BACKGROUND:Ammonia poisoning is considered to be the main hypothesis for the pathogenesis of hepatic encephalopathy.Ammonia can lead to psychiatric and cognitive behavioral disorders,although the specific pathological molecular mechanisms remain unclear.OBJECTIVE:To investigate the effects of ammonia poisoning on cognitive behavior and hippocampal neuronal synapses in mice.METHODS:Thirty-two C57BL/6J mice were randomly divided into a normal control group and an ammonium chloride group,with 16 mice in each group.Normal saline was injected intraperitoneally in the control group,and ammonium chloride(10 mmol/kg)was injected intraperitoneally in the ammonium chloride group to construct a model of ammonia poisoning,once a day.After 7 days of ammonium chloride intervention,blood samples were collected from the hearts of six mice in each group for blood ammonia concentration detection.Behavioral experiments,including the open field test,novel object recognition test,and Y-maze test,were performed to assess mental and cognitive-behavioral changes in mice.Finally,hippocampal tissues were extracted for western blot analysis to detect the expression levels of synaptophysin and postsynaptic density protein-95 in hippocampal neurons.RESULTS AND CONCLUSION:The blood ammonia concentration was significantly elevated in the ammonium chloride group compared with the control group(P＜0.05).Mice in the ammonium chloride group showed anxiety-like behavior and disinhibition phenomenon,and a significant decrease in recognition memory and working memory ability.Western blot results revealed that the expression of synaptophysin and postsynaptic density protein-95 protein in hippocampal neurons in the ammonium chloride group was lower than that in the control group(P＜0.05).To conclude,ammonia poisoning can induce hippocampal neuronal synaptic damage,leading to psychiatric and cognitive behavioral abnormalities in mice.

ObjectiveTo integrate network pharmacology prediction with multi-level experimental verification methods， and to explore in depth the therapeutic efficacy and potential mechanism of luteolin in treating gout. MethodsDatabases were used to obtain potential pharmacodynamic targets of luteolin. Protein-protein interaction （PPI） network construction and network pharmacology analysis techniques were used to screen key core targets of luteolin in gout treatment. Further biological function enrichment analysis and signaling pathway analysis were performed on these targets. Molecular docking simulation was used to calculate the binding energy between luteolin and potential core targets， clarifying the strength of their interactions. In the in vivo experiment for hyperuricemia， 48 mice were randomly divided into a blank group， a model group， an allopurinol group （5 mg·kg^-1）， and low-dose （10 mg·kg^-1）， medium-dose （30 mg·kg^-1）， and high-dose （90 mg·kg^-1） luteolin groups. For the first three days， the blank and model groups were gavaged with an equal volume of normal saline， while the allopurinol group and luteolin groups were gavaged with corresponding drugs. From day 4 onwards， modeling was performed by intraperitoneal injection at 12：00 daily （normal saline for the blank group， and oxonic acid potassium-hypoxanthine mixture for other groups， with 300 mg·kg^-1 for each group）. Gavage intervention was administered at 18：00 daily （normal saline for the blank/model groups， and corresponding drugs for the treatment groups） until day 7. After sampling， levels of serum uric acid （UA）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were measured. Levels of xanthine oxidase （XO） in the liver and kidney， ATP-binding cassette transporter G2 （ABCG2） and malondialdehyde （MDA） in the kidney， and superoxide dismutase （SOD） in the liver were determined. Renal HE staining was also performed. In the pharmacodynamic study of gouty arthritis， 36 rats were randomly divided into a blank group， a model group， a colchicine group （0.315 mg·kg^-1）， and low-dose （7 mg·kg^-1）， medium-dose （21 mg·kg^-1）， and high-dose （63 mg·kg^-1） luteolin groups. The model was established by vertically injecting 100 µL of 25 g·L^-1 monosodium urate suspension into the posterior lateral aspect of the right ankle joint （the blank group was injected with an equal volume of normal saline）， with repeated injections every two days for reinforcement. From day 2 after modeling， daily gavage administration was performed （normal saline for the blank/model groups， and corresponding drugs for the treatment groups） for a total of 16 days. During the experiment， ankle swelling and pain threshold were measured regularly. After sampling， levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） were determined. Ankle joints were subjected to HE， Masson， and safranin O-fast green staining， and HE staining was also performed on ankle synovial tissue and various organs. Western blot was used to determine the expression levels of key proteins in gout-related signaling pathways. ResultsNetwork pharmacology analysis predicted that luteolin may regulate over 20 core targets， such as XO， ABCG2， nuclear factor erythroid 2-related factor 2 （Nrf2）， and SOD， through acting on signaling pathways including NF-κB， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， and ABC transporters， thereby affecting uric acid metabolism and inflammatory responses. In the hyperuricemia model， compared with the blank group， the model group showed significantly increased serum UA level， liver and kidney XO activity， renal ABCG2 expression， and liver SOD activity （P<0.01）. Compared with the model group， the high-dose luteolin group significantly reduced serum UA level （P<0.01）， inhibited liver and kidney XO activity （P<0.01）， and significantly increased renal ABCG2 expression and liver SOD activity （P<0.01）， effectively alleviating renal oxidative stress damage and improving renal histopathological status. In the gouty arthritis model， compared with the blank group， the model group showed significant ankle swelling， decreased pain threshold， and significantly increased levels of IL-6， IL-1β， and TNF-α in serum and synovial tissue （P<0.01）. The high-dose luteolin group significantly reduced ankle swelling， prolonged hot plate pain threshold， effectively decreased the levels of the above inflammatory factors in serum and synovial tissue （P<0.01）， and significantly improved ankle pathological damage， showing good analgesic and anti-inflammatory effects. Western blot results further confirmed that luteolin significantly upregulated Nrf2 protein expression and downregulated XO and nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） expression in animals. ConclusionLuteolin can improve symptoms of hyperuricemia and gouty arthritis， and its potential mechanism may be related to inhibiting XO activity， increasing ABCG2 and SOD levels， and regulating Nrf2-mediated oxidative stress-related pathways.

Objective To investigate the relationship between symptom burden and nutritional status under Traditional Chinese Medicine (TCM) constitution classification in patients undergoing chemotherapy. Methods Data on the physical constitution, symptom burden, and nutritional status of 640 patients with malignant tumors within the 21st–28th days of chemotherapy treatment were collected and analyzed. Results Symptom burden was found to have a positive correlation with nutritional risk and TCM bias (except for idiosyncrasies), suggesting that constitution bias may be an important internal factor for the aggravation of clinical symptoms and malnutrition in patients with cancer. Conclusion The relationship between symptom burden and nutritional status in chemotherapy under the guidance of TCM constitution can be studied to predict the nutritional status and symptom burden of patients after chemotherapy to guide the symptom and nutritional management of patients with cancer in the chemotherapy stage.

ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

BACKGROUND:Ammonia poisoning is considered to be the main hypothesis for the pathogenesis of hepatic encephalopathy.Ammonia can lead to psychiatric and cognitive behavioral disorders,although the specific pathological molecular mechanisms remain unclear.OBJECTIVE:To investigate the effects of ammonia poisoning on cognitive behavior and hippocampal neuronal synapses in mice.METHODS:Thirty-two C57BL/6J mice were randomly divided into a normal control group and an ammonium chloride group,with 16 mice in each group.Normal saline was injected intraperitoneally in the control group,and ammonium chloride(10 mmol/kg)was injected intraperitoneally in the ammonium chloride group to construct a model of ammonia poisoning,once a day.After 7 days of ammonium chloride intervention,blood samples were collected from the hearts of six mice in each group for blood ammonia concentration detection.Behavioral experiments,including the open field test,novel object recognition test,and Y-maze test,were performed to assess mental and cognitive-behavioral changes in mice.Finally,hippocampal tissues were extracted for western blot analysis to detect the expression levels of synaptophysin and postsynaptic density protein-95 in hippocampal neurons.RESULTS AND CONCLUSION:The blood ammonia concentration was significantly elevated in the ammonium chloride group compared with the control group(P＜0.05).Mice in the ammonium chloride group showed anxiety-like behavior and disinhibition phenomenon,and a significant decrease in recognition memory and working memory ability.Western blot results revealed that the expression of synaptophysin and postsynaptic density protein-95 protein in hippocampal neurons in the ammonium chloride group was lower than that in the control group(P＜0.05).To conclude,ammonia poisoning can induce hippocampal neuronal synaptic damage,leading to psychiatric and cognitive behavioral abnormalities in mice.

Colorectal cancer has an insidious onset， and some patients have already developed local invasion or metastasis at the time of diagnosis， which affects treatment strategy selection and survival prognosis. The tumor microenvironment is not only the basic condition for tumor cell survival but also the core regulatory factor driving their local invasion and distant metastasis. This article reviewed the mechanisms by which traditional Chinese medicine regulates the tumor microenvironment to inhibit colorectal cancer metastasis. It was found that traditional Chinese medicine active ingredients such as astragalus polysaccharides， leonurine， kaempferol， etc.， as well as traditional Chinese medicine formulas such as Jianpi jiedu formula， can inhibit colorectal cancer metastasis by regulating key links of the tumor microenvironment， including immunosuppression， inflammatory response， intestinal microecological disorder， abnormal angiogenesis， and extracellular matrix homeostasis imbalance. However， current related research was still mainly based on cell and animal experiments， with limited clinical evidence-based data， and mechanistic studies mostly focued on single signaling pathways. Future research should integrate multi-omics technologies and systems biology methods to systematically elucidate the key targets and action networks through which traditional Chinese medicine regulates the colorectal cancer tumor microenvironment to combat metastasis.

Purpose To explore the characteristics of gray matter(GM)volume changes in migraine patients using 7T MRI and voxel-based morphometry(VBM).Materials and Methods This prospective study enrolled 30 migraine patients and 41 age-and gender-matched healthy controls from Beijing Tiantan Hospital,Capital Medical University between November 2023 and November 2024.All participants underwent 7T MRI with 3D T1-weighted magnetization-prepared two rapid gradient-echo(MP2RAGE)sequences for structural brain imaging.VBM analysis was performed to quantify GM,white matter,cerebrospinal fluid and total brain volumes,followed by calculations of their relative percentages.The difference in GM volume between the two groups was compared to identify brain regions with characteristic GM volume changes in migraine patients.And the correlation between these characteristic GM volume alterations and clinical scales was analyzed.Results Migraine patients exhibited significantly lower total GM volume compared to healthy controls(t=2.096,P=0.040),while no group differences were observed in white matter or cerebrospinal fluid volumes(t=0.980,0.151;P=0.330,0.880).VBM analysis revealed reduced GM volume in the left orbitofrontal cortex(t=4.301,P=0.022),left hippocampus(t=5.226,P=0.006)and left parahippocampal gyrus(t=3.960,P=0.040)in the migraine group.Negative correlations were identified between:left orbitofrontal cortex GM volume and headache duration(r=-0.506,P=0.008),left hippocampal GM volume and patient health questionnaire-9 scores(r=-0.620,P=0.003),and left parahippocampal GM volume and visual analogue scale scores(r=-0.449,P=0.019).Conclusion VBM analysis based on 7T MP2RAGE data demonstrates characteristic GM volume reductions in the left orbitofrontal cortex,left hippocampus and left parahippocampal gyrus in migraine patients,with these structural alterations significantly correlate with depressive symptoms and headache burden.The observed microstructural abnormalities may reflect underlying pathophysiological mechanisms related to pain processing,emotional regulation and long-term disease burden in migraine.

Objective To explore the efficacy of artificial tiger bone powder in the treatment of knee osteoarthritis(KOA)through Wnt/β-catenin pathway.Methods Forty SD rats were divided into control group,KOA group,low-dose group and high-dose group.The KOA group,low-dose group and high-dose group were all modeled by anterior cruciate ligament transection.After modeling,high-dose and low-dose groups were treated with artificial tiger bone powder at a dose of 10g/kg and 5g/kg orally respectively.Cartilage tissue specimens of rats in each group were collected for hematoxylin-eosin staining and immunohistochemical staining,and Mankin score was conducted.The cartilage tissues of the knee joints of normal SD rats were taken for primary chondrocyte culture.After passage,they were divided into blank group(without any stimulation),interleukin-1β(IL-1β)group(incubated with 10ng/ml IL-1β for 1 day),and IL-1β+artificial tiger bone powder group(incubated with 10ng/ml IL-1β and 10μg/ml artificial tiger bone powder for 1 day).Detect the activities of related substances such as typeⅡ collagen(Col Ⅱ),matrix metalloproteinase-13(MMP-13),and β-catenin in each group.Results Compared with KOA group,after artificial tiger bone powder treatment,the degree of redness and swelling of the knee joints in rats was reduced,the range of joint motion was significantly improved,and the levels of inflammatory factors were decreased.Compared with the IL-1β group,the expression levels of Col Ⅱ protein and mRNA in IL-1β+artificial tiger bone powder group were significantly increased(P＜0.05),while the expression levels of MMP-13,β-catenin protein and mRNA decreased significantly(P＜0.05).After adding the Wnt agonist LiCL,the mRNA expression levels of Wnt1,β-catenin and MMP-13 increased,while the addition of the Wnt inhibitor WIF1 could reduce the mRNA expression levels of Wnt1,β-catenin and MMP-13.Conclusion Artificial tiger bone powder can inhibit the progression of KOA by regulating Wnt/β-catenin pathway.

This paper aims to discuss the application value and progress of artificial intelligence (AI) in the diagnosis and treatment of gastrointestinal tumors and teaching practice of gastrointestinal oncology. Through a comprehensive analysis of the current clinical research status and literature, this paper summarizes the application practice and exploratory thinking of AI and deep learning technologies in gastrointestinal oncology. In diagnosis, AI technologies have improved the early detection and diagnosis efficiency for gastrointestinal tumors by optimizing medical image analysis, especially in the recognition of liver metastases. Applications of AI in pathological diagnosis include automatic recognition of tumor cells and tissue structure, as well as improving diagnostic sensitivity and specificity through feature extraction and pattern recognition. In treatment, the application scenarios of AI include rapid diagnosis, accurate staging, personalized treatment plan formulation, drug development, and surgical assistance. In surgical assistance, AI technology improves the safety and effectiveness of surgery through preoperative evaluation, surgical navigation, and postoperative evaluation. In teaching, AI technology facilitates knowledge acquisition and clinical skill enhancement of medical students by providing a multidisciplinary learning platform, simulating clinical environment and case details, and establishing a remote learning platform. The application of AI technology in teaching also includes deep learning and assessment feedback, providing personalized teaching and real-time assessment for students. This paper discusses the application prospects for AI technology in the teaching practice of gastrointestinal oncology. Although AI technology shows great potential in the diagnosis and treatment of gastrointestinal tumors and teaching gastrointestinal oncology, it also has limitations and needs to be combined with traditional teaching methods to achieve the best teaching results.

Objective:To explore the clinical characteristics of patients with brucellosis complicated with epididymo-orchitis (Brucellar epididymo-orchitis, BEO), so as to provide reference for clinical diagnosis and treatment of BEO.Methods:General and clinical data of 293 male patients with acute brucellosis admitted to the Beidahuang Industry Group General Hospital from January 2023 to December 2024 were retrospectively collected. They were divided into a BEO group (30 cases) and a non-BEO group (263 cases) based on the presence or absence of epididymo-orchitis. Epidemic characteristics, clinical manifestations and laboratory examination results were compared and analyzed.Results:Among 293 male patients with acute brucellosis, the incidence of BEO was 10.24% (30/293). Their age was mainly concentrated in 45 - < 60 years old (53.33%, 16/30), and occupation was mostly farmers (63.33%, 19/30). There were no statistically significant differences in the distribution of age, occupation, exposure history and onset season between the BEO group and the non-BEO group ( P > 0.05). The distribution of abdominal pain and urinary frequency/urgency/pain symptoms was compared, and the differences were statistically significant ( P < 0.05). White blood cell count (WBC), neutrophil count (NEUT), and C-reactive protein (CRP) levels in the BEO group were higher than those in the non-BEO group ( P < 0.05), while the levels of cytokines interleukin (IL)-6 and interferon-γ (IFN-γ) were lower than those in the non-BEO group ( P < 0.05). After 6 - 8 weeks of hospitalization, the levels of WBC, NEUT, CRP, albumin, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, alkaline phosphatase, α-hydroxybutyrate dehydrogenase, lactate dehydrogenase, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-α, and IFN-γ in patients of the BEO group were significantly different from before treatment ( P < 0.05). Twenty-eight patients were cured, 1 patient underwent orchiectomy, and 1 patient experienced recurrence. Conclusions:Middle-aged male patients with brucellosis are more prone to BEO. Clinical manifestations and laboratory tests have certain diagnostic value for BEO. Suspected BEO patients should be diagnosed and treated as early as possible to reduce the occurrence of adverse prognosis.