1.Regulatory Effect of Huangqin Tang on Metabolic Homeostasis During Colitis-cancer Transformation in Colitis-associated Colorectal Cancer
Xingbo ZUO ; Xue FENG ; Caijuan ZHANG ; Haifan LIU ; Jianyao LIU ; Bin LIU ; Lin ZHU ; Qiyue SUN ; Dunfang WANG ; Weipeng YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):21-28
ObjectiveTo investigate the mechanism of Huangqin Tang (HQT) in regulating metabolic reprogramming during the inflammation-cancer transformation in colitis-associated colorectal cancer (CAC). MethodsCAC mouse model was established using the carcinogen azoxymethane (AOM) combined with the inflammatory agent dextran sulfate sodium (DSS). HQT treatment was adopted. Serum metabolomics analysis was performed at three stages (inflammation, proliferation, and tumor formation) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) untargeted metabolomics coupled with multivariate statistical analysis to explore the mechanism of HQT intervention in metabolism in CAC. ResultsThe results revealed that HQT significantly reversed the disturbance of key metabolites in CAC mice. A total of 52, 67, and 45 differential metabolites were identified in the model group, compared to the normal group, during inflammation, proliferation, and tumor stages, respectively. Lactate, linoleic acid, oleic acid, elaidic acid, and betaine were characteristic metabolites persistently enriched throughout colitis-cancer transformation. Pathway enrichment analysis of differential metabolites showed that linoleic acid metabolism and arachidonic acid metabolism were the most significantly disturbed in CAC pathogenesis. The proliferation stage featured expanded amino acid metabolic networks, while the tumor stage uniquely exhibited two new pathways of nicotinate and nicotinamide metabolism and phosphoinositide metabolism. HQT exerted stage-specific regulatory effects: targeting arachidonic acid metabolism in the inflammation stage, correcting the dysregulation of choline-carnitine metabolism in the proliferation stage, and rescuing nicotinamide and tryptophan metabolic collapse in the tumor stage. ConclusionHQT exerts regulatory effects on metabolic disorders at various stages of the colitis-cancer transformation process, thereby effectively slowing the progression from colitis to cancer. The study also reveals the dynamic metabolic characteristics of colorectal "inflammation-cancer transformation,"providing new insights for research on the targeted mechanisms of traditional Chinese medicine in anti-tumor therapy based on metabolic reprogramming.
2.Sishenwan Combined with Tongxie Yaofang Treats Ulcerative Colitis with Spleen-kidney Yang Deficiency and Liver Depression
Yaqing LIU ; Haifan LIU ; Bin LIU ; Xue FENG ; Caijuan ZHANG ; Dunfang WANG ; Lin ZHU ; Weipeng YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):40-48
ObjectiveTo induce the rat model of ulcerative colitis (UC) with spleen-kidney Yang deficiency and liver depression, and explore the efficacy and mechanism of Sishenwan combined with Tongxie Yaofang (SSW&TXYF) based on the therapeutic principles of tonifying spleen, soothing liver, warming kidney, and astringing intestine. MethodSixty male SD rats were randomized into normal, model, mesalazine, and high-, medium-, and low-dose SSW&TXYF groups. The rats in other groups except the normal group were administrated with Sennae Folium decoction and hydrocortisone and received tail clamping for 14 days. On day 14, rats received enema with TNBS-ethanol solution to induce UC. The rats were administrated with corresponding drugs from day 15 of modeling, and the body weight and mental state were observed and recorded. The sucrose preference test was performed from day 25. On day 28, the rectal temperature was measured, and the rats were administrated with 3% D-xylose solution at a dose of 10 mL·kg-1 by gavage. Blood was sampled 1 h later, from which the serum was collected for measurement of the D-xylose content. The serum, hippocampus, and colorectum samples of rats were collected on day 29. The levels of gastrin (GAS), adrenocorticotropic hormone (ACTH), corticosterone (CORT), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), interleukin (IL)-4, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the serum and 5-hydroxytryptamine (5-HT) in the hippocampus were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the colonic lesions. The mRNA and protein levels of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in the colon tissue were determined by Real-time PCR and Western blot, respectively. ResultCompared with the normal group, the model group showed decreased body weight, anal temperature, and D-xylose content in the serum and increased GAS content (P<0.01). The modeling led to cAMP/cGMP unbalance and decreased the ACTH and CORT content in the serum (P<0.01), the preference for sucrose water, and the 5-HT content in the hippocampus (P<0.01). Moreover, it shortened the colorectal length and caused massive infiltration of inflammatory cells and severe structural damage in the colon tissue. High, medium, and low doses of SSW&TXYF improved above indicators (P<0.05, P<0.01), reduced inflammatory infiltration, and repaired the pathological damage of the tissue. Compared with the normal group, the model group showed lowered IL-4 level (P<0.01) and elevated TNF-α and IFN-γ levels (P<0.05, P<0.01) in the serum, as well as up-regulated expression of p38 MAPK, ERK, and JNK (P<0.05, P<0.01). Compared with the model group, SSW&TXYF elevated the IL-4 level (P<0.01), lowered the TNF-α and IFN-γ levels (P<0.05, P<0.01), and down-regulated the mRNA and protein levels of p38 MAPK, ERK, and JNK (P<0.05, P<0.01). ConclusionA rat model of UC with spleen-kidney Yang deficiency and liver depression was successfully established. SSW&TXYF can significantly mitigate this syndrome by reducing the inflammatory response in the colon and inhibiting the MAPK pathway.
3.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.
4.Correlation of KRAS Gene 3'UTR Polymorphisms with Cervical Cancer and Cervical Intraepithelial Neoplasia in Chinese Han Population in Yunnan Province
Ni GUO ; Cheng ZHANG ; Chao HONG ; Weipeng LIU ; Yufeng YAO ; Zhiling YAN
Journal of Kunming Medical University 2024;45(2):14-22
Objective To investigate the correlation between rs712 and rs7973450 located at the 3'UTR region of the KRAS gene and the risk of cervical cancer(CC)and cervical intraepithelial neoplasia(CIN)in Chinese Han population in Yunnan province.Methods A total of 2405 individuals(461 subjects with CIN,961 subjects with CC and 983 healthy controls)were enrolled.The SNPs were genotyped used TaqMan assay and the correlation of these SNPs with CIN and CC was analyzed.Results The A allele of rs7973450 might be a protective factor for the occurrence of CIN(P = 0.004,OR= 0.651,95%CI 0.487~0.871)and CC(P = 7.00×10-4,OR= 0.667,95%CI 0.529~0.844).There was no significant difference in allelic and genotypic distribution of rs712 among CIN,CC and Control groups(P>0.017).The haplotype assay showed thatrs712A-rs7973450G was associated with increased risk of CIN(P = 4.00×10-4;OR= 1.714,95%CI 1.269~2.314)and CC(P = 3.84×10-5,OR= 1.667,95%CI 1.305~2.131).While haplotype rs712A-rs7973450A was associated with a lower risk of CC(P = 0.012,OR= 0.790,95%CI 0.658~0.950).Conclusion The A allele of rs7973450 in 3'UTR of KRAS gene might be the protective factor for the occurrence of CIN and CC in a Chinese Han population in Yunnan province.
5.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.
6.The characteristics and influencing factors of medicine cost for orthopedic surgery patients in hospitals of Shanxi province
Weipeng LI ; Nan SHANG ; Zhiqi ZHANG ; Yun LI ; Xiaojun ZHENG
China Pharmacy 2024;35(5):612-617
OBJECTIVE To analyze the characteristics and influencing factors of medicine cost for orthopedic surgery patients in Shanxi province, and to provide reference for the rational management of medicine cost in orthopedic surgery patients. METHODS A retrospective analysis was conducted on the case information of 584 204 orthopedic surgery patients in Shanxi province from 2016 to 2021. Medicine cost was analyzed by year, region, hospital level, type of surgery and type of surgical incision. Single factor analysis and generalized linear regression model were used to analyze the influencing factors of total medicine cost, and structural equation model was used for verification. RESULTS The research findings indicated that joint replacement surgery (42.61%) and post-fracture external fixation surgery (12.60%) were the most common types of procedures. There was statistical significance in medicine cost for different surgical types among different regions and hospital levels (P<0.05). In the Jinzhong region, the total medicine cost for post-fracture external fixation surgery was the highest ([ 11 719.97±4 374.73) yuan], while in tertiary grade A hospitals, the total medicine cost for post-fracture external fixation surgery was also the highest ([ 13 584.71±4 531.82) yuan]. Among class Ⅰ incision surgeries, the cost of antibiotics for post-fracture external fixation surgery was the highest ([ 1 176.25±341.42) yuan]. Generalized linear regression model revealed that hospital location, hospital level, gender, payment method, length of hospital stays, and surgical type were the independent influencing factors for total medicine cost (P<0.05). Structural equation model further disclosed that hospital level, payment type, and surgical type had significant effects on total medicine cost (P<0.05). CONCLUSIONS Attention should be paid to the high cost of antibiotics for class Ⅰ incision surgery, and further research on their rational use should be conducted.
7.Prognostic factors analysis of YL-1 type hard channel trepanation and drainage combined with stereotactic therapy for hypertensive intracerebral hemorrhage
Bin LIU ; Lei DING ; Weipeng CHENG ; Pengkun FAN ; Yan WANG ; Bing ZHANG ; Chao REN ; Xiuyao MA
Journal of Clinical Surgery 2024;32(11):1142-1146
Objective To explore the clinical efficacy and prognostic factors of YL-1 type hard channel trepanation and drainage combined with stereotactic treatment for hypertensive intracerebral hemorrhage.Methods A retrospective study was conducted on 110 patients with hypertensive intracerebral hemorrhage at the Cerebrovascular Disease Center of the First People's Hospital of Suzhou from August 2019 to October 2022.The observation group(55 cases)received YL-1 type hard channel drilling and drainage combined with stereotactic treatment,while the control group(55 cases)received simple YL-1 type hard channel drilling and drainage.The perioperative indicators,neurological damage,and prognosis of the two groups of patients were compared;Using multiple Logistic regression analysis to identify the prognostic factors affecting patients.Results The perioperative indicators,neurological damage,and prognosis of the observation group were better than those of the control group(P<0.05);The admission NIHSS score(OR=2.504,P<0.05),simple minimally invasive drilling and drainage(OR=1.881,P<0.05),disease duration>24 hours(OR=2.782,P<0.001),and ventricular rupture(OR=2.252,P<0.05)are risk factors for poor prognosis in patients.Conclusion The prolongation of the patient's disease course,ventricular rupture,and severe neurological damage are associated with poor prognosis.Combining stereotactic minimally invasive surgery has a positive significance for improving the prognosis of patients with cerebral hemorrhage.
8.Lung protection and mechanism of total flavonoids from Patrina villosa Juss in an experimental model of acute lung injury in rats
Jianbo LI ; Haiying FENG ; Jie ZHANG ; Ming LIU ; Haibo JIA ; Weipeng ZHAO
Chinese Journal of Pathophysiology 2024;40(7):1230-1236
AIM:To investigate the protective effect of total flavonoids from Patrina villosa Juss(PJF)on the lung in an experimental rat model of acute lung injury(ALI),and to elucidate the potential mechanism.METHODS:The ALI rat model was established by instilling 5 mg/kg of lipopolysaccharide(LPS)into the airway.Sixty male SD rats were randomly divided into 4 groups:control,LPS,LPS+low-dose PJF(receiving 100 mg/kg PJF one hour before ALI modeling)and LPS+high-dose PJF(receiving 300 mg/kg PJF one hour before ALI modeling).Each group consisted of 15 animals.Lung tissues and bronchoalveolar lavage fluid(BALF)were collected from all groups 24 h after modeling.For as-sessment of lung tissue morphology,HE staining was performed.The wet/dry weight ratio of the lung tissue was deter-mined using the wet/dry weighing method.Evans blue staining was conducted to assess epithelial barrier permeability in lung tissues.ELISA was used to detect the levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in the BALF,as well as oxidative stress markers including superoxide dismutase(SOD),myeloperoxi-dase(MPO)and glutathione peroxidase(GSH-Px)activity,and malondialdehyde(MDA)content in the lung tissue.The expression levels of C/EBP homologous protein(CHOP),glucose-regulated protein 78(GRP78)and X-box binding pro-tein 1(XBP1)in the lung tissue were analyzed by Western blotting.RESULTS:Compared with control group,the rats in LPS group exhibited a blurred alveolar structure with a significant infiltration of inflammatory cells.The ALI score and the wet/dry weight ratio of the lung tissue were increased(P<0.05).Concurrently,the levels of IL-6,IL-1β and TNF-α in the BALF,along with MDA content and MPO activity in the lung tissue,were elevated(P<0.05).Additionally,the pro-tein levels of CHOP,GRP78 and XBP1 were up-regulated in the lung tissue(P<0.05),while the SOD and GSH-Px activi-ty was significantly decreased(P<0.05).Compared with LPS group,PJF intervention exerted beneficial effects on the lung tissue morphology with reduced ALI score and lower lung wet/dry weight ratio(P<0.05).Moreover,the levels of IL-6,IL-1β and TNF-α in BALF,as well as MDA content,MPO activity and the protein levels of CHOP,GRP78 and XBP1 in the lung tissue were all significantly decreased(P<0.05),while the SOD and GSH-Px activity was significantly in-creased(P<0.05).The efficacy in high-dose group exceeded that in low-dose group.CONCLUSION:The PJF have pro-tective effect on the lungs of rats with ALI,and its mechanism may be related to the inhibition of inflammation,oxidative stress and endoplasmic reticulum stress.
9.Research progress on the therapeutic effect and mechanism of Xiaoxuming decoction on nervous system diseases
Xuan LIU ; Huiling HOU ; Weipeng SONG ; Xiaoming LI ; Yang LIU ; Wei ZHANG ; Xiwu ZHANG ; Weiming ZHAO
China Pharmacist 2024;28(11):536-549
Xiaoxuming decoction is one of the classical prescriptions in ancient times,mainly used for treating stroke syndrome,with significant therapeutic effects.Recent studies have found that it is also effective for other neurological diseases besides stroke,such as facial paralysis and vertigo,but there are few reports on related achievements,lacking systematic organization and summary.This article systematically summarizes the application practice and mechanism of Xiaoxuming decoction in the above-mentioned diseases,aiming to provide a solid foundation and scientific reference for deepening the exploration of Xiaoxuming decoction in the field of nervous system disease.
10.An exploratory study of the domestic robotic surgical system for general surgery
Jing YANG ; Zeping ZHANG ; Guoyuan YANG ; Yiyun PENG ; Meijuan SONG ; Weipeng ZHAN ; Hongwei TIAN ; Ming HU ; Changfeng MIAO ; Dongdong CHEN ; Wei FANG ; Wutang JING ; Yuntao MA
Chinese Journal of General Surgery 2024;39(9):698-702
Objective:To evaluate the safety and efficacy of the domestic robotic surgical system for general surgery.Methods:A prospective single-center, single-arm exploratory study was conducted at Gansu Provincial People's Hospital from Jun 2022 to Oct 2023, enrolling 54 patients undergoing general surgery using domestically produced Toumai? Endoscopic Surgical Robotic System. The primary study endpoint was surgical success rate, and the secondary study endpoints were intraoperative bleeding, operative time, complications, system performance, hospitalization days.Results:In this study, robotic surgery was successfully completed in 52 patients, and in 2 patients undergoing thyroid operation it was converted to open surgery due to bleeding, with a success rate of 96%, no organ injury or death during surgery, and no system failure. The types of surgery included cholecystectomy, radical gastric cancer resection, radical colorectal cancer resection, inguinal hernia repair, partial hepatectomy, total thyroidectomy and choledocho-jejunal anastomosis.Conclusion:The study provides preliminary evidence of the safety and efficacy of the Toumai? Endoscopic Surgical Robotic System for the treatment of general surgical diseases.

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