ObjectiveTo investigate the therapeutic effect and mechanism of Huatan Qushi Huoxue prescription on rats with metabolic dysfunction-associated steatohepatitis （MASH）. MethodsA total of 60 specific pathogen-free Sprague-Dawley rats were randomly divided into blank control group， model A group， model B group， Western medicine group （polyene phosphatidylcholine， 143.64 mg/kg）， high-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 20.16 g/kg）， and middle-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 10.08 g/kg）. All rats except those in the blank control group were given high-fat diet. Samples were collected from the model A group at week 8， and since week 12， the other groups were given the corresponding drug once a day for 8 consecutive weeks， with samples collected at week 20. Body weight， liver wet weight， and liver index were measured for all rats； the microplate method was used to measure the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and free fatty acids （FFA）； ELISA was used to measure the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and soluble triggering receptor expressed on myeloid cells 2 （sTREM2）； HE staining and oil red O staining were performed to observe liver histopathological changes； immunofluorescence assay was used to measure CD68⁺TREM2⁺ cells in liver tissue and calculate the phagocytosis rate of macrophages； quantitative real-time PCR was used to measure the mRNA expression levels of sphingosine 1-phosphate （S1P）， sphingosine 1-phosphate receptor 1 （S1PR1）， a disintegrin and metalloproteinase 17 （ADAM17）， and triggering receptor expressed on myeloid cells 2 （TREM2） in liver tissue， and immunohistochemistry was used to measure the protein expression levels of S1P， S1PR1， ADAM17， and TREM2 in liver tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between groups， and the least significant difference t-test was used for further comparison between two groups； the Welch’s test was used for comparison of normally distributed continuous data with heterogeneity of variance between groups， and the Tamhane’s test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the blank control group， the model A group and the model B group had significant increases in body weight and liver wet weight， and the model B group had a significant increase in liver index （all P<0.05）. HE staining showed diffuse macrovesicular steatosis of liver tissue in the model A group and a large number of hepatocytes with ballooning degeneration in liver tissue in the model group B， with the presence of mixed inflammatory cell infiltration and mild perisinusoidal fibrosis in the lobules and the portal area. Compared with the blank control group， the model A group and the model B group had significant increases in NAS score and oil red O-positive area （all P<0.05）， and the model B group had significant increases in these two indicators than the model A group （both P<0.05）. Compared with the blank control group， the model A group and the model B group had significant increases in the serum levels of TC， TG， LDL-C， FFA， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C， and the model B group had significant increases in the serum levels of ALT， AST， and TNF-α （all P<0.05）； compared with the model A group， the model B group had significant increases in the serum levels of ALT， AST， TC， TG， FFA， TNF-α， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C （all P<0.05）. Immunofluorescence assay showed that compared with the blank control group， the model A group had a significant increase in the phagocytosis rate of macrophages （P<0.05）， while the model B group had a significantly lower phagocytosis rate of macrophages than the model A group （P<0.05）. Quantitative real-time PCR showed that compared with the blank control group， the model A group and the model B group had a significant increase in the mRNA expression level of TREM2， and the model B group had significant increases in the mRNA expression levels of S1P and S1PR1 （both P<0.05）； moreover， compared with the model A group， the model B group had significant increases in the mRNA expression levels of S1PR1 and TREM2 （both P<0.05）. Immunohistochemistry showed that compared with the blank control group， the model A group and the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17， and the model A group had a significant increase in the protein expression level of TREM2 （all P<0.05）； compared with the model A group， the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17 and a significant reduction in the protein expression level of TREM2 （all P<0.05）. Compared with the model B group， each medication group had significant reductions in body weight， liver wet weight， and liver index （all P<0.05）； each medication group had significant improvements in hepatic steatosis and inflammatory damage， with significant reductions in NAS score and oil red O-positive area （all P<0.05）； each medication group had significant reductions in the serum levels of ALT， AST， TC， TG， FFA， IL-1β， and IL-6 （all P<0.05） and a significant increase in the serum level of HDL-C （P<0.05）， and the high-dose Chinese medicine group had a significant reduction in the serum level of TNF-α （P<0.05）； each medication group had a significant increase in the phagocytosis rate of macrophages （all P<0.05）； the high- and middle-dose Chinese medicine groups had a significant reduction in the protein expression level of ADAM17， and the high-dose Chinese medicine group had a significant increase in the protein expression level of TREM2 （all P<0.05）. ConclusionHuatan Qushi Huoxue prescription improves lipid metabolism and inflammation in the liver of MASH rats by regulating hepatic macrophage phagocytosis.

OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway.

Background and Aims:Autoimmune thyroid disease(AITD)are closely associated with metabolic dysregulation,but the causal role of specific metabolites remains unclear.This study aimed to systematically evaluate the causal relationships between approximately 1 400 blood metabolites and two major AITD subtypes-Graves'disease(GD)and Hashimoto's thyroiditis(HT)-using a two-sample Mendelian randomization(MR)approach,to identify potential risk or protective metabolites and provide genetic evidence for mechanistic studies and targeted metabolic interventions.Methods:Summary-level genome-wide association study(GWAS)data for blood metabolites and AITDs were analyzed using inverse-variance weighted MR as the primary method,supplemented by MR-Egger,weighted median,and mode-based methods.Heterogeneity,pleiotropy,and robustness were assessed through Cochran's Q test,horizontal pleiotropy test,and leave-one-out analyses.Results:Forty-nine metabolites showed significant causal associations with GD and 89 with HT.Hexanoylglutamine and ceramide(d18∶1/16∶0)were identified as GD risk factors,while N2,N2-dimethylguanosine and β-hydroxyisovalerylcarnitine were protective.Pregnanediol sulfate and theobromine were associated with increased HT risk,whereas dihomo-linolenate(20:3n3 or n6)and caprylate appeared protective.The α-ketoglutarate/succinate ratio was positively associated with both diseases,suggesting a shared metabolic risk pathway.Conclusion:This MR study provides genetic evidence supporting causal links between multiple blood metabolites and GD or HT.Several metabolites may serve as predictive or protective biomarkers,offering novel insights into the pathophysiology,early screening,and personalized metabolic intervention strategies for AITDs.

Objective To evaluate the effects of Yiqi Huayu Jiedu Decoction combined with chemotherapy on disease-free survival rate and disease-free survival(DFS)of patients with stage Ⅱ and Ⅲ postoperative gastric cancer.Methods Totally 102 patients with stage Ⅱ and Ⅲ postoperative gastric cancer treated by Affiliated Hospital of Nanjing University of Chinese Medicine and Nanjing Drum Tower Hospital were selected.The patients were divided into control group(52 cases)and test group(50 cases)with block random method.The control group received conventional postoperative adjuvant chemotherapy for 4-6 cycles.The test group was treated with Chinese materia medica for 6 months on the basis of chemotherapy.Continue follow-up until the patients had recurrence,metastasis or death.DFS was analyzed by Kaplan-Meier method,and the average DFS of the two groups was estimated.Log Rank test was used to test the significance of differences in survival distribution between groups.Univariate and multivariate analyses of variables affecting prognosis were conducted using the Cox regression model.Adverse reactions of both groups were monitored.Results The recurrence and metastasis rate of the test group was 12.0%(6/50),while that of the control group was 34.6%(18/52),which was lower in the test group than in the control group(P<0.05).The 1-year and 2-year DFS rates and DFS of the control group were 86.5%,72.2%and 25.8 months respectively,while those of the test group were 95.6%,84.1%and 33.9 months respectively,with statistical significance(P=0.012).Cox-regression analysis suggested:The independent factors influencing the disease-free survival time of patients with gastric cancer were the test group(P=0.022),surgical methods of subtotal gastrectomy(P=0.038)and clinical stages Ⅱ(P=0.040).No adverse reactions related to Chinese materia medica were reported in the two groups.Conclusion Yiqi Huayu Jiedu Decoction combined with chemotherapy can improve the 1-year and 2-year DFS rate,prolong DFS,reduce the recurrence and metastasis rate,and improve the prognosis.

Objective To evaluate the effects of Yiqi Huayu Jiedu Decoction combined with chemotherapy on disease-free survival rate and disease-free survival(DFS)of patients with stage Ⅱ and Ⅲ postoperative gastric cancer.Methods Totally 102 patients with stage Ⅱ and Ⅲ postoperative gastric cancer treated by Affiliated Hospital of Nanjing University of Chinese Medicine and Nanjing Drum Tower Hospital were selected.The patients were divided into control group(52 cases)and test group(50 cases)with block random method.The control group received conventional postoperative adjuvant chemotherapy for 4-6 cycles.The test group was treated with Chinese materia medica for 6 months on the basis of chemotherapy.Continue follow-up until the patients had recurrence,metastasis or death.DFS was analyzed by Kaplan-Meier method,and the average DFS of the two groups was estimated.Log Rank test was used to test the significance of differences in survival distribution between groups.Univariate and multivariate analyses of variables affecting prognosis were conducted using the Cox regression model.Adverse reactions of both groups were monitored.Results The recurrence and metastasis rate of the test group was 12.0%(6/50),while that of the control group was 34.6%(18/52),which was lower in the test group than in the control group(P<0.05).The 1-year and 2-year DFS rates and DFS of the control group were 86.5%,72.2%and 25.8 months respectively,while those of the test group were 95.6%,84.1%and 33.9 months respectively,with statistical significance(P=0.012).Cox-regression analysis suggested:The independent factors influencing the disease-free survival time of patients with gastric cancer were the test group(P=0.022),surgical methods of subtotal gastrectomy(P=0.038)and clinical stages Ⅱ(P=0.040).No adverse reactions related to Chinese materia medica were reported in the two groups.Conclusion Yiqi Huayu Jiedu Decoction combined with chemotherapy can improve the 1-year and 2-year DFS rate,prolong DFS,reduce the recurrence and metastasis rate,and improve the prognosis.

To tackle the challenges posed by low resolution,weak contrast,and positional variations in liver tumor ultrasound images,which affects the diagnostic efficiency and accuracy,a novel method based on prototype generation and contrastive learning is proposed for liver tumor segmentation in ultrasound images.The core of this method is a weighted mask attention Transformer structure which utilizes the probabilities of real categories in the predicted probability distribution to weight image feature vectors,generates class prototypes with category discrimination,and thereby effectively captures key features while enhancing spatial information representation.By combining contrastive loss with Dice cross-entropy loss,the model achieves significant improvements in both category discrimination capability and segmentation accuracy,and overcomes the limitations of traditional models related to insufficient spatial information and intra-class pixel distribution imbalance.Comprehensive evaluations of the proposed method are conducted on a collected dataset of 253 ultrasound images,and the experimental results reveal that the proposed method attains a mean intersection-over-union of 78.44%and a Dice similarity coefficient of 87.41%,validating its superiority in liver tumor segmentation from ultrasound image.

Background and Aims:Autoimmune thyroid disease(AITD)are closely associated with metabolic dysregulation,but the causal role of specific metabolites remains unclear.This study aimed to systematically evaluate the causal relationships between approximately 1 400 blood metabolites and two major AITD subtypes-Graves'disease(GD)and Hashimoto's thyroiditis(HT)-using a two-sample Mendelian randomization(MR)approach,to identify potential risk or protective metabolites and provide genetic evidence for mechanistic studies and targeted metabolic interventions.Methods:Summary-level genome-wide association study(GWAS)data for blood metabolites and AITDs were analyzed using inverse-variance weighted MR as the primary method,supplemented by MR-Egger,weighted median,and mode-based methods.Heterogeneity,pleiotropy,and robustness were assessed through Cochran's Q test,horizontal pleiotropy test,and leave-one-out analyses.Results:Forty-nine metabolites showed significant causal associations with GD and 89 with HT.Hexanoylglutamine and ceramide(d18∶1/16∶0)were identified as GD risk factors,while N2,N2-dimethylguanosine and β-hydroxyisovalerylcarnitine were protective.Pregnanediol sulfate and theobromine were associated with increased HT risk,whereas dihomo-linolenate(20:3n3 or n6)and caprylate appeared protective.The α-ketoglutarate/succinate ratio was positively associated with both diseases,suggesting a shared metabolic risk pathway.Conclusion:This MR study provides genetic evidence supporting causal links between multiple blood metabolites and GD or HT.Several metabolites may serve as predictive or protective biomarkers,offering novel insights into the pathophysiology,early screening,and personalized metabolic intervention strategies for AITDs.

The morphological characteristics of hepatocellular carcinoma(HCC)tumor margins are pivotal in influencing patient's prognosis and the selection of therapeutic strategies.This paper re-viewed the classification methods of HCC tumor margins,ranging from traditional macroscopic classifi-cations to refined classification systems based on multi-omics analysis,and analyzed the role of these classification methods in guiding the formulation of personalized treatment plans.Additionally,this paper emphasized the crucial role of three-dimensional imaging techniques in assessing tumor margin morphology and outlined future research directions,including validating the effectiveness of multi-omics classification systems and developing new imaging and molecular biomarkers to achieve more precise treatment plans and prolong patient survival.

Siwu Decoction is a classic formula for tonifying the blood and activating blood circulation and is characterized by its ability to tonify the blood without leaving stasis and promote blood circulation without harming the vital energy of the body.It is widely used in clinical practice for the treatment of various conditions related to blood deficiency and poor blood circulation,such as anemia,menstrual disorders,and dysmenorrhea.The liver is responsible for governing the free flow of Qi and storing blood,and abnormalities in liver function are associated with various acute and chronic liver injuries.Siwu Decoction can restore liver homeostasis by tonifying the blood,activating blood circulation,nourishing the blood,and soothing the liver.Based on its unique prescription formulation and multiple pharmacological mechanisms,Siwu Decoction has become an important prescription for enhancing liver microcirculation,facilitating hepatocyte repair and regeneration,and alleviating liver injury.This article reviews the effect and mechanism of Siwu Decoction in the prevention and treatment of various liver injuries(including alcoholic liver disease,nonalcoholic fatty liver disease,nonalcoholic fatty liver disease,liver fibrosis,and liver cirrhosis)and discusses existing problems and future research directions.