ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Objective To investigate the predictive value of fluid-attenuated inversion recovery(FLAIR)vascular hyperintensity(FVH)combined with clinical indicators for the prognosis of intravenous thrombolysis in patients with acute cerebral infarction caused by middle cerebral artery(MCA)stenosis or occlusion.Methods This study retrospectively and consecutively enrolled patients with acute cerebral infarction caused by MCA stenosis or occlusion who underwent intravenous thrombolysis within 4.5 h of symptom onset at the Department of Neurology,Tianjin Huanhu Hospital,between January 2022 and October 2024.Baseline clinical data were collected,including sex,age,stroke risk factors(hypertension,diabetes,coronary heart disease,atrial fibrillation,prior stroke history,smoking,alcohol use),pre-thrombolysis blood pressure,National Institutes of Health stroke scale(NIHSS)score,serological markers(white blood cells,neutrophils,lymphocytes,blood glucose,uric acid,creatinine),completeness of the Willis circle,and thrombolysis time window(onset-to-treatment time:＜3.0h vs.3.0-4.5 h).FVH was assessed before thrombolysis using the Lee scoring system(0,1,or 2 points)based on FLAIR imaging.Inter-rater reliability for FVH scores between two radiologists was evaluated using Cohen's Kappa coefficient,with agreement levels defined as follows:almost perfect(Kappa value 0.81-1.00),substantial(Kappa value 0.61-0.80),moderate(Kappa value 0.41-0.60),fair(Kappa value 0.21-0.40),or slight/none(Kappa≤0.20).At 90 d post-thrombolysis,telephone follow-up was conducted to assess functional outcomes using the modified Rankin scale(mRS).Patients were dichotomized into favorable outcome group(mRS score 0-2)and poor outcome group(mRS score 3-6).Variables with statistical significance in univariate analysis underwent collinearity testing via variance inflation factor(VIF).Predictors with high collinearity(VIF＞10)were excluded,and the remaining variables were incorporated into a multivariate Logistic regression model to identify independent risk factors for thrombolysis prognosis.Individual clinical indicators and a combined predictive model were constructed,and their performances were evaluated using receiver operating characteristic curve analysis.The optimal cutoff values for individual and combined predictors were determined by maximizing the Youden index.Comparative analysis of individual clinical indicator and combined models were performed to assess predictive efficacy.Results Among 404 acute cerebral infarction patients treated with intravenous thrombolysis,282 achieved favorable outcomes while 122 had poor outcomes.FVH positivity was observed in 202 cases.(1)Inter-rater reliability:radiologists demonstrated substantial agreement in FVH scoring(Kappa=0.757,95%CI 0.702-0.812,P＜0.01).(2)Univariate analysis showed that significant intergroup differences were found in pre-thrombolysis laboratory values:white blood cell(9.21[7.37,10.85]×109/L vs.7.30[5.83,8.62]×109/L,Z=-7.064,P＜0.01),neutrophils(7.25[5.27,9.02]×109/L vs.4.93[3.81,6.20]×109/L,Z=-8.173,P＜0.01),lymphocytes(1.40[0.92,1.74]×109/L vs.1.57[1.16,1.99]×109/L,Z=-3.380,P=0.001),glucose(7.00[6.30,8.70]mmol/L vs.6.60[5.80,7.80]mmol/L,Z=-2.913,P=0.004),uric acid(318.50[257.50,392.00]μmol/L vs.340.50[282.00,416.25]μmol/L,Z=-2.168,P=0.030),and NIHSS score(8[5,10]vs.3[1,5],Z=-9.286,P＜0.01),FVH score(1[0,2]vs.0[0,1],Z=-4.036,P＜0.01).(3)Collinearity testing excluded white blood cell(VIF=20.561,margin of tolerance=0.049)due to high correlation with neutrophils(VIF=20.303,margin of tolerance=0.049).The rest variables with significant statistic difference in the univariate Logistic analysis were incorporated into the multivariable Logistic regression analysis,high neutrophils(OR,1.489,95%CI 1.314-1.688,P＜0.01),NIHSS score(OR,1.306,95%CI 1.213-1.407,P＜0.01),FVH score(OR,1.976,95%CI 1.398-2.794,P＜0.01)pre-thrombolysis were the independent risk factors for the poor outcome of acute cerebral infarction patients with intravenous thrombolysis treatment.(4)Predictive performance:the optimal cutoff values of FVH score,NIHSS score and neutrophils pre-thrombolysis was 1.000,5.000 and 6.586×109/L respectively,and their area under the curve(AUC)were 0.616(95%CI 0.566-0.663;55.7%sensitivity,63.1%specificity),0.789(95%CI 0.746-0.828;77.7%sensitivity,71.3%specificity),0.756(95%CI 0.711-0.797;80.9%sensitivity,59.8%specificity),respectively;the cutoff value of combined model was 0.786(AUC=0.863;95%CI 0.825-0.895,71.6%sensitivity,88.5%specificity).Conclusion The high FVH score,NIHSS score and neutrophil count pre-thrombolysis were independent predictors of poor prognosis of intravenous thrombolysis in patients with acute cerebral infarction,and the model combining the aforementioned predictors has enhanced predictive value.

With the advent of era of tumor immunotherapy,effect of intestinal flora in immunotherapy has attracted much attention.A large number of studies have confirmed the role of traditional Chinese medicine in regulating intestinal flora.Based on this,this paper discusses and summarizes the effect and mechanism of traditional Chinese medicine intervention on tumor immune checkpoint inhibitors(ICIs)treatment,providing a theoretical basis for in-depth understanding of the correlation between traditional Chinese medicine,intestinal flora and immunotherapy,and also providing new ideas for improving the efficacy of tumor immunotherapy and reducing immune-related adverse reactions.

The concept of amplification feedback pathways represents an intersection between electronics and control theory,involving both amplification and feedback processes.It reveals the dynamic evolution mechanisms of systems under the combined influence of these two processes.In Traditional Chinese Medicine(TCM),Chest Bi syndrome is considered a"ben xu biao shi"condition,with its primary pathology located in the heart and closely related to other organs such as the liver,spleen and kidneys.This article focuses on the interrelationship between organ dysfunction and the imbalance of the Five Elements Theory.By applying amplification feedback theory and models,the study constructs and analyzes single-stage amplification feedback pathways involving the heart,liver and kidneys,as well as double-stage amplification feedback pathways involving the heart,liver,kidneys and spleen,in the context of multifactorial interactions such as heart and kidney Yang deficiency,Qi stagnation in the heart and chest,and spleen-stomach dysfunction.Particular emphasis is placed on analyzing the phenomena of deep feedback and self-excited oscillation,and specific formulas and clinical evidence are used to validate the analysis results,clarifying the role of relevant organ function changes in the pathogenesis of Chest Bi syndrome.The article aims to provide new insights into the complex pathogenesis of refractory diseases from a control theory perspective,offering new directions for modernizing TCM research with digital technology and theoretical support for future simulation-based digital systems guided by TCM theory.

Objective To analyse the efficacy of Gao Mo therapy in the treatment of aromatase inhibitor-related osteoarticular symptoms in breast cancer patients.Methods A total of 80 breast cancer patients with aromatase inhibitor-related osteoarticular symptoms were selected from the breast clinic of a Tier-IIIA hospital in Guangdong Province between January and August 2024.The patients were divided into an intervention group and a control group according to the random number table,with 40 patients per group.Patients in the control group received routine nursing care,while the patients in the intervention group received Gao Mo therapy for 4 weeks based on the intervention of the control group.The two groups were compared with in terms of pain level,index of knee osteoarthritis,and quality of life of the patients with breast cancer before intervention and at 1st,2nd and 4th weeks after intervention.Results Before the intervention,the two groups presented no significant differences in scores of pain assessment,knee osteoarthritis index and quality of life(P>0.05).Analysis of variance for repeated measures showed that the main effects of time and group as well as the interaction effect,were statistically significant in scores of pain assessments in both groups(both P<0.05).The main effects of time and the interaction effect were statistically significant in scores of knee osteoarthritis index and quality of life assessments at different time points(both P<0.05),but there was no statistically significant difference in the main effect between groups(both P>0.05).After 4 weeks of intervention,the intervention group demonstrated significantly lower scores in knee function and pain assessments with a significantly higher scores in the total quality of life assessment in comparison with those of the control group(all P<0.05).Conclusion Gao Mo therapy can mitigate the aromatase inhibitor-related osteoarticular symptoms in breast cancer patients,enhance the function of knees,and improve the quality of life of the patients with breast cancer.

BACKGROUND:Human endometrial mesenchymal stem cells can directly repair the damaged endometrium,promote angiogenesis,and restore the morphological structure of the uterus.However,after the direct injection of stem cells into the damaged endometrium,the cell survival rate is low,the retention time is short,and the repair effect is limited.OBJECTIVE:To observe the effect of polycaprolactone-hyaluronic acid electrospinning membrane combined with human endometrial mesenchymal stem cells on endometrial injury in rats.METHODS:(1)Cell experiment:Human endometrial mesenchymal stem cells were extracted by collagenase digestion method.Polycaprolactone-hyaluronic acid electrospinning membrane was prepared by electrospinning technology.The human endometrial mesenchymal stem cells were inoculated on polystyrene culture plate and polycaprolactone-hyaluronic acid electrospinning membrane.The proliferation and adhesion of the cells were observed by DNA quantitative analysis,WST-1 cell activity test,phalloidin staining,and scanning electron microscopy.The mRNA expressions of CD90 and Meflin in electrospun membrane were detected by qRT-PCR.(2)Animal experiments:27 female SD rats in estrus were selected to establish uterine adhesion model by mechanical scratching method and randomly divided into three groups with nine rats in each group:The blank control group did not receive any treatment;the control group was implanted with polycaprolacton-hyaluronic acid electrospinning membrane;the experimental group was implanted with polycaprolacton-hyaluronic acid electrospinning membrane/human endometrial mesenchymal stem cell mesh.Samples were collected at 3,7,and 14 days after surgery.Hematoxylin-eosin staining was used to observe the morphological structure of uterus and the number of glands.qRT-PCR and immunofluorescence staining were used to observe the expression of CD31 and vascular endothelial growth factor in uterine tissue.RESULTS AND CONCLUSION:(1)Cell experiment:Compared with polystyrene culture plate,polycaprolactone-hyaluronic acid electrospinning membrane could promote the proliferation and adhesion of human endometrial mesenchymal stem cells.Polycaprolactone-hyaluronic acid electrospinning membrane supported the expression of CD90 and Meflin genes of human endometrial mesenchymal stem cells.(2)Animal experiments:Hematoxylin-eosin staining showed that polycaprolactic-hyaluronic acid electrospinning membrane/human endometrial mesenchymal stem cell patch could promote the recovery of endometrial morphological structure after injury.The endometrial thickness and number of gland on day 14 after surgery were higher than those in blank control group and control group(P<0.05).qRT-PCR and immunofluorescence staining showed that the mRNA and protein expressions of CD31 and vascular endothelial growth factor in the experimental group were higher than those in the blank control group and the control group at 7 and 14 days after surgery(P<0.05).(3)The results showed that polycaprolacton-hyaluronic acid electrospinning membrane could improve the survival rate of stem cells and prolong the contact time between stem cells and the damaged tissue,and the composite transplantation of the two could better repair the damaged endometrial tissue.

Objective To explore the diagnostic value of 18F-fluorodeoxyglucose(FDG)PET/CT in primary pulmonary enteric adenocarcinoma.Methods The clinical and imaging data of 9 patients with primary pulmonary enteric adenocarcinoma who under-went 18F-FDG PET/CT examination were retrospectively analyzed,including lesion distribution,morphology,maximum standardized uptake value(SUVmax),clinical symptoms and signs,gastroscopy finding,puncture pathological results,and serum tumor markers[carbohydrate antigen 72-4(CA72-4),cytokeratin 19 fragment antigen 21-1(CYFRA21-1),carcinoembryonic antigen(CEA),carbo-hydrate antigen 199(CA199)].Results Pathological examination confirmed a diagnosis of primary pulmonary enteric adenocarcinoma after excluding gastrointestinal primary tumors through clinical evaluation.In all nine patients,18F-FDG PET/CT examination did not reveal any evidence of digestive system malignancies,and gastrointestinal microscopy was negative.Primary lesions were observed as masses or nodular types in 6 cases(5 in the left lung and 1 in the right lung),while 3 cases exhibited diffuse bilateral pulmonary involvement(manifested as multiple patchy opacities,nodules,ground-glass opacities,and consolidations).All pulmonary primary lesions showed increased 18F-FDG uptake,with SUVmax ranging from 2.7 to 12.8,mean 8.6±3.7.The six masses-or nodular-type primary lesions showed maximum diameters ranging from 2.1 to 10.5 cm,mean(5.23±3.06)cm.Four cases demonstrated hilar and mediastinal lymph node metastases,intrapulmonary metastases,and distant metastases,while 1 case showed only distant metastasis.Elevated levels of serum tumor markers were observed as follows:CA72-4 in 7 cases(10-273.3 U/mL),CEA in 7 cases(5-147.4 ng/mL),CA199 in 6 cases(31.22-4 364 U/mL),and CYFRA21-1 in 5 cases(8.31-99.7 ng/mL).Conclusion When pathological biopsy of a pulmonary lesion suggests primary pulmonary enteric adenocarcinoma after excluding gastrointestinal primary tumors,and 18F-FDG PET/CT shows no gastrointestinal masses,this may support the diagnosis of primary pulmonary enteric adenocarcinoma.