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.Xiao Chaihutang Intervention in Digestive System Tumors: A Review
Ying WANG ; Tonghui JIN ; Yanting SUN ; Tiejun LIU ; Weipeng YANG ; Han WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):257-268
Xiao Chaihutang, originating from the Treatise on Typhoid and Miscellaneous Diseases, is a classic formula for harmonizing the Shaoyang. It excels in regulating the pivotal mechanism and unblocking the triple energizer, corresponding to the pathogenesis of digestive system tumors characterized by the interlocking of deficiency, stasis, phlegm, and toxicity, as well as disharmony between Yin and Yang. This paper systematically reviews research findings from China and abroad over the past decade, exploring the anti-tumor effects of Xiao Chaihutang on digestive system tumors from three dimensions: theoretical rationale, clinical efficacy, and molecular mechanisms. At the level of principle and method, Xiao Chaihutang takes "harmonization" as its core therapeutic guideline. By reconciling the exterior and interior to restore the Shaoyang pivot, harmonizing Yin and Yang to improve the tumor microenvironment, and regulating the liver and spleen to consolidate and protect the foundation of postnatal essence, it promotes the restoration of the body's dynamic balance of Yin and Yang. Clinical studies have demonstrated that Xiao Chaihutang, used alone or in combination with modern medical therapies, shows definite efficacy against digestive system tumors such as hepatocellular carcinoma, pancreatic carcinoma, and gastrointestinal carcinoma. It can significantly improve patients' quality of life, inhibit tumor progression, effectively relieve concomitant symptoms such a s cancer-related fever, anxiety, depression, and insomnia, and alleviate postoperative embolic syndromes as well as adverse reactions to radiotherapy and chemotherapy. Experimental studies have revealed that Xiao Chaihutang can inhibit tumor cell proliferation, induce apoptosis, arrest the cell cycle, suppress tumor cell invasion and metastasis, and improve the tumor microenvironment. Through the above analysis, this study elucidates the current clinical and experimental research status of Xiao Chaihutang in the treatment of digestive system tumors, aiming to provide theoretical support for its precise clinical application. On this basis, it further explores key issues in the identification of pharmacodynamic substances and the accumulation of evidence in evidence-based medicine, thereby offering a new perspective for the innovative development of integrative Chinese and Western medicine in synergistic cancer therapy.
3.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.
4.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.
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.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.
7.Robotic-assisted"3+1"Surgical Mode Strategy for 6 Cases of Median Arcuate Ligament Syndrome
Yuqi MA ; Yuntao MA ; Diaolong MA ; Qian YANG ; Weipeng ZHAI ; Hui CAI ; Ming HU
Chinese Journal of Minimally Invasive Surgery 2024;24(10):678-682
Objective To investigate the feasibility of robotic-assisted"3+1"surgical mode strategy for the treatment of median arcuate ligament syndrome(MALS).Methods Six patients diagnosed as MALS were enrolled between June 2019 and October 2023.The utilization of robotic-assisted"3+1"surgical mode(a 4-hole operation with 3 robot arms and 1 assistance hole)was carried out.Through a posterior splenic artery approach,the compression of the midline arcuate ligament on the abdominal trunk was relieved,which was an abdominal trunk vascularization.Results All the 6 patients underwent robotic-assisted"3+1"surgical mode successfully.The surgical duration(including the time for connecting and disconnecting the machine)was 38-52 min,with a mean of 43.2 min.The intraoperative bleeding volume was 5-25 ml,with a mean of 15 ml.The postoperative hospital stay was 6-9 d,with a mean of 7.5 d.All the 6 patients were followed up for 1-45 months after surgery(median,2.5 months).One patient remained unchanged in body weight,while 5 patients gained 1.0-2.0 kg in body weight,with a mean of 1.5 kg.The symptom of postprandial epigastric pain completely resolved in 5 patients,while the symptom was reduced but not completely alleviated in one patient.Conclusion Treatment of MALS with the robotic-assisted"3+1"surgical model involving abdominal trunk vascularization through a posterior splenic artery approach is safe and feasible.
8.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.
9.Surgical treatment of isolated pulmonary mucormycosis
Weipeng ZHU ; Fan YANG ; Jiashun CAO ; Xianming HOU ; Ting ZHOU ; Zimu ZHANG ; Donghong CHEN
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(10):612-617
Objective:To retrospectively analyze the surgical treatment of isolated pulmonary mucormycosis, explore the timing and effect of operation.Methods:Clinical data of patients with isolated pulmonary mucormycosis who underwent surgical treatment from April 2019 to April 2024 were collected and retrospectively analyzed, combined with literature review.Results:The clinical data of 13 patients with pulmonary mucormycosis who underwent operation were collected, including 9 males and 4 females, aged 22~64(45.4±15.4)years old. The basic diseases included diabetes mellitus in 10 cases and hematological malignancy in 3 cases. Seven patients had hemoptysis during the course of the disease. All 13 patients received adequate antifungal therapy before surgery, and 12 patients received bronchoscopic interventional therapy. Ten patients underwent lobectomy, two underwent pneumonectomy, and one underwent a right sleeve pneumonectomy. All patients were cured except one patient with bronchopleural fistula after operation. All patients achieved complete elimination of mucor and also discontinuation of antifungal drug.Conclusion:For isolated pulmonary mucormycosis, on the basis of systemic antifungal treatment, actively seek the opportunity of surgical intervention, can shorten the course of the disease and achieve good therapeutic results.
10.Efficiency of large language models in answering questions about childhood asthma
Weipeng HAN ; Xiaomei YIN ; Jian WANG ; Xuejun LI ; Jijiang YANG
Journal of Clinical Medicine in Practice 2024;28(11):6-11
Objective To evaluate the performance of large language models in answering questions about childhood asthma, comprehensively understand the quality of their provision of information on children's health, and identify their limitations to facilitate model improvement. Methods Sixty common questions related to childhood asthma were formulated and put to two large language models known as Wenxin Yiyan and Zhipu Qingyan, which were publicly available in China. Three pediatric asthma specialists assessed the quality of the large language models'responses by using a blind method. Results Wenxin Yiyan scored higher in terms of accuracy, understanding, reliability, and logicality; Zhipu Qingyan scored higher in term of safety. Comparing the scores of the five different dimensions, it was found that large language models scored higher in terms of understanding, reliability and logicality, but relatively insufficient in terms of accuracy and safety. Conclusion Application of large language models in the education of children with asthma can provide useful references for asthma children and their parents. However, the current large language model technology still has certain limitations in terms of accuracy and safety, which requires further improvement and optimization.


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