ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

Objective Based on apolipoprotein a-Ⅰ(Apoa-Ⅰ)gene knockout mice,the role and mechanism of phosphotidylcholine(PC)in improving cholesterol reverse transport were explored.Methods Thirty Apoa-Ⅰ-/-mice were randomly divided into an Apoa-Ⅰ-/-group,Apoa-Ⅰ-/-+HFD group,and Apoa-Ⅰ-/-+HFD+PC group using the random number table method;30 C57BL/6J mice were randomly divided into a WT group,WT+HFD group,and WT+HFD+PC control groups,with 10 mice in each group.The Apoa-Ⅰ-/-group and WT groups were fed basic feed,while the other groups were fed high-fat feed for 8 weeks to establish a hyperlipidemia model.From the 9th week,the WT+HFD+PC group and Apoa-Ⅰ-/-+HFD+PC group were given PC 2.5 g/(kg·d),while the remaining mice were given physiological saline by gavage for a total of 4 weeks of intervention.The serum lipid levels of the mice were detected using a fully automated analyzer.Hematoxylin and eosin and Oil red O staining were used to observe pathological and morphological changes,and the COD-PAP method was used to detect cholesterol levels in mouse liver tissue.The ELISA method was used to detect LCTA levels in mouse serum,and RT-qPCR and Western Blot method were used to detect the mRNA and protein expression of cholesterol ATP binding cassette transporter A1(ABCA1),ATP binding cassette transporter G1(ABC A1),lecithin cholesterol acyltransferase(LCAT),hepatic lipase(HL),scavenger receptor class B type Ⅰ(SR-B1),and low-density lipoprotein receptor(LDL-R)in liver tissue.Results Compared with the WT group,the serum lipid levelsof WT+HFD group mice were significantly increased(P＜0.01),LCAT levels were significantly reduced(P＜0.05),hepatic fat vacuoles were obvious,hepatic lipid deposition was significant,and liver tissue TC levels were significantly increased(P＜0.01).The mRNA and protein expression of ABCA1,ABCG1,LCAT,SR-B1,HL,and LDL-R were significantly reduced(P＜0.05,P＜0.01).Compared with the WT+HFD group,serum lipid levels in the WT+HFD+PC group were significantly reduced(P＜0.05,P＜0.01),LCAT levels were significantly increased(P＜0.05),hepatic fat vacuoles were significantly reduced,hepatic lipid deposition was alleviated,and liver tissue TC levels were significantly reduced(P＜0.05);mRNA and protein expression of ABCA1,LCAT,SR-B1,HL and LDL-R were significantly increased(P＜0.05,P＜0.01).The serum levels of TC,TG,and LDL-C were significantly increased,while the levels of LCAT、HDL-C were significantly reduced(P＜0.05,P＜0.01)in the Apoa-Ⅰ-/-+HFD group mice.Hepatocytes underwent balloon-like transformation,liver lipid deposition was significantly aggravated,and liver tissue TC levels were significantly increased(P＜0.05).The mRNA and protein expression of ABCA1,LCAT and HL were significantly reduced(P＜0.05,P＜0.01).Compared with the WT+HFD+PC group mice,the Apoa-Ⅰ-/-+HFD+PC group mice showed a significant increase in serum lipid levels(P＜0.05,P＜0.01),LCAT levels were significantly reduced(P＜0.05),significant hepatic lipid vacuoles,significant hepatic lipid deposition,and a significant increase in TC levels in liver tissue(P＜0.05).Their mRNA and protein expression of ABCA1,ABCG1,LCAT,SR-B1,and HL were also significantly reduced(P＜0.05,P＜0.01).Conclusions Phosphatidylcholine can improve dyslipidemia by interfering with Apoa-Ⅰ and thus regulating cholesterol reverse transport.

AIM:This study aims to investigate the effects of baicalin on the hypoxia-inducible factor-1α(HIF-1α)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)axis and the ferroptosis induced by oxidized low-density lipoprotein(ox-LDL)in RAW264.7 macrophage-derived foam cells.METHODS:RAW264.7 cells were categorized into five groups:control,ox-LDL,baicalin+ox-LDL,ferrostatin-1(Fer-1;ferroptosis inhibitor)+ox-LDL,and baicalin+Fer-1+ox-LDL.To induce foam cell formation,RAW264.7 macrophages were exposed to 100 μg/mL ox-LDL for 24 h.Oil red O staining was employed to visualize lipid droplet formation in each group.The ultrastructure of the mitochondria was examined using transmission electron microscopy.Fluorescence microscopy was utilized to assess the fluorescence intensity of intracellular reactive oxygen species(ROS),lipid peroxides,and Fe2+.A colorimetric assay facilitated the measurement of malondialdehyde(MDA)and glutathione(GSH)levels.Additionally,Western blot analy-sis was conducted to quantify protein levels of HIF-1α,SLC7A11,and GPX4.RESULTS:The model group exhibited foam cell formation,abundant lipid droplets,significant swelling of mitochondrial structures,and observable shortening or disappearance of cristae.There was a marked increase in intracellular fluorescence intensity of ROS,lipid peroxides,and Fe2+,alongside elevated MDA levels and decreased GSH levels.HIF-1α protein expression was significantly increased,while SLC7A11 and GPX4 protein expressions were notably decreased(P<0.05).In comparison to the model group,both the baicalin+ox-LDL and Fer-1+ox-LDL groups demonstrated a significant reduction in lipid droplets,improved mitochon-drial structures,decreased fluorescence intensity of ROS,lipid peroxides,and Fe2+,as well as lower MDA levels and higher GSH levels.Additionally,HIF-1α expression significantly decreased,while SLC7A11 and GPX4 expressions sig-nificantly increased(P<0.05).Furthermore,the baicalin+Fer-1+ox-LDL group showed a more pronounced reduction in lipid droplets,near-normal mitochondrial structures,lower fluorescence intensity of ROS,lipid peroxides,and Fe2+,de-creased MDA levels,and increased GSH levels compared to the baicalin+ox-LDL group;HIF-1α,SLC7A11,and GPX4 protein expressions were also significantly reduced(P<0.05).CONCLUSION:Baicalin modulates the HIF-1α/SLC7A11/GPX4 axis,thereby inhibiting ox-LDL-induced ferroptosis in macrophage-derived foam cells.

Objective Based on apolipoprotein a-Ⅰ(Apoa-Ⅰ)gene knockout mice,the role and mechanism of phosphotidylcholine(PC)in improving cholesterol reverse transport were explored.Methods Thirty Apoa-Ⅰ-/-mice were randomly divided into an Apoa-Ⅰ-/-group,Apoa-Ⅰ-/-+HFD group,and Apoa-Ⅰ-/-+HFD+PC group using the random number table method;30 C57BL/6J mice were randomly divided into a WT group,WT+HFD group,and WT+HFD+PC control groups,with 10 mice in each group.The Apoa-Ⅰ-/-group and WT groups were fed basic feed,while the other groups were fed high-fat feed for 8 weeks to establish a hyperlipidemia model.From the 9th week,the WT+HFD+PC group and Apoa-Ⅰ-/-+HFD+PC group were given PC 2.5 g/(kg·d),while the remaining mice were given physiological saline by gavage for a total of 4 weeks of intervention.The serum lipid levels of the mice were detected using a fully automated analyzer.Hematoxylin and eosin and Oil red O staining were used to observe pathological and morphological changes,and the COD-PAP method was used to detect cholesterol levels in mouse liver tissue.The ELISA method was used to detect LCTA levels in mouse serum,and RT-qPCR and Western Blot method were used to detect the mRNA and protein expression of cholesterol ATP binding cassette transporter A1(ABCA1),ATP binding cassette transporter G1(ABC A1),lecithin cholesterol acyltransferase(LCAT),hepatic lipase(HL),scavenger receptor class B type Ⅰ(SR-B1),and low-density lipoprotein receptor(LDL-R)in liver tissue.Results Compared with the WT group,the serum lipid levelsof WT+HFD group mice were significantly increased(P＜0.01),LCAT levels were significantly reduced(P＜0.05),hepatic fat vacuoles were obvious,hepatic lipid deposition was significant,and liver tissue TC levels were significantly increased(P＜0.01).The mRNA and protein expression of ABCA1,ABCG1,LCAT,SR-B1,HL,and LDL-R were significantly reduced(P＜0.05,P＜0.01).Compared with the WT+HFD group,serum lipid levels in the WT+HFD+PC group were significantly reduced(P＜0.05,P＜0.01),LCAT levels were significantly increased(P＜0.05),hepatic fat vacuoles were significantly reduced,hepatic lipid deposition was alleviated,and liver tissue TC levels were significantly reduced(P＜0.05);mRNA and protein expression of ABCA1,LCAT,SR-B1,HL and LDL-R were significantly increased(P＜0.05,P＜0.01).The serum levels of TC,TG,and LDL-C were significantly increased,while the levels of LCAT、HDL-C were significantly reduced(P＜0.05,P＜0.01)in the Apoa-Ⅰ-/-+HFD group mice.Hepatocytes underwent balloon-like transformation,liver lipid deposition was significantly aggravated,and liver tissue TC levels were significantly increased(P＜0.05).The mRNA and protein expression of ABCA1,LCAT and HL were significantly reduced(P＜0.05,P＜0.01).Compared with the WT+HFD+PC group mice,the Apoa-Ⅰ-/-+HFD+PC group mice showed a significant increase in serum lipid levels(P＜0.05,P＜0.01),LCAT levels were significantly reduced(P＜0.05),significant hepatic lipid vacuoles,significant hepatic lipid deposition,and a significant increase in TC levels in liver tissue(P＜0.05).Their mRNA and protein expression of ABCA1,ABCG1,LCAT,SR-B1,and HL were also significantly reduced(P＜0.05,P＜0.01).Conclusions Phosphatidylcholine can improve dyslipidemia by interfering with Apoa-Ⅰ and thus regulating cholesterol reverse transport.

AIM:This study aims to investigate the effects of baicalin on the hypoxia-inducible factor-1α(HIF-1α)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)axis and the ferroptosis induced by oxidized low-density lipoprotein(ox-LDL)in RAW264.7 macrophage-derived foam cells.METHODS:RAW264.7 cells were categorized into five groups:control,ox-LDL,baicalin+ox-LDL,ferrostatin-1(Fer-1;ferroptosis inhibitor)+ox-LDL,and baicalin+Fer-1+ox-LDL.To induce foam cell formation,RAW264.7 macrophages were exposed to 100 μg/mL ox-LDL for 24 h.Oil red O staining was employed to visualize lipid droplet formation in each group.The ultrastructure of the mitochondria was examined using transmission electron microscopy.Fluorescence microscopy was utilized to assess the fluorescence intensity of intracellular reactive oxygen species(ROS),lipid peroxides,and Fe2+.A colorimetric assay facilitated the measurement of malondialdehyde(MDA)and glutathione(GSH)levels.Additionally,Western blot analy-sis was conducted to quantify protein levels of HIF-1α,SLC7A11,and GPX4.RESULTS:The model group exhibited foam cell formation,abundant lipid droplets,significant swelling of mitochondrial structures,and observable shortening or disappearance of cristae.There was a marked increase in intracellular fluorescence intensity of ROS,lipid peroxides,and Fe2+,alongside elevated MDA levels and decreased GSH levels.HIF-1α protein expression was significantly increased,while SLC7A11 and GPX4 protein expressions were notably decreased(P<0.05).In comparison to the model group,both the baicalin+ox-LDL and Fer-1+ox-LDL groups demonstrated a significant reduction in lipid droplets,improved mitochon-drial structures,decreased fluorescence intensity of ROS,lipid peroxides,and Fe2+,as well as lower MDA levels and higher GSH levels.Additionally,HIF-1α expression significantly decreased,while SLC7A11 and GPX4 expressions sig-nificantly increased(P<0.05).Furthermore,the baicalin+Fer-1+ox-LDL group showed a more pronounced reduction in lipid droplets,near-normal mitochondrial structures,lower fluorescence intensity of ROS,lipid peroxides,and Fe2+,de-creased MDA levels,and increased GSH levels compared to the baicalin+ox-LDL group;HIF-1α,SLC7A11,and GPX4 protein expressions were also significantly reduced(P<0.05).CONCLUSION:Baicalin modulates the HIF-1α/SLC7A11/GPX4 axis,thereby inhibiting ox-LDL-induced ferroptosis in macrophage-derived foam cells.

OBJECTIVES: To analyze sex and age distribution of global disease burden of calcific aortic valve disease (CAVD) from 1990 to 2021. METHODS: CAVD data during 1990-2021 were obtained from the IHME website for Global Burden of Disease (GBD). The prevalence, mortality, years lived with disability (YLDs), and disability-adjusted life years (DALYs) were analyzed by gender and age groups. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC). RESULTS: In 2021, there were 13.32 million CAVD patients and 142 000 deaths caused by CAVD globally. Age-standardized prevalence was higher in males (193.2/10⁵) than that in females (128.9/10⁵). Patients in 65-<85 age group accounted for 64.0% of total cases, while those ≥85 years old accounted for 16.1%. From 1990 to 2021, prevalence increased in both sexes with an AAPC of 0.72% for males and 0.57% for females, respectively. Prevalence grew fastest from 2000 to 2010, slowed thereafter, and declined from 2015 to 2021. In <65 years old, the mortality of males was 2.4 times higher than that of females, while in ≥85 years old, mortality of females (117.3/10⁵) exceeded that of males (99.1/10⁵). YLD rates increased with age, and were higher in males for all age groups. DALY rates decreased overall but increased in ≥85 years old, with a greater increase in females. CONCLUSIONS There are significant gender and age disparities in global disease burden of CAVD, with the elderly, especially super-elderly females deserving particular attention. It is recommended to develop personalized intervention strategies for these populations.
Humans ; Male ; Female ; Aged ; Calcinosis/mortality* ; Prevalence ; Global Burden of Disease ; Aged, 80 and over ; Middle Aged ; Aortic Valve/pathology* ; Aortic Valve Stenosis/epidemiology* ; Age Distribution ; Adult ; Disability-Adjusted Life Years ; Sex Distribution ; Global Health ; Aortic Valve Disease/epidemiology* ; Sex Factors

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective To explore the mechanism of modified Xiangsha Liujunzi Decoction in regulating apolipoproteinA-Ⅰ (apoA-Ⅰ),improving endoplasmic reticulum stress,regulating glucose and lipid metabolism,and preventing and treating dyslipidemia in mice. Methods Wild-type (WT) C57BL/6J mice were randomly divided into the WT,WT+high-fat diet(HFD),and WT+HFD+Xiangsha Liujunzi Decoction(XSLJZ) groups according to the random number table method. ApoA-Ⅰ-/-mice were randomly divided into the apoA-Ⅰ-/-,apoA-Ⅰ-/-+HFD,and apoA-Ⅰ-/-+HFD+XSLJZ groups (n=10) according to the random number table method. D12492 was used for HFD feeding to establish a hyperlipidemic mouse model. Modified XSLJZ (23.66g/kg) was administered daily by gavage from the ninth week. Serum and liver tissue were collected for testing after 4 weeks. An automatic biochemical analyzer was used to detect blood lipid levels;an enzyme-linked immunosorbent assay was used to detect serum fasting blood glucose (FBG) and insulin (INS) levels,and the INS resistance index (HOMA-IR) was calculated. Hematoxylin and eosin staining was used to observe the pathological changes in the liver. Oil red O staining was used to observe the lipid deposition in the liver. TG levels in liver tissue were detected using the microplate method. Real-time PCR was used to detect apoA-Ⅰ,glucose-regulated proteins (GRP78),sterol regulatory element binding protein-1c (SREBP-1c),acetyl CoA carboxylase 1 (ACC1),and fatty acid synthase (FASN) mRNA expression levels in liver tissue. The WES fully automated protein expression analysis system was used to detect apoA-Ⅰ,GRP78,inositol-requiring enzyme 1 (IRE1),p-IRE1,c-Jun N-terminal kinase (JNK),p-JNK,insulin receptor substrate (IRS1),p-IRS1,protein kinase B (Akt),p-Akt,SREBP-1c,ACC1,and FASN protein expression levels in liver tissue. Results Compared to the WT group,the WT+HFD group showed a significant increase in serum lipids,FBG,INS levels,and the HOMA-IR index (P<0.05). The orange-red lipid droplets in liver tissue increased,fat vacuoles were apparent,and TG levels were significantly increased. ApoA-Ⅰ mRNA and protein expression levels were significantly reduced,whereas GRP78,SREBP-1c,ACC1,and FASN mRNA expression levels were increased,GRP78,SREBP-1c,ACC1,and FASN protein levels and the IRE1,JNK,IRS1,and Akt phosphorylation degree were increased (P<0.05). The serum TG,HDL-C,LDL-C,FBG,and INS levels and the HOMA-IR index in the WT+HFD group were significantly reduced after administering modified XSLJZ (P<0.05). The orange-red lipid droplets in liver tissue were significantly reduced,fat vacuolization was alleviated,and TG levels were significantly reduced,ApoA-Ⅰ mRNA and protein expression levels were significantly increased,whereas GRP78,SREBP-1c,ACC1,and FASN mRNA expression levels were reduced,GRP78,SREBP-1c,ACC1,and FASN protein expression levels and the IRE1,JNK,IRS1,and Akt phosphorylation degree were reduced (P<0.05). Compared to the WT+HFD group,the TG,LDL-C,and FBG levels and HOMA-IR index in the serum of the apoA-Ⅰ-/-+HFD group were significantly increased,whereas the HDL-C levels were significantly decreased (P<0.05). Diffuse orange-red lipid droplets in liver tissue and a significant increase in fat vacuoles were observed. Furthermore,TG levels were significantly increased,SREBP-1c,ACC1,FASN mRNA,SREBP-1c,and ACC1 protein expression levels and IRE1,JNK,IRS1,and Akt phosphorylation levels were significantly increased (P<0.05). Compared to the WT+HFD+XSLJZ group,the apoA-Ⅰ-/-+HFD+XSLJZ group showed a significant increase in serum TG,LDL-C,FBG,and INS levels,and the HOMA-IR index,whereas HDL-C levels decreased significantly (P<0.05). The deposition of orange-red lipid droplets in liver tissue improved,and TG levels significantly decreased,GRP78,SREBP-1c,ACC1,and FASN mRNA expression levels,GRP78,SREBP-1c,and ACC1 protein levels,and IRE1,JNK,IRS1,and Akt phosphorylation levels increased (P<0.05). Conclusion Modified XSLJZ improves liver glucose and lipid metabolism disorder by regulating apoA-Ⅰ to alleviate endoplasmic reticulum stress.

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:This study constructs a strategic model for healthy city construction using Hubei Province as a case study,aiming to provide a reference for advancing healthy city initiatives.Methods:Utilizing grounded theory,we analyzed interview data from 9 cities in Hubei.Through open coding,principal axis coding,and selective coding,we identified and refined the strategic components for healthy city construction.Results:The strategies for healthy city construction in Hubei encompasses 30 initial categories,11 main categories,and 3 core categories:government initiative-led,departmental cooperation,and social co-construction and co-governance.This framework culminates in a theoretical model centered on sustainable construction,with the long-term improvement of population health as the ultimate goal.Conclusion:The strategies of government initiative-led,departmental cooperation,and social co-construction and co-governance function synergistically as guiding,implementing,and mobilizing frameworks for healthy city construction.By integrating these strategies,we can promote the sustainability of healthy cities and ultimately achieve long-term improvement of population health level.