ObjectiveTo investigate the demyelination induced by Angiostrongylus cantonensis （AC） infection in the brain of Balb/c mice and analyze the untargeted metabolomic changes in the corpus callosum， aiming to elucidate the underlying mechanisms. MethodsBalb/c mice were randomly assigned to a control group （n=6） and an infection group （n=6）. The infection group was orally administered 30 third-stage larvae of AC， while the control group received an equal volume of saline. Body weight， visual function， and behavioral scores were measured on post-infection 3， 6， 9， 12， 15， 18， and 21 days to assess neurological alterations. After 21 days， brain tissues were harvested for immunofluorescence staining， hematoxylin-eosin （HE） staining， and transmission electron microscopy to examine morphological changes in brain myelin and retina. Metabolomics analysis was performed， and differential metabolites were identified using volcano plots and heatmaps. The distribution of fold changes and bar charts were used to profile the key metabolites. These differential metabolites were then subjected to Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and regulatory network analysis. ResultsOn the 9th day after AC infection， Balb/c mice showed a decline in neurological behavioral scores （P<0.05）. By day 15， visual scores decreased （P<0.05）， and by day 21， significant weight loss （P＜0.001） and mortality were observed. Concurrently， transmission electron microscopy and immunofluorescence staining revealed significant myelin damage in the corpus callosum and a marked reduction in oligodendrocytes （P<0.001）. HE staining showed severe retinal ganglion cell damage. Metabolomic analysis revealed that glycerophospholipids were the most abundant differential metabolites， with steroids and sphingolipids being relatively less abundant. Cholesteryl ester CE （20：2） was significantly upregulated （P<0.001）， while phosphatidylmethanol （18：0_18：1） was significantly downregulated （P<0.01）. KEGG enrichment and regulatory network analyses demonstrated that the differential metabolites were mainly enriched in metabolic pathways like steroid biosynthesis， bile secretion， and cholesterol metabolism， and were involved in key metabolic pathways such as sphingolipid metabolism， neural signal regulation， and glycerophospholipid metabolism. ConclusionsAC infection affects the metabolic state of mice via multiple pathways， modifying the levels of metabolites crucial for myelination and myelin stability. Demyelination may be closely linked to the disruption of these key metabolic pathways， particularly the dysregulation of cholesterol and sphingolipid metabolism， potentially playing a central role in demyelination onset. Furthermore， alterations in phospholipid metabolism and abnormal nerve signaling regulation may exacerbate myelin damage.

OBJECTIVE To explore the protective effect of marein against alcoholic fatty liver （AFL） and its potential mechanisms. METHODS AFL mice model was established with strong wine by gavage. The mice were randomly divided into normal control group （n＝9， 0.5% sodium carboxymethyl cellulose solution）， model group （n＝10， 0.5% sodium carboxymethyl cellulose solution） and marein 75 and 150 mg/kg groups （n＝9）. Mice were given relevant medicine intragastrically， once a day， for consecutive 30 days. After the last medication， the levels of triglyceride （TG）， malondialdehyde （MDA）， and superoxide dismutase （SOD） in liver tissue were determined， and hepatic histopathological changes of liver tissue were observed； the protein expression levels of peroxisome proliferator-activated receptor α （PPARα）， carnitine palmitoyltransferase-1 （CPT-1）， and diacylglycerol acyltransferase （DGAT） were determined in liver tissue. BRL hepatocytes injury model was induced by ethanol combined with ferrous sulfate and oleic acid； after treatment with 3， 6 and 12 μmol/L of marein for 24 h， the distribution of lipid droplets， the levels of TG， MDA and SOD and protein expressions of PPARα， CPT-1 and DGAT in hepatocytes were examined. After pretreatment with MK886 （PPARα inhibitor， 10 μmol/L），modeled hepatocytes were treated with 12 μmol/L of marein for 24 h， and the protein expressions of PPARα， CPT-1 and DGAT were determined. RESULTS As the results showed in vivo， compared with the model group， after treatment with 75 and 150 mg/kg of marein， the degree of steatosis was significantly reduced， and the levels of TG and MDA and protein expression of DGAT were significantly decreased（P＜0.05 or P＜0.01）； the levels of SOD， protein expressions of PPARα and CPT-1 were significantly increased（P＜0.05 or P＜0.01）. As the results showed in vitro， after treatment with 3， 6 and 12 μmol/L of marein， the lipid accumulation of hepatocytes was significantly inhibited， and the levels of TG and MDA， protein expression of DGAT were significantly decreased（P＜0.05 or P＜0.01）， while the levels of SOD， protein expressions of PPARα and CPT-1 were significantly increased（P＜0.05 or P＜0.01）. After MK886 pretreatment， the effects of marein on the above protein expressions were abolished. CONCLUSIONS Marein might exert a protective effect against AFL. The mechanisms might be related to inhibiting oxidative stress-mediated injury and improving PPARα-mediated lipid metabolism signaling pathway.

Objective To investigate the effects of treatment with nicorandil after Percutaneous Coronary Intervention(PCI)in patients with Acute Coronary Syndrome(ACS)on inflammation-related markers,and to assess its effects on vascular endothelial function.Methods Sixty-six ACS patients who underwent PCI in the Department of Cardiovascular Medicine of the Second Affiliated Hospital of Dalian Medical University from August 2022 to January 2023 were used as the study sample,and were divided into the control group and the experimental group according to the method of completely randomized design,with 33 cases in each group.The control group was treated with conventional therapy,and the experimental group was treated with nicorandil.Inflammatory indexes,homocysteine(Hcy)and adverse reactions in serum were compared between the two groups.Results After nicorandil treatment,the levels of postoperative inflammation-related factors in the control group were higher than that in the experimental group,and the difference was statistically significant(P<0.05);The levels of Hcy after nicorandil treatment were lower than that in the control group,and the difference was statistically significant(P<0.05);and the rate of adverse reactions in the experimental group was higher than that in the control group,and there was no statistical difference(P>0.05).Conclusion Nicorandil application in elderly ACS patients after PCI has a definite efficacy,can optimize the vascular-related inflammatory indexes,reduce homocysteine levels to improve coronary vascular endothelial function,and is suitable for further promotion.

Objective:To study correlation between related carotid ultrasound parameters and severity of coronary atherosclerosis(AS).Methods:According to number of diseased coronary arteries,a total of 116 patients with cor-onary heart disease diagnosed by coronary angiography in our hospital were divided into single vessel coronary dis-ease group(n=38,single group),double vessel coronary disease group(n=39,double group)and ≥3 vessel coro-nary disease group(n=39,multiple group).Another 41 healthy subjects were simultaneously regarded as healthy control group.General clinical data and carotid ultrasound parameters were compared among all groups,and corre-lation among them and AS severity was analyzed.Results:Compared with healthy control group,there were signifi-cant rise in levels of total cholesterol(TC),triglycerides(TG)and low density lipoprotein cholesterol(LDL-C),carotid intima-media thickness(IMT)and Crouse score in single,double and multiple groups,and significant re-ductions in plaque echo gray-scale median(GSM)in double and multiple groups.Compared with single group,there were significant rise in levels of TG and LDL-C,Gensini score and Crouse score in double and multiple groups and TC level in multiple group,and significant reduction in plaque echo GSM in multiple group.Compared with double group,there were significant rise in TC level,Gensini score and Crouse score,and significant reduction in plaque echo GSM in multiple group(P＜0.05 or＜0.01).Pearson correlation analysis indicated that Gensini score was significant positively correlated with Crouse score in these patients(r=0.580,P=0.001).Spearman correla-tion analysis indicated that IMT was significant positively correlated with number of diseased coronary arteries(r=0.582,P=0.001),and plaque echo GSM was significant inversely correlated with it(r=-0.518,P=0.001)in these patients.Conclusion:Related carotid ultrasound parameters are significantly correlated with severity of coro-nary atherosclerosis.

Objective:To analyze retinal vascular parameters and distribution characteristics in Chinese population via the fully automated quantitative measurement of retinal vascular morphological parameters based on artificial intelligence technology.Methods:A cross-sectional study was performed.A total of 1 842 patients without fundus diseases who visited Beijing Tongren Hospital from January 2011 to December 2021 were included.Standardized questionnaires, blood draws and ophthalmologic examinations of enrolled subjects were conducted.Color fundus photographs centered on the optic disk of one eye of patients were collected, and a deep learning-based semantic segmentation network ResNet101-Unet was used to construct a vascular segmentation model for fully automated quantitative measurement of retinal vascular parameters.The main measurement indexes included retinal vascular branching angle, vascular fractal dimension, average vascular caliber, and average vascular tortuosity.To compare different retinal parameters between sexes, the correlation between the above parameters and ocular factors such as best corrected visual acuity, intraocular pressure, and axial length, as well as systemic factors such as sex, age, hypertension, diabetes mellitus, and cardiovascular disease was analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.20001220). Written informed consent was obtained from each subject.Results:The model established in this study achieved an accuracy over 0.95 for both vascular and optic disk segmentation.The vascular branching angle, vascular fractal dimension, average vascular caliber, and average vascular tortuosity were (51.023±11.623)°, 1.573(1.542, 1.592), 64.124(60.814, 69.053)μm, (0.001 062±0.000 165)°, respectively.Compared with females, males had larger vascular branching angle, smaller average vascular caliber and smaller vascular tortuosity, and the differences were statistically significant (all at P<0.05). The average vascular caliber increased by 1.142 μm in people with cardiovascular disease compared to people without cardiovascular disease ( B=1.142, P=0.029, 95% CI: 0.116-2.167). The average vascular tortuosity was positively correlated with hypertension ( B=3.053×10 -5, P=0.002, 95% CI: 1.167×10 -5-4.934×10 -5) and alcohol consumption ( B=1.036×10 -5, P=0.014, 95% CI: 0.211×10 -5-1.860×10 -5) and negatively correlated with hyperlipidemia ( B=-2.422×10 -5, P=0.015, 95% CI: -4.382×10 -5-0.462×10 -5). For each 1-mm increase in axial length, there was a decrease of 0.004 in vessel fractal dimension ( B=-0.004, P<0.001, 95% CI: -0.006--0.002), a decrease of 0.266 μm in the average vessel caliber ( B=-0.266, P=0.037, 95% CI: -0.516--0.016), and a decrease of -2.45×10 -5° in the average vessel tortuosity ( B=-2.45×10 -5, P<0.001, 95% CI: -0.313×10 -5--0.177×10 -5). For each 1.0 increase in BCVA, there was an increase of 3.992° in the vascular branch angle ( B=3.992, P=0.004, 95% CI: 1.283-6.702), an increase of 0.090 in vascular fractal dimension ( B=0.090, P<0.001, 95% CI: 0.078-0.102) and a decrease of 14.813 μm in the average vascular diameter ( B=-14.813, P<0.001, 95% CI: -16.474--13.153). Conclusions:A model for retinal vascular segmentation is successfully constructed.Retinal vessel parameters are associated with sex, age, systemic diseases, and ocular factors.

Objective To explore the effects of different fractionation doses,fractionation methods,and other related parameters on the peripheral blood lymphocyte count of patients with liver cancer receiving CyberKnife radiotherapy.Methods The clinical data of 90 patients with liver cancer receiving CyberKnife radiotherapy in our hospital were retrospectively analyzed.The peripheral blood lymphocyte counts of patients 1 week before CyberKnife radiotherapy and 1 week,1 month and 3 months after treatment were determined.The effects of different prescribed doses,fractionation doses and numbers of fractionations on the peripheral blood lymphocyte count were analyzed.Results The peripheral blood lymphocyte counts of patients with different prescribed doses,fractionation doses and fractionation methods after CyberKnife treatment decreased to varying degrees compared with those 1 week before treatment(P<0.05).The peripheral blood lymphocyte counts of patients in the groups with≤5 fractionations and fractionation dose>7 Gy were significantly higher than those of patients in the groups with>5 fractionations and the fractionation dose≤7 Gy,respectively(P<0.05).There was no significant difference in peripheral blood lymphocyte counts between patients with different prescribed doses before and after CyberKnife treatment(P>0.05).Conclusion CyberKnife in the treatment of liver cancer with≤5 ractionations and a fractionation dose of>7 Gy is more beneficial to alleviate the decrease of lymphocyte count caused by Cyberknife treatment.

Purpose To explore the diagnostic efficiency of ultrasound(US)combined with contrast-enhanced ultrasound(CEUS)in breast lesions and to analyze the related factors affecting the diagnostic accuracy.Materials and Methods From January 2022 to February 2023,the clinical data and ultrasound images of 784 patients who underwent breast US and CEUS examination with definite pathological results were retrospectively collected in the First Medical Center of the PLA General Hospital.The diagnostic efficacy of US combined with CEUS in benign and malignant breast lesions was analyzed,respectively.The independent risk factors for diagnostic errors were analyzed via Logistic regression.Results The sensitivity,specificity and accuracy of US combined with CEUS in the diagnosis of benign and malignant breast lesions were 89.2%,84.4%and 88.7%,respectively.The area under the receiver operating characteristic curve was 0.932.The results of multivariate Logistic regression analysis showed that the diagnosis error rate increased when the lesions were non-mass type(odds ratio,OR=1.927,P=0.047),complex cystic and solid(OR=3.729,P=0.000),and high-enhanced CEUS(OR=1.937,P=0.023),while the diagnosis error rate decreased when the lesions were large(OR=0.688,P=0.004)and with US-detect suspicious lymph node(OR=0.143,P=0.011).Conclusion When the breast lesions are non-mass type,complex cystic and solid lesions and hyper-enhancement,the diagnosis error rate of US combined with CEUS increased.It is necessary to further explore the enhancement patterns of different lesions.

Purpose To explore the correlation between phosphatidylinositol 3 kinase/serine-threonine kinase(PI3K/AKT)signaling pathway and elastic characteristics of breast lesions.Materials and Methods A total of 115 breast lesions were prospectively analyzed in 114 patients who underwent surgery from May 2021 to May 2022 at Chinese PLA General Hospital.Ultrasound and shear wave elastography were performed preoperatively.Immunohistochemical staining was used to detect the expression of PI3K/AKT protein levels in the tissue specimens,and the correlation between the staining results and the elastic parameters of shear wave elastography was analyzed.Results Surgical pathology revealed benign breast lesions in 50 cases and malignant lesions in 65 cases(25 cases with axillary lymph node metastasis).The maximum modulus of elasticity(F=40.47),the average modulus of elasticity(F=45.11),the ratio of elasticity of the lesion to that of the surrounding tissue(F=48.98),the detection rate of"hard ring sign"(χ2=62.25),the expression level of PI3K/p-PI3K(F=15.19,58.95)and AKT/p-AKT(F=46.94,74.21)were found in benign and malignant lesions without axillary lymph node metastasis,malignant lesions with axillary lymph node metastasis(all P<0.05).The expression levels of PI3K/p-PI3K and AKT/p-AKT were positively correlated with the maximum elastic modulus value,the mean elastic modulus value,and the ratio of elasticity of the lesion to the surrounding tissues(r=0.475,0.475,0.451;r=0.533,0.540,0.542;r=0.371,0.402,0.445;r=0.482,0.455,0.545,all P<0.05).Conclusion The expression level of PI3K/AKT in breast lesions is correlated with elastic characteristics,suggesting that it plays an important role in the regulation of elastic characteristics of breast lesions.

Objective To observe the effects of Bushen Zhuyun Prescription on regulating mitochondrial function and endometrial angiogenesis;To explore its mechanism of improving endometrial receptivity.Methods The mouse model of controlled ovarian hyperstimulation(COH)was established,and the mice were randomly divided into normal group,model group,and Bushen group,with 20 mice in each group.Bushen group received Bushen Zhuyun Prescription for gavage for 11 d,and the normal group and model group received normal saline for gavage.The number of embryo implantation was counted,the endometrial morphology was observed by HE staining,α-smooth muscle actin(α-SMA)expression was observed by immunofluorescence staining.Human endometrial microvascular endothelial cells(HEMECs)were cultured in vitro,they were divided into control group,VEGFA group,Bushen group and VEGFA + Bushen group,and were intervened with VEGFA and/or Bushen Zhuyun Prescription medicated serum.The activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ,the content of ATP,the expression of PCNA and Caspase-3 were detected.Results Animal experiment showed that,compared with the normal group,the number of embryo implantation in model group significantly decreased(P<0.05),α-SMA protein expression in endometrial tissue significantly decreased(P<0.05);compared with the model group,the number of embryo implantation in Bushen group significantly increased(P<0.05),α-SMA protein expression in endometrial tissue significantly increased(P<0.05).Cell experiment showed that,Bushen Zhuyun Prescription medicated serum could increase the activity of mitochondrial respiratory chain complexes Ⅰ-Ⅳ and ATP content in HEMECs,promote PCNA protein expression,and inhibit Caspase-3 protein expression(P<0.05,P<0.01).Conclusion Bushen Zhuyun Prescription can promote endometrial angiogenesis through improving mitochondrial function.

Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.