice
Caijuan ZHOU ; Min LI ; Hui XU ; Bingru CHEN ; Qing MENG ; Wei XIONG
Chinese Journal of Comparative Medicine 2025;35(8):78-93
Objective To explore the influence of hsa_circ_0004535 on type 2 diabetes(T2DM)combined with metabolic-associated fatty liver disease(MAFLD)model mice.Methods Forty-eight healthy SPF grade Balb/c mice were selected for modeling and divided into the following groups(n=6 per group):Control group:normal feed;T2DM group:diabetes model induced by high-glucose and high-fat diet;T2DM combined MAFLD group:non-alcoholic fatty liver high-glucose and high-fat diet-induced diabetes combined with fatty liver model;T2DM combined MAFLD+hsa_circ_NC group:after 4 weeks of modeling,10 nmol hsa_circ_NC injected into the tail vein;T2DM combined MAFLD+hsa_circ_0004535 group:after 4 weeks of modeling,10 nmol circ_0004535 injected into the tail vein;T2DM combined MAFLD+miRNA_NC group:after 4 weeks of modeling,10 nmol miRNA blank control injected into the tail vein;T2DM combined MAFLD+miR-1827 agomir group:after 4 weeks of modeling,10 nmol miR-1827 agomir injected into the tail vein;and T2DM combined MAFLD+miR-1827 antagomir group:after 4 weeks of modeling,10 nmol miR-1827 antagomir injected into the tail vein.Mouse body weight was measured after the interventions and recorded weekly.Glucose and insulin tolerance tests were performed,blood lipids and liver function were measured,the liver and insulin resistance indexes were calculated,and pathological tests(hematoxylin/eosin(HE),oil red O,and Masson staining,immunohistochemistry,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL))were performed to measure the degree of hepatic inflammation,fat deposition,and fibrosis.Results(1)Body weight,liver weight,liver index,insulin resistance index,and biochemical indexes were all significantly lower in the hsa_circ_0004535 injection group compared with the hsa_circ_NC injection group and the T2DM combined MAFLD group(both P<0.05).(2)Steatosis vacuoles were reduced and smaller and inflammatory cell infiltration was reduced in the T2DM combined MAFLD+circ_0004535 group,as shown by HE and oil red staining.(3)TUNEL-positive cells were significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group(P<0.05).(4)Collagen fiber deposition was significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group,as shown by Masson staining(P<0.05).Conclusions The expression of hsa_circ_0004535 and miRNA-1827 play important roles in regulating lipid metabolism,insulin sensitivity,inflammatory pathways,hepatocyte apoptosis,and hepatic fibrosis-related pathways in an animal model of T2DM combined with MAFLD.
3.Prevalence survey of surgical site infections among orthopedics department patients of 61 traditional Chinese hospitals in Guangdong Province
Caijuan LUO ; Wenhui LI ; Hao HE ; Dawen YANG
Chinese Journal of Nosocomiology 2025;35(9):1378-1384
OBJECTIVE To conduct a survey of current status of surgical site infections(SSIs)among the orthope-dics department patients in the traditional Chinese hospitals of Guangdong Province so as to provide guidance for prevention and control of the SSIs.METHODS A retrospective questionnaire survey and field verification were car-ried out for the prevalence of SSIs among the orthopedics department patients of 61 secondary or above traditional Chinese hospitals(traditional Chinese medicine integrated with western medicine hospitals)in 2019.RESULTS To-tally 35 tertiary hospitals and 26 secondary hospitals were involved in the survey.A total of 167,051 patients who re-ceived orthopedic surgical procedures were investigated,355 of whom had SSIs,with the incidence 0.21%.The patients who had superficial surgical incision infections were dominant,accounting for 53.52%.The incidence rates of SSIs of grade 3 surgeries and SSIs of type Ⅰ incision were respectively 0.34%and 0.24%in the secondary hospitals,remarkably higher than those in the tertiary hospitals(all P<0.05).There were no signficant differences in the incidence rate of SSIs of other grades of surgeries between the secondary hospitals and the tertiary hospitals.There were significant differences in the nutrition status,smoking history,complication with COPD,anemia,bath 1 night before surgery,preoperative pe-ripheral blood total white blood cell counts,type of surgery,title of surgeon,operating room,anesthesia mode,surgical site disinfectants,operation duration,American Society of Anesthesiologists(ASA)score and surgical risk index between the tertiary hospitals and the secondary hospitals(all P<0.05).The etiological test was carried out for 331 patients with SSIs;totally 266 strains of pathogens were isolated,105(39.47%)of which were Staphylococcus aureus.CONCLUSIONS The incidence of SSIs is relatively low among the orthopedics department patients of the traditional Chi-nese hospitals(traditional Chinese medicine integrated with western medicine hospitals)in Guangdong Province.The inci-dence rates of SSIs of grade 3 surgeries and SSIs of type Ⅰ incision are remarkably higher in the secondary hospitals than in the tertiary hospitals.It is necessary to take comprehensive prevention and treatment measures according to the character-istics of the infections so as to reduce the incidence of SSIs among the orthopedics department patients.
4.Effect of circular RNA circ_0004535 on type 2 diabetes mellitus combined with metabolism-related fatty liver disease model mice
Caijuan ZHOU ; Min LI ; Hui XU ; Bingru CHEN ; Qing MENG ; Wei XIONG
Chinese Journal of Comparative Medicine 2025;35(8):78-93
Objective To explore the influence of hsa_circ_0004535 on type 2 diabetes(T2DM)combined with metabolic-associated fatty liver disease(MAFLD)model mice.Methods Forty-eight healthy SPF grade Balb/c mice were selected for modeling and divided into the following groups(n=6 per group):Control group:normal feed;T2DM group:diabetes model induced by high-glucose and high-fat diet;T2DM combined MAFLD group:non-alcoholic fatty liver high-glucose and high-fat diet-induced diabetes combined with fatty liver model;T2DM combined MAFLD+hsa_circ_NC group:after 4 weeks of modeling,10 nmol hsa_circ_NC injected into the tail vein;T2DM combined MAFLD+hsa_circ_0004535 group:after 4 weeks of modeling,10 nmol circ_0004535 injected into the tail vein;T2DM combined MAFLD+miRNA_NC group:after 4 weeks of modeling,10 nmol miRNA blank control injected into the tail vein;T2DM combined MAFLD+miR-1827 agomir group:after 4 weeks of modeling,10 nmol miR-1827 agomir injected into the tail vein;and T2DM combined MAFLD+miR-1827 antagomir group:after 4 weeks of modeling,10 nmol miR-1827 antagomir injected into the tail vein.Mouse body weight was measured after the interventions and recorded weekly.Glucose and insulin tolerance tests were performed,blood lipids and liver function were measured,the liver and insulin resistance indexes were calculated,and pathological tests(hematoxylin/eosin(HE),oil red O,and Masson staining,immunohistochemistry,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL))were performed to measure the degree of hepatic inflammation,fat deposition,and fibrosis.Results(1)Body weight,liver weight,liver index,insulin resistance index,and biochemical indexes were all significantly lower in the hsa_circ_0004535 injection group compared with the hsa_circ_NC injection group and the T2DM combined MAFLD group(both P<0.05).(2)Steatosis vacuoles were reduced and smaller and inflammatory cell infiltration was reduced in the T2DM combined MAFLD+circ_0004535 group,as shown by HE and oil red staining.(3)TUNEL-positive cells were significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group(P<0.05).(4)Collagen fiber deposition was significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group,as shown by Masson staining(P<0.05).Conclusions The expression of hsa_circ_0004535 and miRNA-1827 play important roles in regulating lipid metabolism,insulin sensitivity,inflammatory pathways,hepatocyte apoptosis,and hepatic fibrosis-related pathways in an animal model of T2DM combined with MAFLD.
5.Establishment of prediction model for postoperative delirium in elderly patients with mild stroke undergoing non-cardiac and non-intracranial surgery
Peng SUN ; Caijuan ZHANG ; Jinling YIN ; Xiuhua LI ; Zhaojin JIA
Chinese Journal of Anesthesiology 2024;44(10):1175-1181
Objective:To establish the prediction model for postoperative delirium in elderly patients with mild stroke undergoing non-cardiac and non-intracranial surgery.Methods:This was a nested case-control study. Seven hundred and fifty elderly patients of either sex with mild stroke, aged ≥65 yr, undergoing elective surgical procedures under general anesthesia in the Department of Gastrointestinal Surgery, Orthopedics and Urology at the Tangshan Workers Hospital from May to December 2023, were selected. The perioperative clinical data were collected. The incidence of postoperative delirium was assessed using the Confusion Assessment Scale 1-7 days after surgery or 1 day before discharge. The patients were assigned to the training set and the validation set in a ratio of 7∶3 using a simple random sampling method. Multivariate logistic regression was used to identify the risk factors for postoperative delirium, a postoperative delirium risk prediction model was established based on the risk factors, the nomogram was developed, and the receiver operating characteristic (ROC) curve, calibration curve and decision curve were plotted to assess the accuracy of the prediction model. The prediction model was verified using the validation set, and the calibration curve and ROC curve were plotted to assess the predictive performance of the model.Results:A total of 721 patients were finally included, and 108 patients developed postoperative delirium. Older age, high American Society of Anesthesiologists Physical Status classification, history of preoperative hypertension, short years of education, high preoperative Pittsburgh sleep quality index score, high preoperative National Institutes of Health Stroke Scale score, high intraoperative hypothermia, intraoperative hypotension and high postoperative numerical rating scale score were independent risk factors for postoperative delirium ( P<0.05). The area under the ROC curve of the training set prediction model was 0.996, with a sensitivity of 1.000, and specificity of 0.945. The slope of the calibration curve was close to 1, and the predicted risk of postoperative delirium was in good agreement with the actual risk. When the threshold probability of the decision curve was 0-0.9, the net return rate was higher than the null line. Validation set: In the calibration curve of the prediction model, the cohort and calibration curves were close to the ideal line, with an area under the ROC curve of 0.997, sensitivity of 1.000, and specificity of 0.962. Conclusions:Based on age, American Society of Anesthesiologists Physical Status classification, history of preoperative hypertension, years of education, preoperative Pittsburgh sleep quality index score, National Institutes of Health Stroke Scale score, intraoperative hypothermia and hypotension and postoperative numerical rating scale score, the prediction model for postoperative delirium is developed and has a good predictive performance in elderly patients with mild stroke undergoing non-cardiac and non-intracranial surgery.
6.Optimization of the azomethane oxide and dextran sodium sulfate model of colitis-associated colon cancer and changes in the intestinal microbiota
Dunfang WANG ; Lin ZHU ; Xue FENG ; Caijuan ZHANG ; Haifan LIU ; Yaqing LIU ; Bin LIU ; Li LIU ; Weipeng YANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(2):151-160
Objective To optimize the method of combining azomethane oxide(AOM)and dextran sodium sulfate(DSS)to create a colitis-associated colon cancer(CAC)model,and to explore the pathogenesis of the intestinal flora in CAC.Methods Model groups A and B were established by one and two injections of AOM,respectively,combined with free drinking of DSS,and a normal control group was injected intraperitoneally with normal saline combined with purified water(n=10 mice per group).The better modeling scheme was selected by comprehensive evaluation of the disease activity index score,colon length,tumor rate,and mortality.Serum levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and tumor markers CA199,CEA,and CA724 were detected by enzyme-linked immunosorbent assay.Colon lesions were evaluated by hematoxylin and eosin(HE)staining.Changes in the intestinal microbiota in CAC mice were detected by 16S rDNA high-throughput gene sequencing analysis of mouse feces.Results Both single and enhanced AOM injections combined with DSS induced CAC mice;however,colon growths were larger,more closely arranged,and their morphological size was more consistent in group B compared with group A,with a tumor-formation rate of 100%.IL-6 levels were increased in the model group compared with the normal group(P<0.05).TNF-α levels were increased in the model group compared with the normal group(P>0.05).The CA199 and CEA levels were also significantly increased(P<0.05),but CA724 levels were not.Infiltration of inflammatory cells in the colon detected by HE pathology was accompanied by high-grade intraepithelial tumor-like changes on the surface of the lumen.The diversity and abundance of intestinal bacteria were decreased in CAC mice compared with normal mice:phyla Verrucomicrobiota and Actinobacteriota were significantly increased(P<0.05),Bacteroidota and Campilobacterota were significantly decreased(P<0.05).Akkermansia,Prevotellaceae,Ruminococcus,and Bifidobacterium were significantly increased(P<0.05),and Roseburia,Rikenellaceae_RC9_gut_group,Anaeroplasma,and Muribaculaceae were significantly decreased(P<0.05).Conclusions Two injections of AOM combined with 1.5%(1.5 g/100 mL)DSS induced CAC model mice with a high colon-tumorigenesis rate,uniform tumor morphology,and low mortality,and may thus be the preferred modeling scheme for pharmacodynamic experiments.Disorders or dysfunction of the intestinal flora may lead to increased permeability,loss of intestinal mucosal barrier function,and the release of enterogenic endotoxins,Resultsing in a sustained inflammatory response,as an indirect or direct cause of CAC pathogenesis.
7.Elastase quantitative analysis of elastin effect on mechanical response of anterior cruciate ligament
Wentian ZHANG ; Yuping DENG ; Xiaoyun LIU ; Caijuan LI ; Mian WANG ; Zeyu LIANG ; Liang XIONG ; Gang HUANG ; Guangxin CHEN ; Zitao LI ; Wenhua HUANG
Chinese Journal of Tissue Engineering Research 2024;28(22):3451-3456
BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.
8.Effect of Huangqintang on Inflammation and Short-chain Fatty Acid-related Gut Microbiota in Mouse Model of Inflammation-associated Colorectal Cancer
Lin ZHU ; Dunfang WANG ; Xue FENG ; Caijuan ZHANG ; Haifan LIU ; Yaqing LIU ; Bin LIU ; Li LIU ; Siyuan CHEN ; Weipeng YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):157-169
ObjectiveTo construct a mouse model of inflammation-associated colorectal cancer (CAC) by using azoxymethane (AOM)/dextran sulfate sodium (DSS) and investigate the effect of Huangqintang on the gut microbiota structure of mice during the occurrence and development of CAC by 16S rRNA gene high-throughput sequencing. MethodA total of 225 C57BL/6J mice were randomized into 5 groups (n=45): Normal, model, positive drug (mesalazine), and high (18 g·kg-1) and low (9 g·kg-1)-dose Huangqintang. Except those in the normal group, each mouse was injected with 10 mg·kg-1 AOM on day 1 and day 5 within 1 week and then given 1.5% DSS solution for 7 days, which was then changed to sterile water for 14 days. This process referred to as one cycle, and mice were treated for a total of 3 cycles. On the first day of DSS treatment, mice were administrated with corresponding drugs by gavage, and the normal group and the model group were administrated with pure water by gavage, once a day until the end of the third cycle. The progression of CAC was divided into inflammation, proliferation, and tumorigenesis stages. At the end of each cycle, the body weight and colon length were measured for mice in each group, and the number of colon tumors in mice was recorded. Meanwhile, the disease activity index (DAI) was determined. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and carbohydrate antigen-199 (CA199), a tumor marker in the gastrointestinal tract of mice, were measured by ELISA. Hematoxylin-eosin staining was employed to observe colon lesions. At the same time, 3-5 pellets of fresh feces of mice in the normal group, model group, and high-dose Huangqintang group were collected, from which the fecal DNA of mice was extracted for 16S rRNA gene high-throughput sequencing. ResultCompared with the normal group, the model group showed decreased body weight (P<0.01), increased DAI, and shortened colon length (P<0.05) at the three stages. Compared with the normal group, the model group showed elevated levels of IL-1β, IL-6, and TNF-α (P<0.05) at the proliferation stage and elevated levels of CA199 at the inflammation, proliferation, and tumorigenesis (P<0.01) stages. Compared with the normal group, the model group presented obvious infiltration of inflammatory cells at the inflammation stage, thickening of the muscle layer and abnormal proliferation of mucosal layer cells at the proliferation and tumorigenesis stages, and final formation of advanced intraepithelial tumor lesions. Compared with the model group, the Huangqintang groups showed no significant improvement in the body weight, decreased DAI score, and increased colon length at the three stages, and the increase of colon length in the tumorigenesis stage was significant (P<0.01). At the tumorigenesis stage, the administration of Huangqintang inhibited tumor formation and growth, reduced the number of tumors (P<0.01), lowered the levels of IL-6 (P<0.05, P<0.01), TNF-α (P<0.05, P<0.01), and IL-1β at the three stages, and decreased CA199 at the inflammation stage as well as at the proliferation and tumorigenesis stages (P<0.01, P<0.05). Compared with the model group, the administration of Huangqintang reduced inflammation and abnormal cell proliferation, delaying the occurrence of tumors. Compared with the normal group, the model group showcased decreased alpha and beta diversity and altered structure of gut microbiota at the inflammation, proliferation, and tumorigenesis stages. The administration of Huangqintang adjusted the abundance and diversity of gut microbiota to the normal levels. At the inflammation stage, Huangqintang positively regulated two differential phyla (Firmicutes and Bacteroidetes) and three differential genera (Muribaculaceae, Rikenellaceae_RC9_gut_group, and Flavonifractor) in mice. At the proliferation stage, Huangqintang positively regulated two differential phyla (Bacteroidetes and Patescibacteria) and five differential genera (Muribaculaceae, Rikenellaceae_RC9_gut_group, Candidatus_Saccharimonas, norank_f__UCG-010, and Allobaculum). At the tumorigenesis stage, Huangqintang positively regulated two differential phyla (Proteobacteria and Patescibacteria) and eight differential genera (Muribaculaceae, Candidatus_Saccharimonas, norank_f_UCG-010, Lachnospiraceae_UCG-006, Allobaculum, Bacteroides, Lachnospiraceae_NK4A136_group, and Flavonifractor) in mice. ConclusionHuangqintang can intervene in the AOM/DSS-induced transformation of inflammation to CAC in mice by correcting inflammation and short-chain fatty acid-related microbiota disorders.
9.Mechanism of Sishen Pills-Tongxie Yaofang in the treatment of ulcerative colitis based on network pharmacology and experimental verification
Haifan LIU ; Xue FENG ; Dunfang WANG ; Li LIU ; Yaqing LIU ; Bin LIU ; Lin ZHU ; Caijuan ZHANG ; Weipeng YANG
Science of Traditional Chinese Medicine 2024;2(3):224-236
Background: Ulcerative colitis (UC) is a diffuse nonspecific intestinal inflammation. Spleen-kidney Yang deficiency combined with liver stagnation is the most common symptom. Sishen Pills-Tongxie Yaofang (SSP-TXYF) is a traditional Chinese medicine (TCM) that is widely used in the treatment of this symptom. However, its pharmacological mechanism and active components remain unclear. Objective: This study elucidated the potential mechanism and active components of SSP-TXYF in the treatment of UC from the perspective of TCM syndrome. Methods: Metascape, STRING, and Cytoscape were used to explore the SSP-TXYF-compound-target-UC network and biological enrichment pathways, so as to screen the active compounds, key targets, and pathways of SSP-TXYF. Through the construction of a rat model with UC, the key targets and active components were verified after SSP-TXYF administration. Results: A total of 77 effective active chemical components, 208 potential targets, and 5 core target genes were screened out. Gene Ontology biological process items and Kyoto Encyclopedia of Genes and Genomes signaling pathways showed that SSP-TXYF played a role in regulating nerve-endocrine, cell proliferation and apoptosis, and immune-related pathways. The main compounds and the target protein exhibited a good binding ability in molecular docking. The results of animal experiments showed that SSP-TXYF could improve UC through IL-6, AKT1, PTGS2, CASP3, and JUN, and nobiletin and wogonin were identified as the main active components. Conclusions: This study suggests that nobiletin and wogonin are the main components of SSP-TXYF in the treatment of UC, which provides effective therapeutic targets and drugs for future clinical treatment of UC.
10.Intervention Mechanism of Huangqintang on Intestinal Inflammation and Proliferation in Colitis-associated Colon Cancer
Lin ZHU ; Dunfang WANG ; Xue FENG ; Caijuan ZHANG ; Haifan LIU ; Yaqing LIU ; Bin LIU ; Li LIU ; Weipeng YANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):1-10
ObjectiveTo investigate the efficacy of Huangqintang on mouse models of colitis-associated colon cancer (CAC) and explore the mechanism of Huangqintang in regulating immune function and inflammatory response, inhibiting abnormal cell proliferation, and delaying or inhibiting CAC formation in CAC. MethodC57BL/6J mice were randomly divided into a normal group, model group, mesalazine group, and high- and low-dose Huangqintang groups according to body weight, with 12 mice in each group. Except for the normal group, the rest of the mice were given two intraperitoneal injections of 10 mg·kg-1 azomethane (AOM) and allowed to drink 1.5% dextran sodium sulfate (DSS) freely for seven days and water normally for two weeks. Then, two cycles of ''DSS-drinking water'' were repeated. During the administration of DSS, mice in the normal group and model group were given gavage in equal doses of pure water. Mice in the mesalazine group were given 150 mg·kg-1·d-1 mesalamine suspension for gavage, and mice in the high- and low-dose Huangqintang groups were given 18 and 9 g·kg-1·d-1 Huangqintang for gavage, respectively. Each group was given one dose daily until the end of three cycles. After the intervention, the body weight, colon length, and number of colon tumors in each group were measured, and disease activity index (DAI) scores were performed. The serum contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-10 (IL-10), and gastrointestinal tumor marker carbohydrate antigen-199 (CA199) were detected by enzyme linked immunosorbent assay (ELISA). The colonic lesions were observed by hematoxylin-eosin (HE) staining. The expression of proliferative cell-associated antigen (Ki67) was observed by immunohistochemistry. The expression of T lymphocyte subsets (CD3+, CD4+, CD8+, and CD49b+) in mouse plasma was detected by flow cytometry. Fluorescein isothiocyanate-D (FITC-D) content in mouse serum was detected by fluorescent labeling method. The Western blot method was used to detect the expression of Cyclin D1, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and tightly junction-related Occludin and Claudin-1. ResultCompared with the normal group, the body weight of mice in the model group decreased. DAI score increased significantly, and the colon became shorter. Pro-inflammatory factors such as IL-6, TNF-α, and IL-1β increased, and IL-6 and TNF-α were significantly increased (P<0.05). The inflammatory factor IL-4 (P<0.05) and IL-10 were significantly reduced, and the tumor marker CA199 was significantly increased (P<0.01). HE staining showed that colon lesions, intestinal mucosal epithelial defects with a large number of inflammatory infiltrates, serious crypt structure damage, and glandular arrangement disorder were observed in the model group. Ki67 positive granules were expressed in large areas of colonic tissue. The serum CD4+ and CD4+/CD8+ of mice in the model group decreased significantly (P<0.05), and CD8+ increased significantly (P<0.05). The plasma content of FITC-D in the model group was significantly increased (P<0.05), and the expression of Cyclin D1, CDK2, and CDK4 proteins in colon tissue was significantly increased (P<0.05, P<0.01). In addition, the expression of Occludin and Claudin-1 was significantly decreased. Compared with the model group, the body weight of mice in the mesalazine group and the high- and low-dose Huangqintang groups increased. DAI score decreased, and the colon became longer. IL-6, TNF-α, and IL-1β expression decreased (P<0.05, P<0.01), but there was no significant change in IL-4 and IL-10. The content of CA199 was significantly reduced (P<0.05), and the colomatoid lesions and inflammatory infiltrates were reduced in the mesalazine group and the Huangqintang group. The crypt structure damage was lighter, and the positive expression of Ki67 was reduced. CD4+, CD4+/CD8+, and CD49b+ increased, and the difference was not statistically significant. FITC-D content decreased (P<0.05). The expression of Cyclin D1, CDK2, and CDK4 decreased (P<0.05, P<0.01), and Claudin-1 and Occludin protein expression increased in the high-dose Huangqintang group (P<0.05). ConclusionHuangqintang has a certain delay and inhibitory effect on AOM/DSS-induced inflammatory cancer transformation, and its mechanism of action may be related to regulating immune function and inflammatory response, inhibiting the release of pro-inflammatory factors, repairing damaged intestinal barriers, inhibiting abnormal proliferation of colon cells, and intervening in the formation and development of CAC colon tumors.

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