ObjectiveTo investigate the effects of Yueju Wan on the 5-hydroxytryptamine （5-HT） signaling pathway in rats with functional dyspepsia （FD） and to explore its therapeutic mechanism in the treatment of FD. MethodsSixty Sprague-Dawley （SD） rats were randomly divided into a normal group， model group， mosapride group （1.575 mg·kg^-1）， and Yueju Wan low-， medium-， and high-dose groups （0.735， 1.47， and 2.94 g·kg^-1， respectively）. The FD rat model was established using GUO's tail-clamping stimulation combined with irregular feeding. After 14 days of modeling， rats were administered the corresponding drugs by gavage for 28 days. After treatment， gastric emptying rate and small intestinal propulsion rate were measured. Serum levels of 5-HT， tryptophan hydroxylase （TPH）， and substance P （SP） were detected by enzyme-linked immunosorbent assay （ELISA）， and acetylcholine （ACh） levels were determined by chemical methods. Histopathological changes in the gastric antrum were observed using hematoxylin-eosin （HE） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to assess the mRNA and protein expression levels of 5-hydroxytryptamine 4 receptor （5-HT4R）， SP， and acetylcholinesterase （AChE） in colon tissue， as well as 5-hydroxytryptamine 3 receptor （5-HT3R）， SP， and AChE in hypothalamic tissue. Immunohistochemistry （IHC） was used to examine the expression of 5-HT and 5-HT4R in the colon and 5-HT and 5-HT3R in the hypothalamus. ResultsCompared with the normal group， the gastric emptying rate and small intestinal propulsion rate in the model group were significantly decreased （P<0.01）. Serum levels of 5-HT， SP， ACh， and TPH were significantly reduced （P<0.01）. Histopathological examination revealed irregular arrangement of glands in the gastric antrum， slight mucosal atrophy， and mild inflammatory cell infiltration. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue， as well as 5-HT3R， SP， and AChE in hypothalamic tissue， were significantly decreased （P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was also significantly reduced （P<0.01）. Compared with the model group， all Yueju Wan groups showed significantly increased gastric emptying rate and small intestinal propulsion rate （P<0.01）. The glands in the gastric antrum were more regularly arranged， with no inflammatory cell infiltration observed. Serum levels of 5-HT， SP， ACh， and TPH were significantly increased （P<0.01）. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue and 5-HT3R， SP， and AChE in hypothalamic tissue were significantly upregulated （P<0.05， P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was significantly increased （P<0.01）. ConclusionYueju Wan has preventive and therapeutic effects on FD， and its mechanism may be related to regulation of the 5-HT signaling pathway， promotion of brain-gut peptide secretion， and enhancement of gastric motility.

OBJECTIVES: Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer. METHODS: The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes. RESULTS: Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm. CONCLUSIONS Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female ; Ovarian Neoplasms/metabolism* ; Animals ; Carcinoma, Ovarian Epithelial ; Disease Models, Animal ; Humans ; Neoplasms, Glandular and Epithelial/metabolism* ; Ovary/pathology*

OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

Regarding the challenge of early identification of critically ill patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD),a radiomics-clinical fusion model is proposed based on non-contrast CT images of accessory respiratory muscles to predict life-threatening conditions.A retrospective study is conducted involving 233 AECOPD patients(153 non-life-threatening and 80 life-threatening cases).Patients are divided into a training set(n=186)and a test set(n=47)at a 4:1 ratio.A total of 1 874 radiomic features are extracted from the erector spinae and pectoralis muscle regions delineated by radiologists on non-contrast CT images,and the features selection is performed using maximum relevance minimum redundancy and least absolute shrinkage and selection operator(LASSO)algorithms.Meanwhile,clinical data are analyzed with t-test and LASSO for variable screening.The selected features are input into C-support vector classification,Logistic regression,random forest,adaptive boosting(AdaBoost),and extreme gradient boosting(XGBoost)to construct radiomics model,clinical model,and fusion model.Predictive performance and clinical practicality are evaluated in the test set using receiver operating characteristic curve,area under the curve(AUC),and decision curve analysis.The radiomics-clinical fusion model built with XGBoost outperformed standalone radiomics and clinical models,achieving an AUC of 0.902(95％CI 0.846,0.994),with accuracy,sensitivity,specificity,and precision of 0.837,0.933,0.786,and 0.7,respectively.Results demonstrate that the fusion model based on the non-contrast CT radiomics of accessory respiratory muscles and clinical data exhibits promising diagnostic performance,highlighting its potential clinical significance for stratified management and preemptive critical care intervention in AECOPD patients.

Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10 /L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.

ObjectiveTo investigate the protective effect of Xielitang on dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group， a model group， a sulfasalazine group （0.6 g·kg^-1）， and low-， medium-， and high-dose Xielitang groups （1.67， 3.34， 6.68 g·kg^-1）. After treatment for 42 d， the colon length was recorded， and the disease activity index （DAI） score was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10）. Hematoxylin-eosin （HE） staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor （FXR）， small heterodimer partner （SHP）， liver receptor homolog-1 （LRH-1）， cholesterol 7α-hydroxylase （CYP7A1）， and fibroblast growth factor receptor 4 （FGFR4） in liver and FXR， sodium-dependent bile acid transporter （ASBT）， and fibroblast growth factor 15 （FGF15） in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover， ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group， the model group showed significantly decreased colon length， IL-10 content， α-diversity index， abundance of Firmicutes and Lactobacillus， and content of deoxycholic acid （DCA） and lithocholic acid （LCA） （P<0.01）， significantly increased DAI score， IL-6 and TNF-α content， abundance of Bacteroidetes， and the content of cholic acid （CA）， chenodeoxycholic acid （CDCA）， and taurocholic acid （TCA） （P<0.05， P<0.01）， significantly down-regulated protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. In addition， the structure of colonic mucosa was destroyed， and inflammatory cells infiltrated in the model group. Compared with the model group， Xielitang could significantly increase the colon length， IL-10 content， α-diversity index， the abundance of Firmicutes and Lactobacillus， and DCA and LCA content （P<0.05， P<0.01）， decrease DAI score， abundance of Bacteroidetes， and the content of IL-6， TNF-α， CA， CDCA， and TCA （P<0.01）， up-regulate the protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and down-regulate the protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis， regulating intestinal flora imbalance， and maintaining bile acid homeostasis.

As China has become the second largest market for medical devices in the world,the domestic medical device industry has been growing.As an important part of preclinical evaluation of medical devices,large animal research directly affects the research and application of medical devices.Large animals are widely used in the evaluation of safety and feasibility of medical devices because they are closer to humans in terms of body size,anatomical structure and physiological functions.In large animal experimental research,the selection of suitable experimental animals and the establishment of suitable animal disease models are the basis for ensuring the smooth progress of experiments.In this paper,the selection of experimental animals and the establishment of disease models in medical device large animal experimental research are systematically sorted out,and the existing problems and deficiencies are pointed out.

Objective To investigate the perioperative use of antimicrobial agents in class Ⅰ incisional ophthalmic surgeries in secondary first-class and above medical institutions in Shanghai City,and provide a basis for the rational use of antimicrobial agents in such surgeries.Methods Perioperative antimicrobial prophylaxis(PAP)in patients undergoing class Ⅰ incisional ophthalmic surgery reported by secondary first-class and above hospitals in Shanghai City from 2017 to 2022 was collected retrospectively.The prophylactic use rate,types,rationality of selection,and timing of use of antimicrobial agents were analyzed comprehensively.Results From 2017 to 2022,a total of 54 868 cases of class Ⅰ incisional ophthalmic surgeries were reported from secondary first-class and above hospitals in Shanghai City.The PAP rates in tertiary comprehensive hospitals,tertiary specialty hospitals,tertiary traditional Chinese medicine hospitals,and secondary comprehensive hospitals were 4.72％,1.79％,3.22％,and 6.63％,re-spectively.The overall PAP rate showed a yearly decreasing trend,from 6.39％in 2017 to 2.31％in 2021.Among different types of hospitals,the PAP rate in secondary comprehensive hospitals decreased most significantly,from 12.72％in 2017 to 0.53％in 2022.The main types of prophylactic antimicrobial use were first-,second-and third-generation cephalosporins,and quinolones.The rational selection rates of antimicrobial agents were highest in ter-tiary comprehensive hospitals(17.13％)and lowest in tertiary specialty hospitals(1.08％).The PAP rates in sys-temic veins 0.5-1 hour before surgery were highest in tertiary specialty hospitals(88.17％)and lowest in tertiary comprehensive hospitals(71.53％).The withdrawal rates of antimicrobial agents within 24 hours after surgery were highest in tertiary traditional Chinese medicine hospitals(80.87％)and lowest in tertiary specialty hospitals(13.26％).Conclusion The PAP for class Ⅰ incisional ophthalmic surgeries in secondary first-class and above medical institutions in Shanghai City still presents certain irrational phenomena in terms of antimicrobial types and administration routes.The administration rate 0.5-1 hour before surgery and withdrawal rate of antimicrobial agents within 24 hours after surgery need to be further improved.Enhanced management is necessary to promote more rational use of antimicrobial agents.

Regarding the challenge of early identification of critically ill patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD),a radiomics-clinical fusion model is proposed based on non-contrast CT images of accessory respiratory muscles to predict life-threatening conditions.A retrospective study is conducted involving 233 AECOPD patients(153 non-life-threatening and 80 life-threatening cases).Patients are divided into a training set(n=186)and a test set(n=47)at a 4:1 ratio.A total of 1 874 radiomic features are extracted from the erector spinae and pectoralis muscle regions delineated by radiologists on non-contrast CT images,and the features selection is performed using maximum relevance minimum redundancy and least absolute shrinkage and selection operator(LASSO)algorithms.Meanwhile,clinical data are analyzed with t-test and LASSO for variable screening.The selected features are input into C-support vector classification,Logistic regression,random forest,adaptive boosting(AdaBoost),and extreme gradient boosting(XGBoost)to construct radiomics model,clinical model,and fusion model.Predictive performance and clinical practicality are evaluated in the test set using receiver operating characteristic curve,area under the curve(AUC),and decision curve analysis.The radiomics-clinical fusion model built with XGBoost outperformed standalone radiomics and clinical models,achieving an AUC of 0.902(95％CI 0.846,0.994),with accuracy,sensitivity,specificity,and precision of 0.837,0.933,0.786,and 0.7,respectively.Results demonstrate that the fusion model based on the non-contrast CT radiomics of accessory respiratory muscles and clinical data exhibits promising diagnostic performance,highlighting its potential clinical significance for stratified management and preemptive critical care intervention in AECOPD patients.

Objective To investigate the perioperative use of antimicrobial agents in class Ⅰ incisional ophthalmic surgeries in secondary first-class and above medical institutions in Shanghai City,and provide a basis for the rational use of antimicrobial agents in such surgeries.Methods Perioperative antimicrobial prophylaxis(PAP)in patients undergoing class Ⅰ incisional ophthalmic surgery reported by secondary first-class and above hospitals in Shanghai City from 2017 to 2022 was collected retrospectively.The prophylactic use rate,types,rationality of selection,and timing of use of antimicrobial agents were analyzed comprehensively.Results From 2017 to 2022,a total of 54 868 cases of class Ⅰ incisional ophthalmic surgeries were reported from secondary first-class and above hospitals in Shanghai City.The PAP rates in tertiary comprehensive hospitals,tertiary specialty hospitals,tertiary traditional Chinese medicine hospitals,and secondary comprehensive hospitals were 4.72％,1.79％,3.22％,and 6.63％,re-spectively.The overall PAP rate showed a yearly decreasing trend,from 6.39％in 2017 to 2.31％in 2021.Among different types of hospitals,the PAP rate in secondary comprehensive hospitals decreased most significantly,from 12.72％in 2017 to 0.53％in 2022.The main types of prophylactic antimicrobial use were first-,second-and third-generation cephalosporins,and quinolones.The rational selection rates of antimicrobial agents were highest in ter-tiary comprehensive hospitals(17.13％)and lowest in tertiary specialty hospitals(1.08％).The PAP rates in sys-temic veins 0.5-1 hour before surgery were highest in tertiary specialty hospitals(88.17％)and lowest in tertiary comprehensive hospitals(71.53％).The withdrawal rates of antimicrobial agents within 24 hours after surgery were highest in tertiary traditional Chinese medicine hospitals(80.87％)and lowest in tertiary specialty hospitals(13.26％).Conclusion The PAP for class Ⅰ incisional ophthalmic surgeries in secondary first-class and above medical institutions in Shanghai City still presents certain irrational phenomena in terms of antimicrobial types and administration routes.The administration rate 0.5-1 hour before surgery and withdrawal rate of antimicrobial agents within 24 hours after surgery need to be further improved.Enhanced management is necessary to promote more rational use of antimicrobial agents.