This paper proposes a two-stage method integrating visual foundation models （VFM） and diffusion models. The segment anything model （SAM） as VFM is combined with the SegRefiner diffusion model to construct the SAM-SegRefiner framework for automated segmentation of edema， inflammation， and thrombus regions in histopathological images of hemorrhoidal tissue， providing a reproducible technical tool for the objective quantification of pathological morphology and its application in traditional Chinese medicine （TCM） syndrome research. Trained and validated on multi-center retrospective data， the SAM-SegRefiner model achieved an average pixel accuracy of 95.32% and a mean intersection over union （mIoU） of 66.81% on an independent test set， significantly outperfor-ming comparative models such as U-Net， MixU-Net， and SAM-Med2D， and also demonstrating robust cross-center generalization capability. Furthermore， by correlating the quantitatively segmented results from the model with the patients' TCM syndrome types， the potential associations between pathomorphological features and TCM syndrome differentiation have been explored. The analysis revealed no statistically significant differences in the degree of inflammatory infiltration and thrombus formation among different syndrome types， suggesting a complex relationship between local pathological changes and systemic syndrome manifestations.

Objective To observe the effects of Hedysarum Polybotrys polysaccharide(HPS)on the glucose metabolism of small intestinal smooth muscle in rats with diabetic gastroparesis(DGP)of spleen qi deficiency syndrome;To explore its mechanism based on AMPK/GLUT4 signaling pathway.Methods Totally 72 male Wistar rats were randomly divided into 12 in the blank group and the remaining 60 rats were assigned to the model group.The DGP spleen qi deficiency syndrome model was replicated by intraperitoneal injection of streptozotocin+irregular feeding with high-fat and high sugar feed combined with swimming exhaustion method.The model rats were randomly divided into model group,metformin group and HPS high-,medium-and low-dosage groups.The metformin group was given 100 mg/kg metformin hydrochloride by gavage,while the HPS high-,medium-and low-dosage groups were given 200,100 and 50 mg/kg HPS by gavage,respectively.The blank group and model group were given purified water by gavage once a day for 8 consecutive weeks.The gastric emptying rate and small intestine propulsion rate in rats were detected,HE staining was used to observe the smooth muscle morphology of gastric antrum and ileal tissue,immunofluorescence staining was used to detect the expression of glucagon like peptide-1(GLP-1)in ileal tissue,ELISA was used to detect the contents of adiponectin(APN),glucagon(Glu)and insulin(INS)in serum,Western blot was used to detect the protein expressions of glucose transporter(GLUT)4,GLUT1,AMP-activated protein kinase(AMPK)and p-AMPK in ileal tissue.Results Compared with the blank group,the model group rats showed significantly increased random blood glucose,significantly decreased body mass,gastric emptying rate and small intestinal propulsion rate(P<0.01);the edema in the submucosal layer,loose arrangement of connective tissue,infiltration of a small number of lymphocytes,granulocytes and macrophages,reduced number of goblet cells in the ileal tissue,shedding of intestinal villous epithelial cells and widening of the gap between the submucosal layer and the lamina propria;the expression of GLP-1 in ileal tissue was significantly decreased(P<0.05),the contents of serum APN and INS were significantly decreased,and the content of Glu significantly increased(P<0.01),the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue were significantly decreased,while the expression of GLUT1 protein significantly increased(P<0.01).Compared with the model group,rats in metformin group and HPS high-dosage group showed a random decrease in blood glucose,an increase in body mass,gastric emptying rate,and small intestine propulsion rate(P<0.05,P<0.01);a more regular arrangement of gastric antral tissue cells,a reduction of shedding cells and edema,the smooth muscle structure of the ileal tissue was relatively intact,with evenly distributed cells and reduced infiltration of inflammatory cells;the expression of GLP-1 in ileal tissue increased,the contents of serum APN and INS increased,and the content of Glu decreased,the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue increased,while the expression of GLUT1 protein decreased(P<0.05,P<0.01).Conclusion HPS may up-regulate GLUT4 and down-regulate GLUT1 expression through activates AMPK,promotes glucose uptake and utilization by small intestinal smooth muscle,and improves glucose metabolism of DGP rats with spleen qi deficiency syndrome.

Objective To observe the effects of Angelica and Astragalus ultrafiltration membrane extracts on Keap1/Nrf2 signaling pathway-related factors in diabetes kidney disease(DKD)model rats;To explore its mechanism in treating oxidative stress injury of DKD.Methods Totally 70 SPF-grade male SD rats were randomly divided into 10 rats for the blank group and the remaining 60 rats were fed with high-sugar and high-fat diet,streptozotocin was intraperitoneally injected after 4 weeks to establish the DKD model.The established model rats were randomly divided into the model group,positive control group(GKT137831 30 mg/kg)and TCM high-,medium-and low-dosage groups(Angelica and Astragalus ultrafiltration membrane extracts 6,3,1.5 g/kg),which were orally administered with corresponding drugs.The blank group and model group were given equivalent volume of distilled water orally once daily for 12 consecutive weeks.Random blood glucose,body mass and 24 h urinary total protein content(24 h-UTP)were detected,biochemical assays were conducted to detect serum creatinine(SCr),blood urea nitrogen(BUN),triglycerides(TG),total cholesterol(TC)and albumin(ALB)contents,HE and Masson staining were used to observe the morphology in renal tissue,the contents of reactive oxygen species(ROS),glutathione(GSH)and malondialdehyde(MDA)were measured by ELISA,the protein expressions of nicotinamide adenine dinucleotide phosphate oxidase 4(Nox4),Kelch-like ECH-associated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2),glutamate-cysteine ligase modifier subunit(GCLM)and glutathione peroxidase 4(GPX4)in renal tissue were detected by Western blot.Results Compared with the blank group,the random blood glucose at each time point of model group rats significantly increased(P<0.01),the 24 h-UTP significantly increased(P<0.01),the contents of SCr,BUN and serum TG,TC increased(P<0.01),and ALB content decreased(P<0.01);with loose arrangement and disordered structure of renal tissue,consolidation of glomeruli,shedding of renal tubular epithelial cells,and increased deposition of collagen fibers;the contents of serum ROS and MDA were significantly elevated(P<0.01),while GSH contents decreased(P<0.01);the protein expression of Nox4 and Keap1 in renal tissue significantly increased(P<0.01),the expression of Nrf2,GCLM and GPX4 protein significantly decreased(P<0.01).Compared with the model group,the random blood glucose were significantly reduced at 6,8,10,12 weeks in the treatment groups(P<0.01),24 h-UTP decreased(P<0.01),the contents of SCr,BUN,TG,TC in positive control group and TCM high-,medium-dosage group decreased,with increased ALB content(P<0.01,P<0.05);renal tubular and glomerular lesions were improved,and collagen fiber proliferation decreased;serum ROS and MDA contents were reduced,while GSH content increased(P<0.01,P<0.05);the protein expression of Nox4 and Keap1 in renal tissue decreased(P<0.01),and Nrf2,GCLM and GPX4 protein expression increased(P<0.01).Conclusion Angelica and Astragalus ultrafiltration membrane extracts can effectively alleviate injury of renal tissue in DKD rats,and its mechanism may be related to the regulation of the Keap1/Nrf2 signaling pathway and inhibition of oxidative stress response.

Objective To investigate the effects of cornuside on intestinal injury in rats with septic shock,and clarify its possible mechanism.Methods SD rats were randomly divided into normal control group,model group,low-,medium-,and high-dose comecarpine glycosides groups,and TREM1 inhibitor(LR12)group.HE staining was used to observe the pathological injury of small intestinal mucosa.The levels of D-lactic acid(D-LA)and diamine oxidase(DAO)in serum and secretory immunoglobulin(sIg A)in small intestine were detected by ELISA.Intestinal mucosal permeability was detected by fluorescein isothiocyanate-dextran(FITC-D)tracer method.ELISA was used to detect the levels of interferon(IFN)-γ,tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-10 and arginase(Arg)-1 in serum.The polarization of macrophages in small intestinal tissue was detected by flow cytometry.Western blot was used to detect the protein expression levels of triggering receptor expressed on myeloid cells 1(TREM1),CD86 and CD206 in small intestine.Results Compared with the normal control group,the model group had serious pathological injury of the small intestinal mucosa,and the serum levels of D-LA,DAO,FITC-D,IFN-γ,TNF-α,and IL-1β significantly increased(P<0.05),while the levels of sIg A,IL-10,and Arg-1 significantly decreased(P<0.05).The M1/M2 ratio of macrophages and the expression levels of TREM1 and CD86 proteins in the small intestine tissue significantly increased(P<0.05),while the expression level of CD206 protein significantly decreased(P<0.05).Compared with the model group,the small intestinal mucosal injury of the rats in each dose cornuside group and LR12 group significantly improved,and the serum levels of D-LA,DAO,FITC-D,IFN-γ,TNF-α,and IL-1β significantly decreased(P<0.05),while the levels of sIg A,IL-10,and Arg-1 significantly increased(P<0.05).The M1/M2 ratio of macrophages and the expression levels of TREM1 and CD86 proteins in the small intestine tissue significantly decreased(P<0.05),while the expression level of CD206 protein significantly increased(P<0.05).Conclusion Cornuside can reduce intestinal injury in rats with septic shock,and the mechanism may be related to inhibiting TREM1-mediated M1 polarization of macrophages.

Objective:To investigate the possible mechanism of Zaogong Erteng decoction (ZGETD) in the treatment of endometritis.Methods:Femal mice were injected 2.5 mg/mL lipopolysaccharide into uterine horn to induce endometritis model. After modelling, low-dose ZGETD, high-dose ZGETD or amoxicillin was given once a day for 7 d. The appearance of the uterus and pathological changes of uterine tissue were observed 7 d later, and the uterine index was calculated. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in mouse uterine tissue was detected by enzyme-linked immunosorbent assay. The activity of myeloperoxidase (MPO) in mouse uterine tissue was measured by redox reaction. The active ingredients of ZGETD and the target and signal pathway of treatment of endometritis were analyzed by network pharmacology. Western blotting and qRT-PCR were used to detect the expressions of Toll-like receptor 4 (TLR4), P65, p-P65, interferon regulatory factor 3 (IRF3) and p-IRF3 proteins and chemokines CXCL5 and CXCL8 in the mouse uterus, respectively. Terminal dUTP nick end labeling detected endometrial cell apoptosis and endometrial thickness was measured. After treatment, the female rats were mated with the male rats, and the mating rate, the pregnancy rate and the number of implantation sits in the injected uterine horn on day 8 of gestation were counted. Results:Both ZGETD and amoxicillin have atherapeutic effect on endometritis, but compared with low-dose ZGETD and amoxicillin, high-dose ZGETD can significantly alleviate the edema and congestion of uterine tissue and reduce the uterine index (all P=0.001). After treatment, the uterine cavity epithelium of mice was smooth and complete, the uterine gland structure was normal, and no bleeding area and inflammatory cell aggregation were observed. Compared with amoxicillin, high-dose ZGETD significantly decreased the expression of inflammatory factors (TNF-α, IL-1β and IL-6) and MPO activity (all P<0.001). The expression of chemokines ( CXCL5 and CXCL8) was significantly reduced (all P<0.05). The signaling pathways TLR4, nuclear factor kappa-B (NF-κB) and TNF related to the treatment of endometritis by ZGETD were screened by network pharmacology, and their action targets (TLR4, NF-κB and IRF3) were verified. Quercetin, fisetin and luteolin were found to be the most active ingredients acting on these targets. High-dose ZGETD significantly inhibited the activation of TLR4/NF-κB and TLR4/IRF3 pathways ( P<0.05), decreased endometrial cell apoptosis ( P<0.05), and increased endometrial thickness ( P<0.001), mating rate ( P<0.001), pregnancy rate ( P<0.001) and implantation site number of uterine horn on the injection side of LPS after treatment ( P=0.001). Conclusion:High-dose ZGETD has a significant therapeutic effect on endometritis, which may be closely related to the down-regulation of TLR4 signaling pathway.

Objective To explore the effectiveness of the diffusion of innovation theory in com-bination with multidisciplinary nursing collaboration in intervention for patients with severe pneumonia complicated by heart failure.Methods A total of 120 patients with severe pneumonia complicated by heart failure admitted between April 2021 and April 2024 were enrolled and randomly divided into observation group(n=60)and control group(n=60)using a random black-and-white ball method.The control group received conventional nursing intervention,while the observation group received an intervention model combining the diffusion of innovations theory with multidisciplinary collaboration on top of the conventional nursing.Rehabilitation outcomes(time to control of pulmonary inflammation,time to resolution of cough and expectoration,length of hospital stay)and post-intervention cardiac function[left ventricular ejection fraction(LVEF),left ventricular end-systolic volume(LVESV)]were compared between the two groups.The Minnesota Living with Heart Failure Questionnaire(MLHFQ)was used to assess quality of life,and the Self-Care Heart Failure Index(SCHFI)was used to evaluate self-care behaviors.Complications were compared between the two groups,and cost-effectiveness was analyzed(patient medical expenses and re-hospitalization rates).Results The observation group had shorter time to resolution of cough and expectoration,control of pulmonary inflammation,and length of hospital stay compared with the control group,with statistically significant differences(P＜0.05).After intervention,LVEF increased in both groups compared with pre-intervention lev-els,and was higher in the observation group than in the control group,with a statistically significant difference(P＜0.05);ESV decreased in both groups compared with pre-intervention levels,and was lower in the observation group than in the control group,with a statistically significant difference(P＜0.05).After intervention,physiological,emotional,and social functioning scores in the MLHFQ decreased in both groups compared with pre-intervention levels,and were lower in the ob-servation group than in the control group,with statistically significant differences(P＜0.05).After intervention,scores for self-care maintenance,self-care management,and self-care confidence in the SCHFI increased in both groups,and were higher in the observation group than in the control group,with statistically significant differences(P＜0.05).There was no statistically significant difference in the incidence of complications between the two groups(P＞0.05).Conclusion The combination of the diffusion of innovations theory and multidisciplinary collaboration nursing model can accelerate the rehabilitation process in patients with severe pneumonia complicated by heart fail-ure,improve their quality of life,and effectively enhance their self-care abilities.

Objective:To investigate the possible mechanism of Zaogong Erteng decoction (ZGETD) in the treatment of endometritis.Methods:Femal mice were injected 2.5 mg/mL lipopolysaccharide into uterine horn to induce endometritis model. After modelling, low-dose ZGETD, high-dose ZGETD or amoxicillin was given once a day for 7 d. The appearance of the uterus and pathological changes of uterine tissue were observed 7 d later, and the uterine index was calculated. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in mouse uterine tissue was detected by enzyme-linked immunosorbent assay. The activity of myeloperoxidase (MPO) in mouse uterine tissue was measured by redox reaction. The active ingredients of ZGETD and the target and signal pathway of treatment of endometritis were analyzed by network pharmacology. Western blotting and qRT-PCR were used to detect the expressions of Toll-like receptor 4 (TLR4), P65, p-P65, interferon regulatory factor 3 (IRF3) and p-IRF3 proteins and chemokines CXCL5 and CXCL8 in the mouse uterus, respectively. Terminal dUTP nick end labeling detected endometrial cell apoptosis and endometrial thickness was measured. After treatment, the female rats were mated with the male rats, and the mating rate, the pregnancy rate and the number of implantation sits in the injected uterine horn on day 8 of gestation were counted. Results:Both ZGETD and amoxicillin have atherapeutic effect on endometritis, but compared with low-dose ZGETD and amoxicillin, high-dose ZGETD can significantly alleviate the edema and congestion of uterine tissue and reduce the uterine index (all P=0.001). After treatment, the uterine cavity epithelium of mice was smooth and complete, the uterine gland structure was normal, and no bleeding area and inflammatory cell aggregation were observed. Compared with amoxicillin, high-dose ZGETD significantly decreased the expression of inflammatory factors (TNF-α, IL-1β and IL-6) and MPO activity (all P<0.001). The expression of chemokines ( CXCL5 and CXCL8) was significantly reduced (all P<0.05). The signaling pathways TLR4, nuclear factor kappa-B (NF-κB) and TNF related to the treatment of endometritis by ZGETD were screened by network pharmacology, and their action targets (TLR4, NF-κB and IRF3) were verified. Quercetin, fisetin and luteolin were found to be the most active ingredients acting on these targets. High-dose ZGETD significantly inhibited the activation of TLR4/NF-κB and TLR4/IRF3 pathways ( P<0.05), decreased endometrial cell apoptosis ( P<0.05), and increased endometrial thickness ( P<0.001), mating rate ( P<0.001), pregnancy rate ( P<0.001) and implantation site number of uterine horn on the injection side of LPS after treatment ( P=0.001). Conclusion:High-dose ZGETD has a significant therapeutic effect on endometritis, which may be closely related to the down-regulation of TLR4 signaling pathway.

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

Objective To establish the fingerprints and predict the quality markers of Sanqi Shenfeng oral liquid based on fingerprint and network pharmacology.Methods The fingerprints of 12 batches of Sanqi Shenfeng oral liquid were established by using HPLC,and their peaks were identified and assigned.The candidate components were selected by multiple statistical analysis methods such as similarity evaluation,hierarchical cluster analysis,principal component analysis and orthogonal partial least squares discrimination analysis(OPLS-DA).The"component-target-pathway"network diagram was constructed by network pharmacology,and the quality markers of Sanqi Shenfeng oral liquid were predicted.Results The 13 common peaks were identified from the established fingerprint.Compared with the reference material,eight common peaks were identified as 3(tetrahydroxystilbene glucoside),5(sodium benzoate),6(lobetyolin),7(notoginsenoside Ri),9(ginsenoside Rgi),10(ginsenoside Re),12(10-hydroxy-2-decenoic acid),13(ginsenoside Rb1).The similarity of 12 batches of Sanqi Shenfeng oral liquid samples was higher than 0.997,and 12 batches of samples were grouped into two categories.OPLS-DA analysis showed that peaks 2,3,4,7,9,10,11,12 were the main signature components affecting the quality of Sanqi Shenfeng oral liquid.Network pharmacology predicted that lobetyolin,notoginsenoside R1,ginsenoside Rg1,ginsenoside Rb1,ginsenoside Re and 10-hydroxy-2-decenoic acid were potential Q-markers of Sanqi Shenfeng oral liquid.The traditional functions are performed through STAT3/AKT1-Drp1,HIF-1 and PI3K-AKT signaling pathway.Conclusion The established fingerprint has good reproducibility,stability and feasibility.The six components have great influence on the quality of Sanqi Shenfeng oral liquid,which are transferable and traceable,and are closely related to the efficacy.They can be used as potential quality markers to provide a scientific basis for the quality control and evaluation of Sanqi Shenfeng oral liquid.

Objective To investigate the effects of cornuside on intestinal injury in rats with septic shock,and clarify its possible mechanism.Methods SD rats were randomly divided into normal control group,model group,low-,medium-,and high-dose comecarpine glycosides groups,and TREM1 inhibitor(LR12)group.HE staining was used to observe the pathological injury of small intestinal mucosa.The levels of D-lactic acid(D-LA)and diamine oxidase(DAO)in serum and secretory immunoglobulin(sIg A)in small intestine were detected by ELISA.Intestinal mucosal permeability was detected by fluorescein isothiocyanate-dextran(FITC-D)tracer method.ELISA was used to detect the levels of interferon(IFN)-γ,tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-10 and arginase(Arg)-1 in serum.The polarization of macrophages in small intestinal tissue was detected by flow cytometry.Western blot was used to detect the protein expression levels of triggering receptor expressed on myeloid cells 1(TREM1),CD86 and CD206 in small intestine.Results Compared with the normal control group,the model group had serious pathological injury of the small intestinal mucosa,and the serum levels of D-LA,DAO,FITC-D,IFN-γ,TNF-α,and IL-1β significantly increased(P<0.05),while the levels of sIg A,IL-10,and Arg-1 significantly decreased(P<0.05).The M1/M2 ratio of macrophages and the expression levels of TREM1 and CD86 proteins in the small intestine tissue significantly increased(P<0.05),while the expression level of CD206 protein significantly decreased(P<0.05).Compared with the model group,the small intestinal mucosal injury of the rats in each dose cornuside group and LR12 group significantly improved,and the serum levels of D-LA,DAO,FITC-D,IFN-γ,TNF-α,and IL-1β significantly decreased(P<0.05),while the levels of sIg A,IL-10,and Arg-1 significantly increased(P<0.05).The M1/M2 ratio of macrophages and the expression levels of TREM1 and CD86 proteins in the small intestine tissue significantly decreased(P<0.05),while the expression level of CD206 protein significantly increased(P<0.05).Conclusion Cornuside can reduce intestinal injury in rats with septic shock,and the mechanism may be related to inhibiting TREM1-mediated M1 polarization of macrophages.