ObjectiveThe study aims to investigate the intervention effect of modified Xiangsha Liujunzitang （M-XSLJZ） on intestinal-derived lipopolysaccharide （LPS）-activated Kupffer cell inflammation in rats with hyperlipidemia spleen deficiency syndrome. MethodsSeventy male SD rats were randomly divided into seven groups （n=10）： blank control （CON）， high-fat diet without spleen deficiency （HFD）， high-fat diet with spleen deficiency （SD-HFD）， M-XSLJZ low-， medium-， and high-dose groups （XS-L， XS-M， XS-H）， and western medicine control （R）. Spleen deficiency was induced in SD-HFD， XS-L， XS-M， XS-H， and R groups via irregular diet combined with exhaustive swimming for 15 days. The CON group received a standard diet， while other groups were fed a high-fat diet for 10 weeks to establish the hyperlipidemia model. After successful modeling， rats were treated for 8 weeks： M-XSLJZ was administered at 3.51， 7.02， 14.04 g·kg^-1 in XS-L， XS-M， and XS-H groups， respectively. The R group received 9×10^-4 g·kg^-1 of a reference drug. D-xylose excretion rate was measured by the phloroglucinol method. Blood lipids were assessed using an automated biochemical analyzer. Hematoxylin-eosin （HE） staining was used to evaluate the pathological conditions of the liver， and oil red O staining was used to observe the lipid deposition in the liver. The levels of LPS， portal vein serum LPS， LPS-binding protein （LBP）， serum interleukin-6 （IL-6）， IL-1β， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence was used to evaluate CD86 expression and CD68/TLR4 co-localization in the liver. Protein levels of TLR4， MyD88， NF-κB p65， and p-NF-κB p65 in Kupffer cells were analyzed via Western blot automated protein analysis. Hepatic IL-6， TNF-α， and IL-1β mRNA and protein levels were measured using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the CON group， the SD-HFD group showed a decrease in D-xylose excretion （P<0.01）. TC， TG， HDL-C， and LDL-C increased （P<0.05， P<0.01）. A large number of hepatic lipid vacuoles and orange-red lipid droplet deposition appeared in the liver. Ileal LPS， portal LPS， and LBP increased （P<0.05， P<0.01）. The levels of serum IL-6， TNF-α， and IL-1β increased （P<0.01）. The expression of CD86 was upregulated （P<0.01）， and the co-expression of CD68 and TLR4 was enhanced. The protein levels of TLR4， MyD88， and p-p65 in Kupffer cells increased （P<0.01）. The mRNA and protein levels of IL-6， TNF-α， and IL-1β increased （P<0.05， P<0.01）. Compared with the HFD group， the SD-HFD group exhibited decreased D-xylose excretion （P<0.01）， higher HDL-C， LDL-C （P<0.05）， increased portal LBP and LPS （P<0.05）， increased serum IL-6 and TNF-α （P<0.01）， upregulated CD86 （P<0.01）， enhanced CD68/TLR4 co-expression， and higher TNF-α mRNA/protein （P<0.05）. Compared with the SD-HFD group， all M-XSLJZ treatment groups showed reduced TC， TG， and LDL-C （P<0.05， P<0.01）. XS-H and R groups displayed improved hepatic lipid deposition. XS-H and R groups had lower ileal LPS， portal LPS， and LBP levels （P<0.05， P<0.01）. All M-XSLJZ treatment groups exhibited reduced serum IL-6， IL-1β， and TNF-α （P<0.01）. The XS-H group showed downregulated CD86 （P<0.01） and weakened CD68/TLR4 co-expression. The XS-H group had reduced TLR4， MyD88， and p-NF-κB p65 in Kupffer cells （P<0.01）. XS-H and R groups showed lower IL-6， TNF-α， and IL-1β mRNA/protein （P<0.05， P<0.01）. ConclusionM-XSLJZ may exert its lipid-lowering effects by inhibiting intestinal-derived LPS and alleviating Kupffer cell inflammation in the liver.

Objective:Integrating genes and GEO database related cuproptosis chips,to analyze connection between cupropto-sis genes,immune infiltration and myocardial infarction(MI),construct risk prediction model,predict Western medicine and Chi-nese medicine,analyze miRNA-mRNA regulatory network,and to provides a new research direction for the future study of MI-related cuproptosis mechanism and immune infiltration.Methods:By GEO database retrieval of MI related chips,standardized processing and MI-related cuproptosis genes screening were performed,and immunoinfiltration analysis and quantification were performed based on the treated gene expression matrix,correlation between immune infiltrating cells and function was analyzed,as well as their differ-ences in MI group and the control group.Cuproptosis genes that most related to MI in immune infiltration were screened out,and the risk model was constructed to analyze the risk probability of cuproptosis genes in MI.The Enrichr website and Coremine Medical data-base were used to predict cuproptosis-related genes in MI in Western medicine and traditional Chinese medicine.Finally,the up-stream mirnas of FDX1 and SLC31A1 were predicted by miRTarBase,Starbase and Targetscan databases,and miRNA-mRNA regula-tory networks were constructed.Results:Correlation of immune infiltration showed that Tfh cells and B cells had the strongest positive correlation(r=0.68),while regulatory T cells and iDC had the strongest negative correlation(r=-0.63);the difference analysis of im-mune infiltration showed that the differences among mast cells,NK cells and Th1 cells in the MI group at the cellular level were the most significant(P<0.001);and the differences in APC co-inhibition and MHCⅠ at the functional level were the most significant(P<0.001).Six genes with the highest correlation between immune cells and immune function were screened out:ATP7A,DLD,FDX1,LIAS,LIPT1 and SLC31A1.Results of the risk model showed that the high levels of FDX1 and SLC31A1 were negatively correlated with the risk prediction of MI.A total of 21 Western medicines and 30 traditional medicines were predicted by database comparison.miRTarBase,Starbase and Targetscan databases predicted 9 upstream miRNAs of cuproptosis-related genes in MI,including has-miR-122-5p.Conclusion:Tfh cells,B cells,para-inflammatory,typeⅠinterferon response and other related immune cells and functions may play important roles in pathogenesis and prognosis of MI.FDX1 and SLC31A1 as the key genes of cuproptosis process,are negatively correlated with MI.A total of 30 kinds of traditional Chinese medicines including Spirulina,sheep liver,Wen ezhu,Pian jianghuang and Yujin may have potential value in treatment of MI.Finally,9 miRNAs including has-miR-122-5p may play an important role in the regulation of cuproptosis in myocardial infarction.

Diabetes mellitus(DM)is an endocrine metabolic disease mainly characterized by chronic hyperglycemia,which seriously threatens the health and quality of life of human beings,and with the improvement of living standard and unhealthy lifestyle in China,the incidence of DM continues to rise and tends to be younger,so it is urgent to carry out in-depth research on hypoglycemic treatment.DM is pathologically based on absolute or relative insulin deficiency,and there is no radical cure for it,and Western medicine mostly adopts insulin injection or oral hypoglycemic drugs for symptomatic treatment,which is effective but prone to toxic side effects in long-term use.Chinese medicine has the advantages of multi-path and multi-target in treating DM,and plays a role in lowering blood sugar by promoting insulin secretion,improving insulin resistance,regulating glucolipid metabolism and anti-oxidative stress,etc.Its efficacy is remarkable and the rate of toxic side effects is low.In recent years,there have been more studies on the mechanism of action of traditional Chinese medicine and compound prescriptions on animal models of DM.By reviewing the relevant literature in recent years,the author has systematically sorted out the mechanism of hypoglycemic action of single Chinese medicine,traditional Chinese medicine compound prescriptions,effective components of traditional Chinese medicine and their related experimental designs,from promoting insulin secretion,inhibiting gluconeogenesis,promoting glycogen synthesis,improving insulin resistance,inhibiting glycosidase activity,alleviating oxidative stress damage,inhibiting inflammatory response and regulating intestinal stress.The study and experimental design of the hypoglycemic mechanism of Chinese medicine were summarized in terms of promoting insulin secretion,inhibiting gluconeogenesis,promoting glycogen synthesis,improving insulin resistance,inhibiting glucosidase activity,alleviating oxidative stress damage,inhibiting inflammatory response and regulating intestinal flora,etc.,with a view to providing reference for the wider clinical application of Chinese medicine in hypoglycemia and its in-depth pharmacodynamic study.

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Objective:To explore a solution for the construction of the CCI index with an example of cerebral infarction to provide a guide for adjusting the policy of Diagnosis-Intervention Packet.Methods:Lasso regression was used to screen for comorbidities to construct the model,K-means clustering was used for case severity categorization.CCI indices were calculated as one plus the sum of standardized regression coefficients.Results:According to the analysis,five key variables were found,including other disorders of the lungs,non-insulin-dependent diabetes mellitus with ketoacidosis,systemic inflammatory response syndrome of non-infectious etiology with organ failure,acute duodenal ulcer with bleeding,and chronic obstructive pulmonary disease with acute lower respiratory tract in-fection,with CCI indices of 1,1,1.026,1.034,and 1.101.Simulated calculation's result showed a decrease in medical insurance pay-ment losses after applying CCI indices.Conclusion:The CCI index construction scheme based on Lasso regression and K-means clus-tering is reasonable and effective.

Objective To observe the effects of Jianpi Qutan Huayu Prescription on oxidative stress and inflammatory response in mini-pigs with atherosclerosis(AS);To explore its mechanism based on the NOX5-ERK1/2 signaling pathway.Methods Twelve Bama mini-pigs were randomly divided into control group,model group,and Jianpi Qutan Huayu Prescription low-and high-dosage groups,with 3 pigs in each group.A high-fat diet was used to feed for 24 weeks to construct an AS model,and the treatment group was also supplemented with Jianpi Qutan Huayu Prescription in the feed.The general condition of mini-pigs(body length,abdominal circumference,body mass,food intake,and fecal water content)was measured at week 0,16,and 24 of administration,HE staining was used to observe the morphology of aortic tissue,while oil red O staining was used to observe lipid deposition in aortic and myocardial tissue,transmission electron microscopy was used to observe the ultrastructure of aortic tissue,and a fully automated biochemical analyzer was used to detect serum contents of TC,HDL-C,and LDL-C.ELISA was used to detect the contents of serum reactive oxygen species(ROS),interleukin(IL)-6,IL-10,tumor necrosis factor(TNF)-α,hypersensitivity-C-reactive protein(hs-CRP),vascular cell adhesion molecule-1(VCAM-1),and intercellular adhesion molecule-1(ICAM-1).Western blot was used to detect the expressions of NADPH oxidase 5(NOX5),extracellular signal regulated kinase 1/2(ERK1/2),p-ERK1/2,VCAM-1,and proliferating cell nuclear antigen(PCNA)proteins.Results Compared with the control group,the abdominal circumference,body mass,and food intake of mini-pigs in the model group increased at 16 and 24 weeks(P<0.01),there was significant thickening of the inner membrane of aorta,destruction of endothelial cells,lipid deposition,edema of smooth muscle cells,and significant swelling of mitochondria,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,VCAM-1,and ICAM-1 increased,while the content of HDL-C decreased(P<0.01);the expressions of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue increased(P<0.01).Compared with the model group,Jianpi Qutan Huayu Prescription low-and high-dosage groups showed a decrease in abdominal circumference,body mass,and food intake at 16 and 24 weeks(P<0.05,P<0.01),the plaque area and lipid deposition were reduced,and the damage to endothelial cells was alleviated,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,ICAM-1,and VCAM-1 decreased,and the content of HDL-C increased(P<0.01,P<0.05);the expressiond of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue decreased(P<0.01,P<0.05).Conclusion Jianpi Qutan Huayu Prescription can effectively alleviate AS in mini-pigs,and its mechanism may be related to inhibiting the activation of the NOX5-ERK1/2 signaling pathway and alleviating oxidative stress-induced inflammatory response.

ObjectiveTo analyse the clinical characteristics of different traditional Chinese medicine （TCM） syndromes in patients with heart failure based on information from electronic medical record. MethodsA cross-sectional study was conducted to collect clinical data of all inpatients with heart failure in the Department of Cardiology， Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 1， 2019 to December 31， 2020. A database of clinical TCM data was established to explore the characteristics of clinical data of basic information， syndromes and syndrome element types， and biochemical indexes. The distribution of TCM syndromes and syndrome elements in heart failure patients were also analysed， and the basic information and biochemical indexes of the patients with top 7 different TCM syndrome types were compared. ResultsA total of 1676 inpatients with heart fai-lure were included. The top 7 TCM syndromes of heart failure were syndrome of phlegm turbidity and blood stasis （477 cases， 28.46%）， syndrome of qi deficiency and blood stasis （439 cases， 26.19%）， syndrome of qi deficiency and blood stasis with water retention （274 cases， 16.35%）， syndrome of yang deficiency with water retention （145 cases， 8.65%）， syndrome of qi and yin deficiency （104 cases， 6.21%）， syndrome of qi and yin deficiency with blood stasis （80 cases， 4.77%）， syndrome of heart yang deficiency （59 cases， 3.52%）. Among the 1676 patients， 6 syndrome elements accounted for more than 5%. Blood stasis accounted for the highest proportion of TCM syndrome element type （1292 cases， 77.09%）， followed by qi deficiency （919 cases， 54.83%）， phlegm （498 cases， 29.71%）， water retention （434 cases， 25.89%）， yang deficiency （215 cases， 12.82%） and yin deficiency （191 cases， 11.40%）. Among the 1676 patients， 1308 cases of acute heart failure mainly showed syndrome of phlegm turbidity and blood stasis （386 cases， 29.51%）， and 368 of chronic heart fai-lure mainly showed syndrome of qi deficiency and blood stasis （118 cases， 32.07%）. Patients with syndrome of phlegm turbidity and blood stasis had the shortest disease duration of 0.3 months， while those with syndrome of heart yang deficiency had the longest disease duration of 15 months. The proportion of syndrome of phlegm turbidity and blood stasis was the highest in patients with heart failure combined with coronary artery disease， the proportion of syndrome of qi deficiency and blood stasis with water retention was the highest in patients with heart failure combined with atrial fibrillation， and the proportion of patients with syndrome of qi deficiency and blood stasis with water retention and syndrome of yang deficiency with water retention in those applying diuretics during the hospital stay was the highest with more than 86%. The different 7 TCM syndromes showed statistically difference in patients with complications including coronary artery disease， old myocardial infarction， atrial fibrillation， pre and post-admission medication usage including intravenous vasodilators， cardiac stimulants， diuretics， and level of blood chloride， blood urea， blood creatinine， blood bicarbonate， blood albumin， and blood total bilirubin （P＜0.05）. ConclusionThe most common TCM syndromes in patients with heart failure are syndrome of phlegm turbidity and blood stasis and syndrome of qi deficiency and blood stasis. Different TCM syndromes have different characteristics in gender， disease complications， medication before and after admission， and blood indexes.

ObjectiveTo explore the mechanism of Shenqi Gualou Xiebai Banxia Decoction （参芪瓜蒌薤白半夏汤， SGXBD） in the treatment of atherosclerosis. MethodsThirty Apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into five groups： model group， rosuvastatin group， low-， moderate-， and high-dose SGXBD， with six mice in each group. They were fed a high-fat diet to prepare for atherosclerosis model. Another six C57BL/6J wild-type mice were set as the blank group. After modeling， the low-， moderate-， and high-dose SGXBD groups were gavaged with 6.46， 12.92， and 25.84 g/（kg·d） of SGXBD， respectively. The rosuvastatin group was given 1.55 mg/（kg·d） of rosuvastatin tablets by gavage. The blank group and model group were given 0.5 ml saline by gavage. After four weeks， the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in the serum of each group were detected， as well as TC and TG in the liver. The serum bile acid level was detected by enzyme cycling colorimetry. The mRNA and protein expression of peroxisome proliferator-activated receptor γ （PPARγ）， sterol regulatory element-binding protein 2 （SREBP2）， 3-hydroxy-3-methylglutaryl-CoA reductase （HMGCR）， and cholesterol 7α-hydroxylase （CYP7A1） in the liver were detected by real-time RT-PCR and Western blot. ResultsCompared with the blank group， the model group showed significant increases in serum TG， TC， and LDL-C levels， and significant decreases in HDL-C and bile acid levels； the levels of TG and TC in the liver， as well as the expression of SREBP2 and HMGCR proteins and mRNA in the liver significantly increased， while the expression of PPARγ and CYP7A1 proteins and mRNA significantly decreased （all P＜0.01）. Compared with the model group， the rosuvastatin group and high-dose SGXBD group showed significant decreases in serum TG， TC， and LDL-C levels and liver TG and TC levels， and significant increases in bile acid levels； the expression of PPARγ and CYP7A1 proteins and mRNA increased， while the expression of SREBP2 and HMGCR proteins and mRNA decreased； the low-dose SGXBD group showed significant decreases in serum TC and LDL-C levels and liver TC level （P＜0.05 or P＜0.01）. Compared with the rosuvastatin group， the low-dose SGXBD group had a significantly higher liver TC level， while the high-dose SGXBD group had a significantly lower liver TC level， CYP7A1 mRNA level， and PPARγ protein expression level， and a significantly higher SREBP2 protein expression level （P＜0.05 or P＜0.01）. Compared with the low- and moderate-dose groups， the high-dose SGXBD group had significantly lower serum TG and liver TC levels （P＜0.05）. ConclusionSGXBD may improve blood lipid levels and exhibit anti-atherosclerotic effects by regulating the protein level of PPARγ and simultaneously affecting the synthesis of liver cholesterol and the conversion of cholesterol to bile acids.

Objective:To establish a method for the determination of 4-methyl-2-pentanol in the air of workplace by gas chromatography.Methods:In January 2022, 4-methyl-2-pentanol in the air of workplace was collected by activated carbontube, eluted with dichloromethane-methanol (95∶5, V/ V), separated by capillary column and determined by gas chromatogram. Results:The limit of detection for 4-methyl-2-pentanol was 0.04 μg/ml. The linear range of 4-methyl-2-pentanol was 0.16-1616.60 μg/ml, with the regression equation of y=1.94 x-5.48, and the coefficient correlation was 0.99958, and the minimum detection concentration was 0.03 mg/m 3 (collected sample volume was 1.50 L). The within-run precisions were 1.08%-1.75% and the between-run precisions were 1.41%-2.52%. The desorption rates were 95.15%-99.91%. The samples could be stored at least 3 days at room temperature and 7 days at 4 ℃ without significant loss. Conclusion:The method has the advantages of good precision, high sensitivity and simple operation. It is suitable for the determination of 4-methyl-2-pentanol in the air of workplace.

Objective:To establish a method for the determination of 4-methyl-2-pentanol in the air of workplace by gas chromatography.Methods:In January 2022, 4-methyl-2-pentanol in the air of workplace was collected by activated carbontube, eluted with dichloromethane-methanol (95∶5, V/ V), separated by capillary column and determined by gas chromatogram. Results:The limit of detection for 4-methyl-2-pentanol was 0.04 μg/ml. The linear range of 4-methyl-2-pentanol was 0.16-1616.60 μg/ml, with the regression equation of y=1.94 x-5.48, and the coefficient correlation was 0.99958, and the minimum detection concentration was 0.03 mg/m 3 (collected sample volume was 1.50 L). The within-run precisions were 1.08%-1.75% and the between-run precisions were 1.41%-2.52%. The desorption rates were 95.15%-99.91%. The samples could be stored at least 3 days at room temperature and 7 days at 4 ℃ without significant loss. Conclusion:The method has the advantages of good precision, high sensitivity and simple operation. It is suitable for the determination of 4-methyl-2-pentanol in the air of workplace.