ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation， and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group， model group， and Diwu Yanggan Capsule group using a random number table， with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage， and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention； DNA methylation chips were used to analyze the change in DNA methylation in liver tissue， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were used for data analysis. In addition， the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB， ADCK2， ERLIN2， SEMA3B， and TPH2 in the liver tissue of rats， and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups， while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group， the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group， the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes， and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation， apoptosis， and microenvironment regulation， such as the calcium ion signaling pathway， the cAMP signaling pathway， and the extracellular factor signaling pathway. Compared with the model group， the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene （P<0.05） and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes （all P<0.05）. Compared with the model group， the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 （all P<0.05）. ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

Objective:To compare the effects of different automatic normal tissue objective(NTO)weights(WNTO)of Eclipse planning system on intensity modulated radiation therapy(IMRT)of fixed field for abdominal tumor.Methods:Twenty patients with rectal cancer and twenty patients with cervical cancer who received radiotherapy in The Second People's Hospital of Huludao from September 2022 to January 2024 were selected.5 groups of different plans[WNTO20,40,60,80 and 100]were respectively formulated for each patient.Among of them,the WNTO20 plan was control group,and other 4 groups were respectively WNTO40 group,WNTO60 group,WNTO80 group and WNTO100 group.Then,the differences in dosimetry and monitor units(MU)among 5 groups of plans were compared.Results:In the WNTO 80 and 100 groups of patients with rectal cancer,the conformation index(CI)values of target regions of them were respectively 1.02±0.04 and 1.00±0.03,all of which approached to 1,and the CI values of two groups were lower than that of control group,and the differences were statistically significant(t=15.986,18.422,P<0.05).The homogeneity index(HI)of WNTO 80 and 100 groups were respectively 0.09±0.12 and 0.10±0.14,which were higher than that of control group,and the differences were statistically significant(t=-1.371,-1.463,P<0.05).The 52Gy dose volume(Vmax52)of small intestine of the two groups were respectively(4.48±14.49)and(4.77±10.47)cm3,which were higher than that of control group,and the differences were statistically significant(t=-1.360,-2.005,P<0.05).The 30 Gy dose volume percentage(V30 Gy)values of the right femoral heads of the two groups were respectively(12.28±4.57)%and(10.96±4.17)%,which were lower than that of control group,and the differences were statistically significant(t=6.893,6.75,P<0.05).The 30 Gy dose volume percentage(V30 Gy)values of the left femoral head of the two groups were respectively(11.57±4.41)%and(10.17±3.78)%,which were lower than that of control group,and the differences were statistically significant(t=6.782,5.963,P<0.05).The MU value of WNTO100 group was(1254±93)MU,which was higher than that of control group,and the difference was statistically significant(t=-3.741,P<0.05).In the WNTO 80 and 100 groups of patients with cervical cancer,the CI values of target regions of them were respectively 1.03±0.32 and 1.02±0.03,all of which approached to 1,and the CI values of the two groups were lower than those of control group,and the differences were statistically significant(t=20.069,19.475,P<0.05).The HI values of them were respectively 0.07±0.05 and 0.08±0.01,which were higher than that of control group,and the differences were statistically significant(t=-12.445,-19.478,P<0.05).The V30 Gy values of the right femoral heads of the two groups were respectively(16.11±4.71)%and(14.90±4.56)%,which were lower than that of control group,and the differences were statistically significant(t=7.875,8.020,P<0.05).The V30 Gy values of the left femoral head of the two groups were respectively(15.21±3.71)%and(13.93±3.77)%,which were lower than that of control group,and the differences were statistical significance(t=7.617,7.436,P<0.05).The Vmax52 of small intestine of the two groups were respectively(0.82±1.10)and(4.47±8.81)cm3,which were higher than that of control group,and the difference was statistically significant(t=-2.985,-2.388,P<0.05).Conclusion:The WNTO80 is recommended for IMRT plan of radiotherapy on abdominal tumor,which can more quickly and better meet the assessment conditions of IMRT plan.

Objective To evaluate the value of 68Ga-DOTATATE and 18F-FDG PET/CT imaging in staging and treatment decision for gastroenteropancreatic neuroendocrine neoplasms(GEP-NEN).Methods This retrospective analysis was conducted in 49 patients with GEP-NEN undergoing 18F-FDG and 68Ga-DOTATATE PET/CT imaging at our hospital from August,2020 to March,2023,including 34 newly diagnosed patients and 15 patients with recurrence or metastasis after treatment.GEP-NEN were classified into G1,G2,and G3 neuroendocrine tumors(NET)and neuroendocrine carcinomas(NEC)based on pathological typing.The detection efficiency were classified into 4 patterns based on the number of positive tumor lesions detected by the two tracers:68Ga-DOTATATE>18F-FDG(A);68Ga-DOTATATE=18F-FDG(B);68Ga-DOTATATE<18F-FDG(C);and complementation(D).The value of dual-modality imaging in staging and treatment decision were evaluated by visual analysis.Results In the 49 patients with GEP-NEN,68Ga-DOTATATE PET/CT was superior to 18F-FDG PET/CT for detecting systemic tumor lesions(P<0.001)and more sensitive for detecting primary/recurrent lesions,lymph node metastasis,liver metastasis,and bone metastasis(P<0.05),while 18F-FDG PET/CT had higher detection rates for lung metastasis and peritoneal metastasis(P<0.05).In terms of the detection efficiency,Pattern A was found in 46.9%(23/49)patients,Pattern B in 38.8%(19/49),Pattern C in 12.2%(6/49),and Pattern D in 2.0%(1/49).The complementary value of 18F-FDG PET/CT to 68Ga-DOTATATE PET/CT was 0%in G1 NET patients(0/13),8.3%in G2 NET patients(2/24),50%in G3 NET patients(3/6),and 33.3%in NEC patients(2/6).12.2%(6/49)of the patients had their staging confirmed or changed due to additional lesions detected by 18F-FDG PET/CT imaging,resulting subsequently in establishment or adjustment of their treatment plans.Conclusion 68Ga-DOTATATE PET/CT imaging should be the primary choice for GEP-NEN patients.Additional 18F-FDG PET/CT imaging can potentially improve precision of staging and treatment decision-making for G2,G3 and NEC patients but provides virtually no clinical benefits for G1 NET patients.

Objective:To compare the effects of different automatic normal tissue objective(NTO)weights(WNTO)of Eclipse planning system on intensity modulated radiation therapy(IMRT)of fixed field for abdominal tumor.Methods:Twenty patients with rectal cancer and twenty patients with cervical cancer who received radiotherapy in The Second People's Hospital of Huludao from September 2022 to January 2024 were selected.5 groups of different plans[WNTO20,40,60,80 and 100]were respectively formulated for each patient.Among of them,the WNTO20 plan was control group,and other 4 groups were respectively WNTO40 group,WNTO60 group,WNTO80 group and WNTO100 group.Then,the differences in dosimetry and monitor units(MU)among 5 groups of plans were compared.Results:In the WNTO 80 and 100 groups of patients with rectal cancer,the conformation index(CI)values of target regions of them were respectively 1.02±0.04 and 1.00±0.03,all of which approached to 1,and the CI values of two groups were lower than that of control group,and the differences were statistically significant(t=15.986,18.422,P<0.05).The homogeneity index(HI)of WNTO 80 and 100 groups were respectively 0.09±0.12 and 0.10±0.14,which were higher than that of control group,and the differences were statistically significant(t=-1.371,-1.463,P<0.05).The 52Gy dose volume(Vmax52)of small intestine of the two groups were respectively(4.48±14.49)and(4.77±10.47)cm3,which were higher than that of control group,and the differences were statistically significant(t=-1.360,-2.005,P<0.05).The 30 Gy dose volume percentage(V30 Gy)values of the right femoral heads of the two groups were respectively(12.28±4.57)%and(10.96±4.17)%,which were lower than that of control group,and the differences were statistically significant(t=6.893,6.75,P<0.05).The 30 Gy dose volume percentage(V30 Gy)values of the left femoral head of the two groups were respectively(11.57±4.41)%and(10.17±3.78)%,which were lower than that of control group,and the differences were statistically significant(t=6.782,5.963,P<0.05).The MU value of WNTO100 group was(1254±93)MU,which was higher than that of control group,and the difference was statistically significant(t=-3.741,P<0.05).In the WNTO 80 and 100 groups of patients with cervical cancer,the CI values of target regions of them were respectively 1.03±0.32 and 1.02±0.03,all of which approached to 1,and the CI values of the two groups were lower than those of control group,and the differences were statistically significant(t=20.069,19.475,P<0.05).The HI values of them were respectively 0.07±0.05 and 0.08±0.01,which were higher than that of control group,and the differences were statistically significant(t=-12.445,-19.478,P<0.05).The V30 Gy values of the right femoral heads of the two groups were respectively(16.11±4.71)%and(14.90±4.56)%,which were lower than that of control group,and the differences were statistically significant(t=7.875,8.020,P<0.05).The V30 Gy values of the left femoral head of the two groups were respectively(15.21±3.71)%and(13.93±3.77)%,which were lower than that of control group,and the differences were statistical significance(t=7.617,7.436,P<0.05).The Vmax52 of small intestine of the two groups were respectively(0.82±1.10)and(4.47±8.81)cm3,which were higher than that of control group,and the difference was statistically significant(t=-2.985,-2.388,P<0.05).Conclusion:The WNTO80 is recommended for IMRT plan of radiotherapy on abdominal tumor,which can more quickly and better meet the assessment conditions of IMRT plan.

This study aims to investigate the effect of Lactiplantibacillus plantarum LP12 on obe-sity prevention.In our study,Lactiplantibacillus plantarum LP12 was added to the diet for feed-ing,and the blood biochemistry status of rabbit,as well as the antioxidant effect of serum and liver samples were analyzed by determining the body weight change and feed intake of Japanese White rabbits.The changes in colony structure and abundance were also analyzed by 16S rDNA sequen-cing.The results showed that supplementation of Lactiplantibacillus plantarum LP12 inhibits weight gain,decreases serum glucose and ALT levels,and increases SOD activity in the liver.16S RNA gene sequencing analysis showed that the addition of Lactiplantibacillus plantarum LP12 increases the abundance of Bacteroidetes and Desulfovibrioides at the phylum level,and the supple-mentation of Lactiplantibacillus plantarum LP12 increases the abundance of Muribaculaceae at the genus level.Predictive analysis of microbiota function revealed that the supplementation of Lactiplantibacillus plantarum LP12 positively regulated iron-sulfur clusters and Zn-dependent proteases.In conclusion,the addition of Lactiplantibacillus plantarum effectively inhibits weight gain in Japanese White rabbits,enhances the antioxidative activity of the liver,and induces altera-tions in the gut microbiota composition of these rabbits.These findings lay an experimental foun-dation for further exploring the mechanisms by which Lactobacillus plantarum LP12 exerts its preventive effects against obesity and promotes metabolic health.

Objective To explore the relationship between triglyceride-glucose(TyG)index and hypertension in patients with cerebral hemorrhage.Methods A total of 1718 patients with cere-bral hemorrhage admitted to our hospital from January,2013 to May,2023 were enrolled in this study.According to the TyG index quartile,437 cases were assigned into Q1 group(≤8.375),424 cases into Q2 group(TyG index 8.376～8.737),429 cases into Q3 group(TyG index 8.738～9.087),and 428 cases into Q4 group(≥9.088).The general clinical data were compared in the four groups.Logistic regression analysis was used to study the correlation between TyG index and hy-pertension.Results There were significant differences among the four groups in terms of age,hy-pertension,diabetes,SBP,DBP,TC,TG,HDL-C,LDL-C,FBG,glycated hemoglobin and TyG in-dex(P＜0.05,P＜0.01).Logistic regression analysis showed that when the TyG index was a con-tinuous variable,it was significantly correlated with the risk of hypertension(OR=1.999,95％CI:1.393-2.869,P=0.001).When the index was used as a categorical variable,with Q1as a ref-erence,TyG index in Q3 and Q4 was associated with an increase in OR of hypertension(OR=1.869,95％CI:1.220-2.865,P=0.004;OR=1.844,95％CI:1.125-3.020,P=0.015).After ad-justing cofounders,the association of TyG index and risk of hypertension was stronger in the fe-males(OR=2.618,95％CI:1.312-5.221,P=0.006)than the males(OR=1.783,95％CI:1.151-2.761,P=0.010),and in the patients ≥65 years old(OR=3.277,95％CI:1.600-6.741,P=0.001)than those＜65 years old(OR=1.782,95％CI:1.076-2.949,P=0.025).Conclusion TyG index is closely associated with hypertension in patients with cerebral hemorrhage,especially in women and elderly.

AIM To study the chemical constituents from the branches and leaves of Michelia yunnanensis Franch.ex Finet & Gagnep.and their anti-inflammatory activities.METHODS The methanol extract was isolated and purified by silica gel,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Twenty compounds were isolated and identified as dihydrodehydrodiconifenyl alcohol(1),8-hydroxypinoresinol(2),lariciresinol(3),isolariciresinol(4),(7S,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-aldehyde(5),thero-2,3-bis-(4-hydroxy-3-methoxypheyl)-3-methoxy-propanol(6),evofolin B(7),(E)-p-coumaryl alcohol γ-O-methyl ether(8),ω-hydroxypropioguaiacone(9),sinapaldehyde(10),isoscopoletin(11),6-hydroxy-5,7-dimethoxycoumarin(12),2α,3α-dihydroxy-2-methylbutyrolactone(13),6-hydroxy-3(1-hydroxy-1-methylethyl)-6-methyl-2-cyclohexen-1-one(14),benzofuran-2-carboxaldehyde(15),3,4-dihydroxy-5-methoxybenzaldehyde(16),3,5-dimethoxy-4-hydroxybenzaldehyde(17),3,4-dihydroxybenzaldehyde(18),3,4-dihydroxybenzoic methyl ester(19),vanillic acid(20).The inhibition rate of compound 1 on NO was 45.39％±0.32％.CONCLUSION Compounds 1-16,18-20 are first isolated from this plant.Compound 1 has anti-inflammatory activity.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.