Comparative analysis of bone turnover markers in bone marrow and peripheral blood: implications for osteoporosis.

INTRODUCTION: This study examines bone turnover marker (BTM) variations between bone marrow and peripheral blood in osteoporotic and non-osteoporotic patients. BTMs offer insights into bone remodeling, crucial for understanding osteoporosis. METHODS: A total of 133 patients were categorized into osteoporotic and non-osteoporotic cohorts. BTMs-C-telopeptide cross-linked type 1 collagen (ß-CTX), serum osteocalcin (OC), Procollagen type I N-propeptide (P1NP), 25(OH)D-were measured in bone marrow and peripheral blood. Lumbar spine bone mineral density (BMD) was assessed. RESULTS: Osteoporotic patients exhibited elevated ß-CTX and OC levels in peripheral blood, indicating heightened bone resorption and turnover. ß-CTX levels in osteoporotic bone marrow were significantly higher. Negative correlations were found between peripheral blood ß-CTX and OC levels and lumbar spine BMD, suggesting their potential as osteoporosis severity indicators. No such correlations were observed with bone marrow markers. When analyzing postmenopausal women separately, we obtained consistent results. CONCLUSIONS: Elevated ß-CTX and OC levels in osteoporotic peripheral blood highlight their diagnostic significance. Negative ß-CTX and OC-BMD correlations underscore their potential for assessing osteoporosis severity. Discrepancies between peripheral blood and bone marrow markers emphasize the need for further exploration. This research advances our understanding of BTM clinical applications in osteoporosis diagnosis and treatment.

CCL21 and CLDN11 Are Key Driving Factors of Lymph Node Metastasis in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. Understanding the molecular mechanisms of GC metastasis is crucial for improving patient survival outcomes. METHODS: RNA sequencing and analysis were performed on tissue samples from primary and lymph node metastatic lesions of gastric cancer. Differential gene analysis and functional pathway analysis were conducted. Immune infiltrating environment and protein expression levels were evaluated using immunohistochemistry. Cell experiments were conducted to investigate the role of CCL21 in GC metastasis. RESULTS: ACTG2, CNN1, DES, MUC6, and PGC were significantly upregulated in primary tumor cells, while CCL21, MS4A1, CR2, CLDN11, and FDCSP were significantly upregulated in metastatic tumor cells. Functional pathway analysis revealed enrichment in pathways related to immune response. CLDN11 and CCL21 were found to play important roles in promoting gastric cancer metastasis. Cell experiments confirmed the role of CCL21 in promoting GC cell growth and metastasis. CCL21 is highly expressed in GC tissues and binds to CCR7, leading to upregulation of CLDN11. This results in GC-lymph node metastasis and abnormal activation of immune cells (B cells and CD4+ T cells). CONCLUSION: Inhibition of CCL21 and CLDN11 proteins may be a promising strategy for treating GC and preventing lymph node metastasis. These findings provide specific molecular markers for early lymph node metastases of GC, which can aid in developing treatment strategies and predicting patient prognosis.

Optimizing Levothyroxine Replacement: A Precision Dosage Model for Post-Thyroidectomy Patients.

Background: Thyroidectomy is commonly performed for benign or malignant thyroid tumors, often resulting in hypothyroidism. Levothyroxine (LT4) supplementation is crucial to maintain hormone levels within the normal range and suppress TSH for cancer control. However, determining the optimal dosage remains challenging, leading to uncertain outcomes and potential side effects. Methods: We analyzed clinical examination data from 510 total thyroidectomy patients, including demographic information, blood tests, and thyroid function. Using R, we applied data preprocessing techniques and identified 274 samples with 98 variables. Principal Component Analysis, correlation analysis, and regression analysis were conducted to identify factors associated with optimal LT4 dosage. Results: The analysis revealed that only eight variables significantly influenced the final satisfactory dosage of LT4 in tablets: Benign0/Malignant1 (benign or malignant), BQB (electrophoretic albumin ratio), TP (total protein), FDP (fibrin degradation products), TRAB_1 (thyroid-stimulating hormone receptor antibody), PT (prothrombin time), MONO# (monocyte count), and HCV0C (hepatitis C antibody). The resulting predictive model was: . Conclusion: Parameters such as benign/malignant status, TRAB_1, and BQB ratio during medication can serve as observational indicators for postoperative LT4 dosage. The calculated linear model can predict the LT4 dosage for patients after thyroidectomy, leading to improved treatment effectiveness and conserving medical resources.

Quartet RNA reference materials improve the quality of transcriptomic data through ratio-based profiling.

Certified RNA reference materials are indispensable for assessing the reliability of RNA sequencing to detect intrinsically small biological differences in clinical settings, such as molecular subtyping of diseases. As part of the Quartet Project for quality control and data integration of multi-omics profiling, we established four RNA reference materials derived from immortalized B-lymphoblastoid cell lines from four members of a monozygotic twin family. Additionally, we constructed ratio-based transcriptome-wide reference datasets between two samples, providing cross-platform and cross-laboratory 'ground truth'. Investigation of the intrinsically subtle biological differences among the Quartet samples enables sensitive assessment of cross-batch integration of transcriptomic measurements at the ratio level. The Quartet RNA reference materials, combined with the ratio-based reference datasets, can serve as unique resources for assessing and improving the quality of transcriptomic data in clinical and biological settings.

Multi-omics data integration using ratio-based quantitative profiling with Quartet reference materials.

Characterization and integration of the genome, epigenome, transcriptome, proteome and metabolome of different datasets is difficult owing to a lack of ground truth. Here we develop and characterize suites of publicly available multi-omics reference materials of matched DNA, RNA, protein and metabolites derived from immortalized cell lines from a family quartet of parents and monozygotic twin daughters. These references provide built-in truth defined by relationships among the family members and the information flow from DNA to RNA to protein. We demonstrate how using a ratio-based profiling approach that scales the absolute feature values of a study sample relative to those of a concurrently measured common reference sample produces reproducible and comparable data suitable for integration across batches, labs, platforms and omics types. Our study identifies reference-free 'absolute' feature quantification as the root cause of irreproducibility in multi-omics measurement and data integration and establishes the advantages of ratio-based multi-omics profiling with common reference materials.

High-dimensional analysis reveals an immune atlas and novel neutrophil clusters in the lungs of model animals with Actinobacillus pleuropneumoniae-induced pneumonia.

Due to the increase in bacterial resistance, improving the anti-infectious immunity of the host is rapidly becoming a new strategy for the prevention and treatment of bacterial pneumonia. However, the specific lung immune responses and key immune cell subsets involved in bacterial infection are obscure. Actinobacillus pleuropneumoniae (APP) can cause porcine pleuropneumonia, a highly contagious respiratory disease that has caused severe economic losses in the swine industry. Here, using high-dimensional mass cytometry, the major immune cell repertoire in the lungs of mice with APP infection was profiled. Various phenotypically distinct neutrophil subsets and Ly-6C+ inflammatory monocytes/macrophages accumulated post-infection. Moreover, a linear differentiation trajectory from inactivated to activated to apoptotic neutrophils corresponded with the stages of uninfected, onset, and recovery of APP infection. CD14+ neutrophils, which mainly increased in number during the recovery stage of infection, were revealed to have a stronger ability to produce cytokines, especially IL-10 and IL-21, than their CD14- counterparts. Importantly, MHC-II+ neutrophils with antigen-presenting cell features were identified, and their numbers increased in the lung after APP infection. Similar results were further confirmed in the lungs of piglets infected with APP and Klebsiella pneumoniae infection by using a single-cell RNA-seq technique. Additionally, a correlation analysis between cluster composition and the infection process yielded a dynamic and temporally associated immune landscape where key immune clusters, including previously unrecognized ones, marked various stages of infection. Thus, these results reveal the characteristics of key neutrophil clusters and provide a detailed understanding of the immune response to bacterial pneumonia.

The critical role of platelet in cancer progression and metastasis.

Platelets play a crucial role in cancer blood metastasis. Various cancer-related factors such as Toll-like receptors (TLRs), adenosine diphosphate (ADP) or extracellular matrix (ECM) can activate these small particles that function in hemostasis and thrombosis. Moreover, platelets induce Epithelial Mesenchymal Transition (EMT) to promote cancer progression and invasiveness. The activated platelets protect circulating tumor cells from immune surveillance and anoikis. They also mediate tumor cell arrest, extravasation and angiogenesis in distant organs through direct or indirect modulation, creating a metastatic microenvironment. This review summarizes the recent advances and progress of mechanisms in platelet activation and its interaction with cancer cells in metastasis.

Identification of RAC1 in promoting brain metastasis of lung adenocarcinoma using single-cell transcriptome sequencing.

This study aims to give a new perspective to the biomarkers in the lung adenocarcinoma (LUAD) brain metastasis, pathways involved and potential therapeutics. We performed a comprehensive single-cell level transcriptomic analysis on one LUAD patient with circulating tumor cells (CTCs), primary tumor tissue and metastatic tumor tissue using scRNA-seq approach to identify metastasis related biomarkers. Further scRNA-seq were performed on 7 patients to validate the cancer metastatic hallmark. with single cells collected from either metastatic or primary LUAD tissues. Pathological and functional studies were also performed to evidence the critical role of RAC1 in the LUAD metastasis. Hallmark gene was verified based on immunohistochemistry staining, cytological experiment, survival information from The Cancer Genome Atlas (TCGA), and staining results from Human Protein Atlas (HPA) databases. PCA analysis revealed that CTCs were in the intermediate place between the metastatic group and primary group. In the unsupervised clustering analysis CTCs were closer to one of the metastatic tumor cells, implying heterogeneity of the metastatic tumor and origin of the CTCs were from metastatic site. Transitional phase related gene analysis identified RAC1 was enriched in metastatic tumor tissue (MTT) preferred gene set functioning as regulated cell death and apoptosis as well as promoted macromolecule organization. Compared with normal tissue, expression levels of RAC1 increased significantly in LUAD tissue based on HPA database. High expression of RAC1 predicts worse prognosis and higher-risk. EMT analysis identified the propensity of mesenchymal state in primary cells while epithelial signals were higher in the metastatic site. Functional clustering and pathway analyses suggested genes in RAC1 highly expressed cells played critical roles in adhesion, ECM and VEGF signaling pathways. Inhibition of RAC1 attenuates the proliferation, invasiveness and migration ability of lung cancer cells. Besides, through MRI T2WI results, we proved that RAC1 can promote brain metastasis in the RAC1-overexpressed H1975 cell burden nude mouse model. RAC1 and its mechanisms might promote drug design against LUAD brain metastasis.

Metagenomic association analysis of cognitive impairment in community-dwelling older adults.

The gut microbiota is reportedly involved in neurodegenerative disorders, and exploration of differences in the gut microbiota in different cognitive status could provide clues for early detection and intervention in cognitive impairment. Here, we used data from the Taizhou Imaging Study (N = 516), a community-based cohort, to compare the overall structure of the gut microbiota at the species level through metagenomic sequencing, and to explore associations with cognition. Interestingly, bacteria capable of producing short-chain fatty acids (SCFAs), such as Bacteroides massiliensis, Bifidobacterium pseudocatenulatum, Fusicatenibacter saccharivorans and Eggerthella lenta, that can biotransform polyphenols, were positively associated with better cognitive performance (p < 0.05). Although Diallister invisus and Streptococcus gordonii were not obviously related to cognition, the former was dominant in individuals with mild cognitive impairment (MCI), while the later was more abundant in cognitively normal (CN) than MCI groups, and positively associated with cognitive performance (p < 0.05). Functional analysis further supported a potential role of SCFAs and lactic acid in the association between the gut microbiota and cognition. The significant associations persisted after accounting for dietary patterns. Collectively, our results demonstrate an association between the gut microbiota and cognition in the general population, indicating a potential role in cognitive impairment. The findings provide clues for microbiome biomarkers of dementia, and insight for the prevention and treatment of dementia.

The effects of altered DNA damage repair genes on mutational processes and immune cell infiltration in esophageal squamous cell carcinoma.

BACKGROUND: Defects in DNA damage repair (DDR) pathways lead to genomic instability and oncogenesis. DDR deficiency is prevalent in esophageal squamous cell carcinoma (ESCC), but the effects of DDR alterations on mutational processes and tumor immune microenvironment in ECSS remain unclear. METHODS: Whole-exome and transcriptome sequencing data of 45 ESCC samples from Taizhou, China, were used to identify genomic variations, gene expression modulation in DDR pathways, and the abundance of tumor-infiltrating immune cells. Ninety-six ESCC cases from The Cancer Genome Atlas (TCGA) project were used for validation. RESULTS: A total of 57.8% (26/45) of the cases in the Taizhou data and 70.8% (68/96) of the cases in the TCGA data carried at least one functional impact DDR mutation. Mutations in the DDR pathways were associated with a high tumor mutation burden. Several DDR deficiency-related mutational signatures were discovered and were associated with immune cell infiltration, including T cells, monocytes, dendritic cells, and mast cells. The expression levels of two DDR genes, HFM1 and NEIL1, were downregulated in ESCC tumor tissues and had an independent effect on the infiltration of mast cells. In the Taizhou data, increased expression of HFM1 was associated with a poor prognosis, and the increased expression of NEIL1 was associated with a good outcome, but no reproducible correlation was observed in the TCGA data. CONCLUSION: This research demonstrated that DDR alterations could impact mutational processes and immune cell infiltration in ESCC. The suppression of HFM1 and NEIL1 could play a crucial role in ESCC progression and may also serve as prognostic markers.

Identification of Candidate Therapeutic Genes for More Precise Treatment of Esophageal Squamous Cell Carcinoma and Adenocarcinoma.

The standard therapy administered to patients with advanced esophageal cancer remains uniform, despite its two main histological subtypes, namely esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinoma (AC), are being increasingly considered to be different. The identification of potential drug target genes between SCC and AC is crucial for more effective treatment of these diseases, given the high toxicity of chemotherapy and resistance to administered medications. Herein we attempted to identify and rank differentially expressed genes (DEGs) in SCC vs. AC using ensemble feature selection methods. RNA-seq data from The Cancer Genome Atlas and the Fudan-Taizhou Institute of Health Sciences (China). Six feature filters algorithms were used to identify DEGs. We built robust predictive models for histological subtypes with the random forest (RF) classification algorithm. Pathway analysis also be performed to investigate the functional role of genes. 294 informative DEGs (87 of them are newly discovered) have been identified. The areas under receiver operator curve (AUC) were higher than 99.5% for all feature selection (FS) methods. Nine genes (i.e., ERBB3, ATP7B, ABCC3, GALNT14, CLDN18, GUCY2C, FGFR4, KCNQ5, and CACNA1B) may play a key role in the development of more directed anticancer therapy for SCC and AC patients. The first four of them are drug targets for chemotherapy and immunotherapy of esophageal cancer and involved in pharmacokinetics and pharmacodynamics pathways. Research identified novel DEGs in SCC and AC, and detected four potential drug targeted genes (ERBB3, ATP7B, ABCC3, and GALNT14) and five drug-related genes.

Effect of Rehabilitation Training Based on Automatic Extraction Algorithm on Knee Anterior Cruciate Ligament Injury Caused by Exercise.

Objective: In order to explore the effect of rehabilitation training based on automatic extraction algorithm on knee anterior cruciate ligament reconstruction under arthroscopy. Methods: 81 patients with anterior cruciate ligament injury were randomly divided into observation group (42 cases) and control group (39 cases). The control group was given routine nursing, while the observation group was given rehabilitation training guidance based on automatic extraction algorithm. Lysholm score, HSS score, and range of motion of knee joint extension and flexion were used to evaluate the knee joint function before and after operation in the two groups. The quality of life of the two groups was evaluated by the concise health survey scale. The results showed that 50% of deep venous thrombosis occurred on the first day and 30% on the second day after operation. There was no significant difference in preoperative Lysholm score, HSS score, and knee flexion activity between the observation group and the control group (P > 0.01). After 1-month, 5-month, and 1-year follow-up, the effective rate of knee function recovery in the observation group was significantly better than that in the control group. Lysholm score, HSS score, and knee extension and flexion activity were significantly different from those in the control group (P < 0.01). The postoperative SF-36 quality of life score of the observation group was significantly higher than that of the control group, indicating that the quality of life of the observation group was significantly better than that of the control group. Therefore, early postoperative rehabilitation training guidance based on automatic extraction algorithm can improve local blood circulation and improve knee function and reduce pain, so as to promote the early recovery of patients.

Calcitriol ameliorates renal injury with high-salt diet-induced hypertension by upregulating GLIS2 expression and AMPK/mTOR-regulated autophagy.

The goal of the present study was to investigate the protective effect of calcitriol on high-salt diet-induced hypertension. The hypertension rat model was established by a long-term high-salt diet (8% NaCl). Rats were treated with calcitriol, losartan, or their combination. Histological staining was used to confirm renal pathology. Global transcriptome analysis of renal tissues was performed, and the mechanism of the therapeutic effect of calcitriol was analysed by functional annotation and pathway analysis of the differentially expressed genes (DEGs) as well as by Western blotting analysis. The core genes for potential therapeutic regulation were identified through the coexpression gene network. For in vitro HK-2 cell experiments, small interfering RNA (siRNA) was used to knockdown key a transcription factor (TF) Glis2 to validate the therapeutic target of calcitriol. MAPK1 and CXCL12 expression was downregulated and the apoptosis pathway was significantly enriched by calcitriol treatment. The western blotting results showed that calcitriol treatment increased AMPK phosphorylation and decreased downstream mTOR phosphorylation, which was accompanied by a decrease in autophagy protein p62 expression and an increase in LC3-II/I expression. GLIS2 was identified as a specific therapeutic target for calcitriol. GLIS2 expression was upregulated by calcitriol and confirmed by HK-2 cells in vitro. Our omics data show that calcitriol can alleviate oxidative stress and fibrosis. Moreover, calcitriol can regulate the CXCL12/ERK1/2 cascade to inhibit the inflammatory response and renal cell apoptosis and induce renal autophagy through the AMPK/mTOR pathway. Our study partially elucidate the pathogenesis and treatment mechanism underlying hypertension, and provide new insights into the treatment of hypertension.

Environmental risk factors and genetic markers of Kaposi's sarcoma-associated herpesvirus infection among Uygur population in Xinjiang, China.

Kaposi sarcoma-associated herpesvirus (KSHV) is endemic in Xinjiang, China. Determinants of KSHV seropositivity among high-risk groups are not well understood. We seek to identify genetic and environmental predisposing factors for KSHV infection among Uygurs in this endemic region. A cross-sectional study was performed among the Uygur population in Xinjiang, China. KSHV-antibodies were detected using immunofluorescence assay (IFA) and human leukocyte antigen (HLA) alleles were genotyped. Univariate and multivariate logistic regression analyses were applied to explore the environmental and genetic risk factors of KSHV seropositivity. Finally, a total of 721 participants were included. The seroprevalence of KSHV was 24.1% among this population. Sweet-food preference (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.03-3.34), and coronary heart disease (OR 1.91, 95%CI 1.24-2.94) were statistically correlated with KSHV infection. HLA-DQB1*06:09 were found to significantly increase the risk of KSHV infection under all 3 models (ORAllelic = 4.06; ORDominant = 3.27; and ORRecessive = 8.06). Six SNPs (SNP0260, SNP0361, SNP0797, SNP0852, SNP1159, and SNP1375) in the DQB1 and DRB1 region and haploid type GTCTAACTAATC in block 17 were statistically associated with KSHV infection. We demonstrated that genetic variations in HLA-DQB1/DRB1 and environmental risk factors were strongly associated with KSHV infection among this population.

A machine learning-based approach to predicting the malignant and metastasis of thyroid cancer.

Background: Thyroid Cancer (TC) is the most common malignant disease of endocrine system, and its incidence rate is increasing year by year. Early diagnosis, management of malignant nodules and scientific treatment are crucial for TC prognosis. The first aim is the construction of a classification model for TC based on risk factors. The second aim is the construction of a prediction model for metastasis based on risk factors. Methods: We retrospectively collected approximately 70 preoperative demographic and laboratory test indices from 1735 TC patients. Machine learning pipelines including linear regression model ridge, Logistic Regression (LR) and eXtreme Gradient Boosting (XGBoost) were used to select the best model for predicting deterioration and metastasis of TC. A comprehensive comparative analysis with the prediction model using only thyroid imaging reporting and data system (TI-RADS). Results: The XGBoost model achieved the best performance in the final thyroid nodule diagnosis (AUC: 0.84) and metastasis (AUC: 0.72-0.77) predictions. Its AUCs for predicting Grade 4 TC deterioration and metastasis reached 0.84 and 0.97, respectively, while none of the AUCs for Only TI-RADS reached 0.70. Based on multivariate analysis and feature selection, age, obesity, prothrombin time, fibrinogen, and HBeAb were common significant risk factors for tumor progression and metastasis. Monocyte, D-dimer, T3, FT3, and albumin were common protective factors. Tumor size (11.14 ± 7.14 mm) is the most important indicator of metastasis formation. In addition, GGT, glucose, platelet volume distribution width, and neutrophil percentage also contributed to the development of metastases. The abnormal levels of blood lipid and uric acid were closely related to the deterioration of tumor. The dual role of mean erythrocytic hemoglobin concentration in TC needs to be verified in a larger patient cohort. We have established a free online tool (http://www.cancer-thyroid.com/) that is available to all clinicians for the prognosis of patients at high risk of TC. Conclusion: It is feasible to use XGBoost algorithm, combined with preoperative laboratory test indexes and demographic characteristics to predict tumor progression and metastasis in patients with TC, and its performance is better than that of Only using TI-RADS. The web tools we developed can help physicians with less clinical experience to choose the appropriate clinical decision or secondary confirmation of diagnosis results.

Calcitriol ameliorates damage in high-salt diet-induced hypertension: Evidence of communication with the gut-kidney axis.

Several studies have established a link between high-salt diet, inflammation, and hypertension. Vitamin D supplementation has shown anti-inflammatory effects in many diseases; gut microbiota is also associated with a wide variety of cardiovascular diseases, but potential role of vitamin D and gut microbiota in high-salt diet-induced hypertension remains unclear. Therefore, we used rats with hypertension induced by a high-salt diet as the research object and analyzed the transcriptome of their tissues (kidney and colon) and gut microbiome to conduct an overall analysis of the gut-kidney axis. We aimed to confirm the effects of high salt and calcitriol on the gut-kidney immune system and the composition of the intestinal flora. We demonstrate that consumption of a high-salt diet results in hypertension and inflammation in the colon and kidney and alteration of gut microbiota composition and function. High-salt diet-induced hypertension was found to be associated with seven microbial taxa and mainly associated with reduced production of the protective short-chain fatty acid butyrate. Calcitriol can reduce colon and kidney inflammation, and there are gene expression changes consistent with restored intestinal barrier function. The protective effect of calcitriol may be mediated indirectly by immunological properties. Additionally, the molecular pathways of the gut microbiota-mediated blood pressure regulation may be related to circadian rhythm signals, which needs to be further investigated. An innovative association analysis of the microbiota may be a key strategy to understanding the association between gene patterns and host.

Single-cell transcriptomic analysis reveals the critical molecular pattern of UV-induced cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer characterized by high invasiveness, heterogeneity, and mainly occurs in the ultraviolet (UV)-exposed regions of the skin, but its pathogenesis is still unclear. Here, we generated single-cell transcriptome profiles for 350 cells from six primary UV-induced cSCCs, together with matched adjacent skin samples, and three healthy control skin tissues by single-cell RNA-sequencing technology based on Smart-seq2 strategy. A series of bioinformatics analyses and in vitro experiments were used to decipher and validate the critical molecular pattern of cSCC. Results showed that cSCC cells and normal keratinocytes were significantly distinct in gene expression and chromosomal copy number variation. Furthermore, cSCC cells exhibited 18 hallmark pathways of cancer by gene set enrichment analysis. Differential expression analysis demonstrated that many members belonging to S100 gene family, SPRR gene family, and FABP5 were significantly upregulated in cSCC cells. Further experiments confirmed their upregulation and showed that S100A9 or FABP5 knockdown in cSCC cells inhibited their proliferation and migration through NF-κB pathway. Taken together, our data provide a valuable resource for deciphering the molecular pattern in UV-induced cSCC at a single-cell level and suggest that S100A9 and FABP5 may provide novel targets for therapeutic intervention of cSCC in the future.

Negative correlation between endoglin levels and coronary atherosclerosis.

BACKGROUND: Coronary artery disease (CAD) is a common cardiovascular disease, and abnormal blood lipid metabolism is an important risk factor. Transforming growth factor-ß (TGF-ß) and its receptor (TGF-ßR) can inhibit the release of inflammatory factors through the SMAD pathway-mediated immune response, thereby suppressing the progression of CAD. Endoglin (TGF-ßRIII), a TGF-ßR family homologous receptor protein, is directly involved in the immunoregulatory process, but the exact mechanism is unclear. This study aimed to clarify the pathophysiological effects of endoglin on the development of atherosclerosis and to explore the mechanism of the signalling pathway. METHODS: We downloaded the GEO dataset to perform a functional analysis of SMAD family activity and TGF-ß receptor protein expression in the monocyte expression profiles of patients with familial hyperlipidaemia (FH). The effect of endoglin on endothelial cell proliferation, migration, and apoptosis was examined by disrupting the endoglin gene in human umbilical vein endothelial cells (HUVECs) and validated by western blotting. The related genes and pathways regulated by endoglin were obtained by analysing the sequencing data. RESULTS: Research has shown that interference with endoglin can promote the proliferation and migration and significantly inhibit the apoptosis of vascular endothelial cells. Interference with endoglin particularly encourages the expression of VEGFB in vascular endothelial cells. CONCLUSION: The endoglin gene in vascular endothelial cells regulates the PI3K-Akt, Wnt, TNF, and cellular metabolism pathways by activating the SMAD pathway. RAB26, MR1, CCL2, SLC29A4, IBTK, VEGFB, and GOLGA8B play critical roles. Endoglin interacts closely with 11 proteins such as CCL2 and SEPRINE1, which participate in the vital pathway of plaque formation. Interference with endoglin can alter the course of coronary atherosclerosis.