ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula （养心通脉方， YTF） in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group （n=12） and a modeling group （n=60）. The modeling group was subjected to a high-fat diet， intragastric administration of vitamin D3， and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group， YTF low-， medium-， and high-dose groups， and the atorvastatin calcium group， with 8 rats in each group and 1 rat reserved. The YTF low-， medium-， and high-dose groups received YTF at 6， 12， and 18 g/（kg·d） by gavage， respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/（kg·d） by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/（kg·d） by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）， myocardial enzymes including cardiac troponin T （cTnT）， creatine kinase MB （CK-MB）， and lactate dehydrogenase （LDH）， and inflammatory factors including interleukin-1β （IL-1β） and interleukin-10 （IL-10） were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group， model group， and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group， the model group showed increased levels of TC， TG， LDL-C， cTnT， CK-MB， LDH， and IL-1β， along with decreased levels of HDL-C and IL-10 （P＜0.05 or P＜0.01）. Compared to the model group， all treatment groups exhibited decreased levels of TC， LDL-C， CK-MB， and LDH， along with increased IL-10 levels. Among these， the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups （P＜0.05 or P＜0.01）. HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling， disordered arrangement， pyknosis， and disappearance of nuclei， thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group， model group， and YTF high-dose group， including 109 hypermethylated and 131 hypomethylated genes； eif2ak3 was identified as a key differentially methylated gene. Compared to the control group， the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 （eIf2ak3）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， and Bax， along with a decreased level of B-cell lymphoma-2 （Bcl-2） protein （P＜0.05 or P＜0.01）. Compared to the model group， the YTF high-dose group showed decreased protein levels of eIf2ak3， p-PERK， ATF4， CHOP， and Bax， and an increased level of Bcl-2 protein （P＜0.05 or P＜0.01）. ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway， thereby inhibiting endoplasmic reticulum stress， reducing myocardial cell apoptosis， and exerting therapeutic effects in coronary heart disease blood stasis syndrome.

Objective To investigate the effects and mechanism of Xuefu Zhuyu Decoction in oxidative stress in coronary heart disease model rats with heart blood stasis syndrome based on Keap1/Nrf2 signaling pathway.Methods The rats were divided into normal group,sham-operation group,model group,Xuefu Zhuyu Decoction group and trimetazidine group.The rat model of coronary heart disease with heart blood stasis syndrome was established by ligation of the left anterior descending branch of the coronary artery.Xuefu Zhuyu Decoction group and trimetazidine group were administrated with the corresponding drugs at the dosages of 14.04 g/kg and 5.4 mg/kg,respectively,and normal group,sham-operation group and model group were administrated with the same volume of normal saline for 14 days.The general state of rats was observed,body mass was recorded and electrocardiogram was collected.Echocardiography was used to examine cardiac functions(LVEF,LVFS,LVIDd,LVIDs);the morphology of myocardial tissue was observed by HE staining,serum malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)were detected by ELISA,the positive expressions of Keap1,Nrf2,HO-1 and NQO1 in myocardial tissue were detected by immunohistochemistry.Results Compared with the normal group and sham-operation group,the rats in the model group showed signs of mental fatigue,reduced activity,dull fur,purple claws,and a significant decrease in body mass(P<0.01);the ST segment in lead Ⅱ of the electrocardiogram was significantly elevated,LVEF and LVFS were significantly reduced,and LVIDd and LVIDs significantly increased(P<0.01),with severe degeneration and necrosis of myocardial cells,disappearance of striated structures,disordered arrangement of myocardial fibers,infiltration of inflammatory cells;the serum MDA content significantly increased,while the activities of SOD,GSH-Px and T-AOC significantly decreased(P<0.01);the positive expressions of Keap1 and Nrf2 in myocardial tissue significantly increased,while the positive expression of HO-1 and NQO1 significantly decreased(P<0.01).Compared with the model group,the rats in Xuefu Zhuyu Decoction group and trimetazidine group showed improvement in their mental state,increased activity,shiny fur,rosy nails,and significantly increased body mass(P<0.01);the ST segment of the electrocardiogram decreased to varying degrees,with significant increases in LVEF and LVFS,and significant decreases in LVIDd and LVIDs(P<0.01);a large number of myocardial cells survived,the arrangement of myocardial fibers was relatively regular,and the infiltration of inflammatory cells was significantly reduced;the serum MDA content was significantly reduced,while the activities of SOD,GSH-Px and T-AOC significantly increased(P<0.01);the positive expression of Keap1 in myocardial tissue significantly decreased,while the positive expressions of Nrf2,HO-1 and NQO1 significantly increased(P<0.01).Conclusion Xuefu Zhuyu Decoction may inhibit oxidative stress by activating Keap1/Nrf2 signaling pathway to improve the pathological morphology and structural damage of myocardial tissue and promote the recovery of cardiac functions in rats with heart blood stasis syndrome of coronary heart disease.

Objective To investigate the effects and mechanism of Xuefu Zhuyu Decoction in oxidative stress in coronary heart disease model rats with heart blood stasis syndrome based on Keap1/Nrf2 signaling pathway.Methods The rats were divided into normal group,sham-operation group,model group,Xuefu Zhuyu Decoction group and trimetazidine group.The rat model of coronary heart disease with heart blood stasis syndrome was established by ligation of the left anterior descending branch of the coronary artery.Xuefu Zhuyu Decoction group and trimetazidine group were administrated with the corresponding drugs at the dosages of 14.04 g/kg and 5.4 mg/kg,respectively,and normal group,sham-operation group and model group were administrated with the same volume of normal saline for 14 days.The general state of rats was observed,body mass was recorded and electrocardiogram was collected.Echocardiography was used to examine cardiac functions(LVEF,LVFS,LVIDd,LVIDs);the morphology of myocardial tissue was observed by HE staining,serum malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)were detected by ELISA,the positive expressions of Keap1,Nrf2,HO-1 and NQO1 in myocardial tissue were detected by immunohistochemistry.Results Compared with the normal group and sham-operation group,the rats in the model group showed signs of mental fatigue,reduced activity,dull fur,purple claws,and a significant decrease in body mass(P<0.01);the ST segment in lead Ⅱ of the electrocardiogram was significantly elevated,LVEF and LVFS were significantly reduced,and LVIDd and LVIDs significantly increased(P<0.01),with severe degeneration and necrosis of myocardial cells,disappearance of striated structures,disordered arrangement of myocardial fibers,infiltration of inflammatory cells;the serum MDA content significantly increased,while the activities of SOD,GSH-Px and T-AOC significantly decreased(P<0.01);the positive expressions of Keap1 and Nrf2 in myocardial tissue significantly increased,while the positive expression of HO-1 and NQO1 significantly decreased(P<0.01).Compared with the model group,the rats in Xuefu Zhuyu Decoction group and trimetazidine group showed improvement in their mental state,increased activity,shiny fur,rosy nails,and significantly increased body mass(P<0.01);the ST segment of the electrocardiogram decreased to varying degrees,with significant increases in LVEF and LVFS,and significant decreases in LVIDd and LVIDs(P<0.01);a large number of myocardial cells survived,the arrangement of myocardial fibers was relatively regular,and the infiltration of inflammatory cells was significantly reduced;the serum MDA content was significantly reduced,while the activities of SOD,GSH-Px and T-AOC significantly increased(P<0.01);the positive expression of Keap1 in myocardial tissue significantly decreased,while the positive expressions of Nrf2,HO-1 and NQO1 significantly increased(P<0.01).Conclusion Xuefu Zhuyu Decoction may inhibit oxidative stress by activating Keap1/Nrf2 signaling pathway to improve the pathological morphology and structural damage of myocardial tissue and promote the recovery of cardiac functions in rats with heart blood stasis syndrome of coronary heart disease.

Objective To investigate the biological basis of disease and syndrome by studying the spectrum of myocardial tissue metabolites in the rat model of coronary heart disease with heart blood stasis syndrome.Methods SD rats were randomly divided into sham-operation group and model group.The left anterior descending coronary artery was ligated to prepare the rat model of coronary heart disease with heart blood stasis syndrome.The general condition was observed,and the tongue chromaticity,electrocardiogram,cardiac function were detected.HE staining and transmission electron microscopy were used to observe myocardial tissue morphology and ultrastructure.UPLC-MS technology was used to investigate the differential metabolites in rat myocardial tissue,and enrichment analysis was conducted on metabolic pathways.Results Compared with the sham-operation group,the tongue chromaticity R,G,B values of model group rats were significantly reduced(P<0.05),ECG heart rate and ST segment elevation amplitude significantly increased(P<0.05),LVEF and LVFS significantly decreased,and LVIDs and LVIDd significantly increased(P<0.05).Myocardial tissue pathology revealed that the structure was blurred,inflammatory cells infiltrated,mitochondria swelled,ruptured,and dissolved,and crista structure fracture decreased.A total of 29 potential biomarkers with significant differences between the sham-operation group and the model group were identified in metabolomics(7 upregulated and 22 downregulated),with the majority of 10 pathways enriched in thiamine metabolism,arginine biosynthesis,purine metabolism,aminoacyl-tRNA biosynthesis,alanine,aspartate and glutamate metabolism,pentose and glucuronate interconversions,glycolysis/gluconeogenesis,valine,leucine and isoleucine degradation,TCA cycle,pyruvate metabolism.Conclusion Ligation of the left anterior descending coronary artery can mimic the pathological process of coronary heart disease with blood stasis syndrome in a good way,and its pathological mechanism involves the disruption of multi-level metabolic networks such as glucose metabolism,mitochondrial energy metabolism,amino acid metabolism,protein biosynthesis,and purine metabolism.

In the case of cardiac dysfunction， energy metabolism changes and the metabolism of myocardial substrates is reconstructed， as manifested by variation in the selection and utilization of energy substrates such as fatty acids and glucose. Persistent metabolic disorders of substrates will decrease energy supply， thus resulting in the occurrence and development of heart failure. Metabolic remodeling of substrate is resulted from the decline of visceral function and the accumulation of pathological products. Deficient Qi stagnation is the core pathogenesis. Deficient Qi （heart Qi deficiency， insufficient energy） is the root cause， which exists in the whole disease course. Stagnation （phlegm， blood stasis， fluid， lipid toxic products， lactic acid， etc.） is the symptom， which evidences the aggravation of the disease. Deficient Qi and stagnation are intertwined and causal， which form a spiral vicious circle. The typical syndrome is excess resulted from deficiency and deficiency-excess in complexity. The treatment principle is reinforcing healthy Qi and tonifying deficiency， dredging and removing pathogen. At the early stage， the method of reinforcing healthy Qi and tonifying deficiency （benefiting Qi） should be used， and the method of dredging and removing pathogen （activating blood） can be applied according to the conditions of patients. At the middle and late stages， both reinforcing healthy Qi and tonifying deficiency （benefiting Qi and warming Yang） and dredging and removing pathogen （activating blood， resolving stasis， and excreting water） should be emphasized. Chinese medicine can be applied according to the pathogenesis， thereby promoting the utilization of fatty acids， glucose， and other substrates and reducing the accumulation of toxic products derived from metabolic remodeling of substrate. Thus， both the root cause and symptoms can be alleviated， further improving cardiac energy metabolism and heart function.

Objective To investigate CT and MRI features of abdominal huge liposarcoma,and improve the preoperative diagnostic accuracy. Methods The CT and MRI findings of 1 7 cases with abdominal huge liposarcoma proved by operation and pathology were analyzed and correlated with pathologic subtypes retrospectively.Results In 17 cases,16 cases were located in retroperitoneal,1 case was located in the abdominal cavity.The average maximal diameter of the lesions was 17 cm.In all cases,main components of well differentiated liposarcomata (n=7) were fat density on CT and MRI,and enhanced slightly,3 cases were multiple lesions,1 case of sclerosing liposarcoma contained massive patchy calcification,1 case was fatless.Myxoid liposarcoma (n=5)were similar to cystic on CT and MRI features,enhanced with latticed or cloudy components slightly to moderately .Dedifferentiated liposarcoma (n=2)has both fat and soft tissue inside and the dividing line was clear.The soft tissue mass unevenly obviously enhanced.Mixed liposarcoma (n=3)had the imaging characteristics above different types,2 cases contained no fat composition.Conclusion Liposarcoma pathological subtype has diversity,and various subtypes have certain characteristic on CT and MRI imaging features.

Objective To elucidate the malnutrition in patients with hospital-acquired acute kidney injury(AKI), and to examine the association betweensubjective global assessment (SGA) and prognosis.Methods Adult patients with hospital-acquired AKI were prospectively enrolled in this cohort study.Nutritional evaluations, including SGA, anthropometric and serum nutritional markers were conducted at enrollment.Overall survival at 90 days among different SGA scores was analyzed using Kaplan-Meier methods, and differences were tested using the log-rank test.The Cox model was used to analyze the relationship between SGA scores and all-cause mortality after adjusting for confounders.Results A total of 170 patients were enrolled.The prevalence of moderate malnutrition(SGA B) and severe malnutrition(SGA C) was 51.8％ and 22.9％ respectively, while patients with normal nutrition(SGA A) accounted for 25.3％.After 90 days follow-up, all-cause mortality was 9.8％ in SGA A group, 34.9％ in SGA B group and 56.8％inSGACgrouprespectively. Afteradjustingforage,sex,dialysis,ventilation, hemoglobin, platelets and bilirubin, the hazard ratio(HR) of 90 days all-cause mortality was 4.0(95％ CI 1.42-11.22, P=0.008) in malnutrition group (SGA B group and SGA C group) compared with SGA A group.The Kaplan-Meier curve also revealed that the worse the SGA score was, the lower the cumulative survival became (P＜0.01).Conclusion SGA score is an independent risk factor for all-cause mortality within 90 days in patients with hospital-acquired acute kidney injury.