1.Molecular Mechanism of Astragali Radix and Hedyotis diffusa in Regulating LINC01134-CTCF-p21 Axis to Inhibit Lung Adenocarcinoma Proliferation
Haipeng SUN ; He ZHUANG ; Xue LIU ; Siyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):131-138
ObjectiveTo explore the interaction and competitive binding of Homo sapiens long intergenic non-protein-coding RNA 1134 (LINC01134) to CCCTC-binding factor CTCF, affecting the transcription of cyclin-dependent kinase inhibitor (p21) and influencing the proliferation of A549 cells, in order to investigate the possible mechanism of Astragali Radix and Hedyotis diffusa (A-H) in inhibiting A549 proliferation by regulating this axis. MethodsRNA-binding protein immunoprecipitation (RIP) assays were conducted to examine the interaction between LINC01134 and CTCF, and chromatin immunoprecipitation (ChIP) assays were used to study the effect of LINC01134 overexpression on the interaction between CTCF and p21. Stable A549 cell lines (oe-NC and oe-LINC01134) were established using lentiviral transfection, and each group was treated with 10% A-H drug-containing serum. Real-time PCR and Western blot analyses were performed to detect the effects of A-H on the expression of LINC01134, CTCF, and p21 in A549 cells. Cell counting kit-8 (CCK-8) and colony formation assays were used to assess the effects of A-H on A549 cell proliferation via LINC01134. Flow cytometry was employed to evaluate the effects of A-H on the A549 cell cycle through LINC01134, and Western blot was used to detect changes in cell cycle proteins. ResultsCompared with the IgG group, the oe-CTCF group showed a significantly increased abundance of LINC01134 aggregates (P0.01). Compared with the oe-Vector group, p21 abundance in CTCF complexes was significantly reduced in the oe-LINC01134 group (P0.01). Compared with the 10% blank + oe-LINC01134 group, the 10% A-H + oe-LINC01134 group reversed the expression of LINC01134 and p21 (P0.05), but had no significant regulatory effect on CTCF. Compared with the 10% blank + oe-LINC01134 group, the 10% A-H + oe-LINC01134 group reversed cell viability at 72 h (P0.05), inhibited malignant proliferation (P0.05), and reversed the proportions of cells in the G0/G1 and S phases (P0.01). Furthermore, compared with the 10% blank + oe-LINC01134 group, the 10% A-H + oe-LINC01134 group reversed the expression of Cyclin D1, CDK4, Cyclin E, CDK2, phosphorylated retinoblastoma protein (p-Rb), and E2F transcription factor 3 (E2F3) (P0.01). ConclusionA-H regulates the LINC01134-CTCF-p21 axis to block the G1/S phase transition of A549 cell cycle, accelerate cellular senescence, and inhibit malignant proliferation.
2.Molecular Mechanism of Astragali Radix and Hedyotis diffusa in Regulating LINC01134-CTCF-p21 Axis to Inhibit Lung Adenocarcinoma Proliferation
Haipeng SUN ; He ZHUANG ; Xue LIU ; Siyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):131-138
ObjectiveTo explore the interaction and competitive binding of Homo sapiens long intergenic non-protein-coding RNA 1134 (LINC01134) to CCCTC-binding factor CTCF, affecting the transcription of cyclin-dependent kinase inhibitor (p21) and influencing the proliferation of A549 cells, in order to investigate the possible mechanism of Astragali Radix and Hedyotis diffusa (A-H) in inhibiting A549 proliferation by regulating this axis. MethodsRNA-binding protein immunoprecipitation (RIP) assays were conducted to examine the interaction between LINC01134 and CTCF, and chromatin immunoprecipitation (ChIP) assays were used to study the effect of LINC01134 overexpression on the interaction between CTCF and p21. Stable A549 cell lines (oe-NC and oe-LINC01134) were established using lentiviral transfection, and each group was treated with 10% A-H drug-containing serum. Real-time PCR and Western blot analyses were performed to detect the effects of A-H on the expression of LINC01134, CTCF, and p21 in A549 cells. Cell counting kit-8 (CCK-8) and colony formation assays were used to assess the effects of A-H on A549 cell proliferation via LINC01134. Flow cytometry was employed to evaluate the effects of A-H on the A549 cell cycle through LINC01134, and Western blot was used to detect changes in cell cycle proteins. ResultsCompared with the IgG group, the oe-CTCF group showed a significantly increased abundance of LINC01134 aggregates (P0.01). Compared with the oe-Vector group, p21 abundance in CTCF complexes was significantly reduced in the oe-LINC01134 group (P0.01). Compared with the 10% blank + oe-LINC01134 group, the 10% A-H + oe-LINC01134 group reversed the expression of LINC01134 and p21 (P0.05), but had no significant regulatory effect on CTCF. Compared with the 10% blank + oe-LINC01134 group, the 10% A-H + oe-LINC01134 group reversed cell viability at 72 h (P0.05), inhibited malignant proliferation (P0.05), and reversed the proportions of cells in the G0/G1 and S phases (P0.01). Furthermore, compared with the 10% blank + oe-LINC01134 group, the 10% A-H + oe-LINC01134 group reversed the expression of Cyclin D1, CDK4, Cyclin E, CDK2, phosphorylated retinoblastoma protein (p-Rb), and E2F transcription factor 3 (E2F3) (P0.01). ConclusionA-H regulates the LINC01134-CTCF-p21 axis to block the G1/S phase transition of A549 cell cycle, accelerate cellular senescence, and inhibit malignant proliferation.
3.Molecular Mechanism of Astragali Radix and Hedyotis diffusa Regulating Sp1-miR-582-3p-p27 Axis to Inhibit Lung Adenocarcinoma Proliferation
Haipeng SUN ; Lufan XU ; Xue LIU ; Siyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):116-124
ObjectiveTo investigate the effects of excessive activation of the Specific protein 1 (Sp1)-MicroRNA-582-3p (miR-582-3p)-cyclin-dependent kinase inhibitor (p27) axis on the cell cycle and proliferation of A549 lung adenocarcinoma cells at the cellular level, thereby investigating the possible mechanisms by which Astragali Radix and Hedyotis diffusa(A-H) regulate the axis to inhibit A549 cells proliferation. MethodsLentiviral plasmid transfection technology was used to obtain four stable A549 transgenic cell lines: shRNA-Sp1+LV-miR-582-3p mimic, shRNA-Sp1+LV-mNC, shRNA-NC+LV-miR-582-3p mimic, and shRNA-NC+LV-mNC. Real-time PCR was used to detect the effect of Sp1 on miR-582-3p expression in A549 lung adenocarcinoma cells. CCK-8 and colony formation assay were used to detect the effect of Sp1 on cell proliferation through miR-582-3p, while flow cytometry was used to detect the effect of Sp1 on cell cycle via miR-582-3p. Western blot was used to detect the effect of Sp1 on cyclin in A549 cells through miR-582-3p. CCK-8 was employed to detect the effects of different concentrations (5%, 10%, 20%, 40%, 80%) of A-H on A549 cell viability, and the optimal concentration was selected for subsequent mechanism exploration. Stable transgenic strains oe-Sp1 and control oe-Vector were constructed using the above-mentioned transfection techniques. Real-time PCR was then used to investigate the effect of A-H on miR-582-3p expression in A549 cells, while Western blot was employed to detect the effect of A-H on Sp1 and p27 expression in A549 lung adenocarcinoma cells. ResultsCompared with the shRNA-NC+LV-mNC group, the expression of miR-582-3p was significantly inhibited in the shRNA-Sp1+LV-mNC group (P<0.01). Compared with the shRNA-Sp1+LV-mNC group, the shRNA-Sp1+LV-miR-582-3p mimic group significantly reversed miR-582-3p expression (P<0.01), indicating that Sp1 has a significant regulatory effect on miR-582-3p. Compared with the shRNA-Sp1+LV-mNC group, the shRNA-Sp1+LV-miR-582-3p mimic group significantly reversed cell proliferation (P<0.01), suggesting that miR-582-3p can partially reverse the proliferative effect of Sp1 on A549 lung adenocarcinoma. Compared with the shRNA-Sp1+LV-mNC group, the shRNA-Sp1+LV-miR-582-3p mimic group showed a significant decrease in G0/G1 proportions, while the G2/M and S phase proportions increased significantly (P<0.01), indicating that miR-582-3p can partially reverse the effect of Sp1 on the A549 cell cycle. Compared with the shRNA-Sp1+LV-mNC group, the shRNA-Sp1+LV-miR-582-3p mimic group significantly reversed the expression of various proteins with the decrease of p27 and the increase of Cyclin D1, CDK4, Cyclin E, CDK2, p-Rb, and E2F3 (P<0.01), indicating that miR-582-3p can partially reverse the effect of Sp1 on the cell cycle of A549 lung adenocarcinoma. Compared with the blank group, the serum containing A-H significantly inhibited A549 cell viability in a concentration-dependent manner. Therefore, 10% A-H was selected for intervention of subsequent mechanism experiments. Compared with A-H+oe-Vector, A-H+oe-Sp1 significantly reversed the downregulation of Sp1, miR-582-3p, and the upregulation of p27 (P<0.01). This suggests that Sp1 can partially reverse the effects of A-H on miR-582-3p and p27 levels in A549 lung adenocarcinoma cells. ConclusionOveractivation of the Sp1-miR-582-3p-p27 axis significantly promotes the proliferation of A549 lung adenocarcinoma cells, and the potential mechanism of the inhibitory effect of A-H on the proliferation of A549 cells may be related to its inhibition on the overactivation of the Sp1-miR-582-3p-p27 axis.
4.Increasing trends of hyperglycemia and diabetes in treatment-naive people living with HIV in Shenzhen from 2013 to 2019: An emerging health concern.
Liqin SUN ; Haipeng ZHU ; Man RAO ; Fang ZHAO ; Yang ZHOU ; Lukun ZHANG ; Xia SHI ; Jianwei WU ; Yun HE ; Hongzhou LU ; Jiaye LIU
Chinese Medical Journal 2025;138(16):2043-2045
5.Real-time platelet P2Y12 receptor occupancy as a promising pharmacodynamics biomarker for bridging the gap between PK/PD of clopidogrel therapy.
Haipeng LI ; Yueming GU ; Yumeng ZHAO ; Aiyun XU ; Dong SUN ; Jingkai GU
Acta Pharmaceutica Sinica B 2025;15(1):484-493
Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y12 receptor through its active metabolite. However, the observed discrepancies between the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel present substantial challenges in individualizing of antiplatelet therapy. To address these challenges, a robust liquid chromatography-tandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y12 receptor occupancy. This method has been validated in animal models, providing a reliable link between individual PK profiles and PD effects. Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism, regulation of P2Y12 receptor expression, and platelet turnover. Moreover, it directly correlates with the inhibitory effect on platelet aggregation. The levels of platelet P2Y12 occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel, including dosage, drug-drug interactions (DDI), and type 2 diabetes mellitus (T2DM). As a normalized metric, platelet P2Y12 occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y12 signaling pathway in cases of abnormal on-treatment platelet reactivity.
6.The relationship between the expression of fibroblast growth factor 19 and insulin-like growth factor 1 in colorectal polyp tissues and the occurrence of colorectal adenomas
Hao WANG ; Haipeng WANG ; Yao YAO ; Dongyang WANG ; Ming CHEN ; Yanlai SUN ; Hao ZHANG ; Guangfeng DONG ; Zengjun LI
Chinese Journal of Oncology 2024;46(8):776-781
Objective:This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism.Method:Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted.Results:The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) μU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) μU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps ( OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions:There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.
7.The relationship between the expression of fibroblast growth factor 19 and insulin-like growth factor 1 in colorectal polyp tissues and the occurrence of colorectal adenomas
Hao WANG ; Haipeng WANG ; Yao YAO ; Dongyang WANG ; Ming CHEN ; Yanlai SUN ; Hao ZHANG ; Guangfeng DONG ; Zengjun LI
Chinese Journal of Oncology 2024;46(8):776-781
Objective:This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism.Method:Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted.Results:The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) μU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) μU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps ( OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions:There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.
8.Construction of multiclassification joint model to predict pathological classification of pulmonary ground-glass nodules based on radiomics
Ji KAI ; Yue JUNYAN ; Liu HAIPENG ; Sun MENGZHOU ; Liang XIAOYUN ; Zhang JING
Chinese Journal of Clinical Oncology 2024;51(19):1016-1022
Objective:To assess the predictive value of a combined multiclassification model for computed tomography(CT)in the patholo-gical analysis of ground-glass nodules(GGN).Methods:Pulmonary GGN lesions that were pathologically confirmed as invasive adenocar-cinoma(IAC),minimally invasive adenocarcinoma(MIA),adenocarcinoma in situ(AIS),and preinvasive lesions(PILs),were collected from pa-tients who were treated at The First Affiliated Hospital of Xinxiang Medical University between February 2019 and March 2023.A total of 324 nodules were retrospectively collected from 285 patients,and divided into three groups:infiltrating IAC,MIA,and PILs.Radiomics and clinical-CT features were selected through recursive feature elimination and univariate Logistic regression.Seven models were constructed using Logistic regression(LR),support vector machine(SVM),random forest(RF),and integrative learning(stacking).Results:The hybrid model combining clinical-CT-radiomics features and an integrative strategy showed superior predictive performance,with an accuracy of 0.791,precision of 0.788,specificity of 0.857,recall of 0.790,and F1-Score of 0.789.Conclusions:The multiclassification joint model based on CT-radiomics is effective in predicting pathological classification of pulmonary GGNs.This model aids in accurate imaging diagnosis and can provide a basis for optimizing treatment plans.
9.Analysis of the experience and procedural complications of trans-radial access versus trans-femoral access for hepatic arterial perfusion chemotherapy in patients with advanced hepatic malignancies:a retrospective study
Tianye LYU ; Mei LI ; Ji′an HE ; Qianfu SUN ; Li WANG ; Hao QIN ; Haipeng YU
Chinese Journal of Internal Medicine 2024;63(2):183-191
Objective:To analyze the differences between trans-radial access (TRA) and trans-femoral access (TFA) in hepatic arterial perfusion chemotherapy (HAIC) in terms of patient experience, postoperative complications, and patient preferences; explore whether TRA in HAIC is associated with better patient experience and compliance; and determine whether it is safer than TFA.Methods:The study was a retrospective cohort study of patients with advanced hepatocellular carcinoma and liver metastases from colorectal cancer treated with HAIC. We enrolled a total of 91 patients with advanced liver malignancies treated with HAIC from November 2022 to May 2023 in the Department of Interventional Therapy and Hepatobiliary Medicine at Tianjin Medical University Cancer Hospital. The patients were divided into three groups: group TRA ( n=20, receiving TRA HAIC only), group TFA ( n=33, receiving TFA HAIC only), and crossover group [ n=19, receiving TFA HAIC (Cross-TFA group) first, followed by TRA HAIC (Cross-TRA group)]. Meanwhile, to facilitate the expression of partial results, all patients receiving TRA HAIC were defined as the TRA-HAIC group ( n=39, TRA+Cross-TRA group), and all patients receiving TFA HAIC were defined as the TFA-HAIC group ( n=52, TFA+Cross-TFA group). The primary research index was the Quality of Life (QOL) visualization scale score. The secondary research index included approach-related and catheter-related adverse events, duration of surgery, and mean length of patient stay. We used various statistical methods such as Mann-Whitney U test, t-test, Chi-square test, Fisher′s exact test, univariate logistic regression analysis, and multi-factor analysis. Results:TRA patients had significantly lower QOL scores than TFA patients (all P<0.001). The QOL scores of the Cross-TRA group were significantly lower than those of the Cross-TFA group (pain at the puncture site Z=-3.24, P=0.001, others P<0.001). The QOL scores of the Cross-TRA group were compared with those of the TRA group, which showed that the scores of the Cross-TRA group in overall discomfort ( Z=-3.07, P=0.002), postoperative toilet difficulty ( Z=-2.12, P=0.034), and walking difficulty ( Z=-2.58, P=0.010) were significantly lower than those of the TRA group. Satisfaction scores were significantly higher in the Cross-TRA group than in the Cross-TFA group ( Z=-3.78, P<0.001), and patients were more likely to receive TRA HAIC as the next procedure ( χ2=30.42, P<0.001). In terms of mean length of stay, patients receiving TRA HAIC had a significantly lower mean length of stay than those receiving TFA HAIC (50.1±3.2 h vs. 58.4±6.4 h, t=7.98, P<0.001). The incidence of radial artery occlusion (RAO) as an approach-related adverse event was 15.4% (6/39) in the TRA-HAIC group, which was significantly higher than that in the TFA-HAIC group (15.4% vs. 0, χ2=8.56, P=0.005). Notably, multifactorial analysis of RAO-related factors showed that intraoperative enoxaparin use and patency of radial artery flow during pressure were significantly associated with a reduced risk of postoperative RAO ( P=0.037 for enoxaparin use and P=0.049 for pressure). Conclusions:With respect to procedure approach, TRA was significantly better than TFA in terms of patient satisfaction and mean length of stay. Through further process optimization and prevention of adverse reactions, the incidence of adverse reactions can be maintained at a relatively low level, so that patients can benefit from TRA in future operations in terms of cost-effectiveness and medical efficiency.
10.Experts consensus on the procedure of dental operative microscope in endodontics and operative dentistry.
Bin LIU ; Xuedong ZHOU ; Lin YUE ; Benxiang HOU ; Qing YU ; Bing FAN ; Xi WEI ; Lihong QIU ; Zhengwei HUANG ; Wenwei XIA ; Zhe SUN ; Hanguo WANG ; Liuyan MENG ; Bin PENG ; Chen ZHANG ; Shuli DENG ; Zhaojie LU ; Deqin YANG ; Tiezhou HOU ; Qianzhou JIANG ; Xiaoli XIE ; Xuejun LIU ; Jiyao LI ; Zuhua WANG ; Haipeng LYU ; Ming XUE ; Jiuyu GE ; Yi DU ; Jin ZHAO ; Jingping LIANG
International Journal of Oral Science 2023;15(1):43-43
The dental operative microscope has been widely employed in the field of dentistry, particularly in endodontics and operative dentistry, resulting in significant advancements in the effectiveness of root canal therapy, endodontic surgery, and dental restoration. However, the improper use of this microscope continues to be common in clinical settings, primarily due to operators' insufficient understanding and proficiency in both the features and established operating procedures of this equipment. In October 2019, Professor Jingping Liang, Vice Chairman of the Society of Cariology and Endodontology, Chinese Stomatological Association, organized a consensus meeting with Chinese experts in endodontics and operative dentistry. The objective of this meeting was to establish a standard operation procedure for the dental operative microscope. Subsequently, a consensus was reached and officially issued. Over the span of about four years, the content of this consensus has been further developed and improved through practical experience.
Humans
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Dentistry, Operative
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Consensus
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Endodontics
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Root Canal Therapy
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Dental Care

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