1.The mechanism of Prim-O-glucosylcimifugin in improving cholesterol metabolism in osteoarthritis chondrocytes via lncRNA NEAT1/miR-128-3p
Yanming LIN ; Haishui TU ; Shujie LAN ; Chao LI ; Shiyu LU ; Yue CHEN ; Changlong FU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):55-67
Objective:
To investigate the mechanism of action of Prim-O-glucosylcimifugin (POG) to improve cholesterol metabolism in osteoarthritic (OA) chondrocytes based on the long noncoding RNA nuclear-enriched transcript 1 (lncRNA NEAT1)/microRNA-128-3p (miR-128-3p) pathway.
Methods:
For in vivo experiments, 60 mice were divided into the normal, sham operation, model, and POG groups using the random number table method, with 15 mice per group. The osteoarthritis mouse model was constructed using the modified Hulth method in the model and POG groups. Mice in the POG group were administered 30 mg/(kg·d)POG by gavage. The other groups were administered an equal amount of normal saline for 8 weeks. The cartilage tissue structure of mice in each group was observed using hematoxylin and eosin staining. Real-time PCR was used to detect changes in the lncRNA NEAT1 and miR-128-3p mRNA expression levels in the cartilage tissues of mice. Western blotting was used to detect the protein expressions of ATP-binding cassette transporter A1 (ABCA1), liver X receptor β (LXRβ), matrix metalloprotein-3 (MMP-3), and B-lymphoblastoma-2-associated X protein (Bax) in articular cartilage of mice. An enzyme-linked immunosorbent assay was used to measure the tumor necrosis factor-α (TNF-α) content in the synovial fluid of mice. A biochemical microplate assay was used to measure the total cholesterol level in the synovial fluid of mice. The in vitro experiments were divided into the negative control, interleukin-1β(IL-1β), IL-1β+ POG, IL-1β+ oe-lncRNA NEAT1, IL-1β+ oe-lncRNA NEAT1 + POG, IL-1β + miR-128-3p inhibition, and IL-1β+ miR-128-3p inhibition+ POG groups. An OA model was established by inducing chondrocytes with IL-1β for 24 h, and 90 mg/L of POG and miR-128-3p inhibitor(50 nmol/L) were administered for 48 h as an intervention. lncRNA NEAT1 expression in chondrocytes was detected using fluorescence in situ hybridization. A dual luciferase assay was used to detect the targeting relationship between lncRNA NEAT1 and miR-128-3p. Lentiviral plasmids overexpressing lncRNA NEAT1 were used to transfect mouse chondrocytes. Real-time PCR was used to detect the effect of lncRNA NEAT1 overexpression on the mRNA level of miR-128-3p in chondrocytes. Western blotting was used to detect ABCA1, LXRβ, MMP-3, and Bax protein expression in chondrocytes after lncRNA NEAT1 overexpression and miR-128-3p inhibition.
Results:
POG significantly reduced OA cartilage tissue damage. Compared with the model group, the lncRNA NEAT1 mRNA level decreased, whereas the miR-128-3p mRNA level increased in the cartilage tissue of the POG group (P<0.05). Compared with the model group, ABCA1 and LXRβ protein expression increased in the POG group, whereas MMP-3 and Bax protein expression decreased (P<0.05). The TNF-α levels decreased in the POG group compared to the model group (P<0.05). Compared with the model group, the total cholesterol level in the synovial fluid of the joint of mice in the POG group decreased (P<0.05). The mean fluorescence intensity of lncRNA NEAT1 in the IL-1β+ POG group decreased compared with the IL-1β group (P<0.05). The relative luciferase activity in the miR-128-3p mimics group bound to the lncRNA NEAT1-WT plasmid decreased compared with the miR-128-3p negative control group (P<0.05). The lncRNA NEAT1 mRNA levels decreased, whereas the miR-128-3p mRNA levels increased in the IL-1β+ oe-lncRNA NEAT1 + POG group compared with the IL-1β+ oe-lncRNA NEAT1 group (P<0.05). Compared with the IL-1β+ POG group, ABCA1 and LXRβ protein expression decreased, whereas MMP-3 and Bax protein expression increased (P<0.05).
Conclusion
POG mediates lncRNA NEAT1/miR-128-3p to improve cholesterol metabolism in OA chondrocytes.
2.Idarucizumab for reversal of dabigatran etexilate-induced gastrointestinal bleeding
Qi LIN ; Shujie DONG ; Lei LI ; Kun WANG ; Junbao SHI ; Li YANG
Adverse Drug Reactions Journal 2025;27(1):53-55
An 82-year-old female patient with atrial fibrillation and heart failure was treated with dabigatran etexilate 110 mg twice daily for 6 years. Two months ago, the patient′s lower limb edema was aggravated and urine output was reduced. Considering the worsening of the patient′s heart failure, torasemide tablets and spironolactone tablets were given, but her symptoms were not improved. Two days ago, the patient had scattered petechiae on the whole skin, tarry stools, and reduced urine (200 ml daily). Laboratory tests showed hemoglobin (Hb) 63 g/l, prothrombin time (PT) 39.5 s, activated partial thromboplastin time (APTT) 117.2 s, thrombin time (TT) >300 s, and international normalized ratio (INR) 3.64; the fibrinogen (Fib) could not be measured. Coagulation dysfunction and gastrointestinal bleeding caused by dabigatran etexilate were considered. Dabigatran etexilate was discontinued, and intravenous infusion of idarucizumab injection (2.5 g) was given twice. Then gastrointestinal bleeding in the patient disappeared and laboratory tests showed PT 12.7 s, APTT 42.4 s, TT 18.8 s, INR 1.18, and Fib 2.67 g/L. After 8 days, the patient′s cardiac function was improved, the skin ecchymosis subsided, and laboratory tests showed Hb 84 g/L, PT 14 s, APTT 37.8 s, TT 41.2 s, INR 1.3, Fib 2.26 g/L, and negative fecal occult blood test.
3.Development and validation of a nomogram for predicting postoperative prognosis in gallbladder cancer patients based on the HALP score
Shujie HE ; Zhelong JIANG ; Lili WU ; Xuanhua LIN ; Lizhi LYU ; Yang CHENG ; Baipo ZHOU ; Fang YANG ; Jianwei CHEN
Chinese Journal of Hepatobiliary Surgery 2025;31(9):666-670
Objective:To analyze the effects of hemoglobin, albumin, lymphocyte and platelet count (HALP) scores on the survival of gallbladder cancer patients after radical surgery, and to construct a prognostic prediction model and evaluate based on HALP scores.Methods:The clinical data of 95 patients with gallbladder cancer who underwent surgical treatment in Fuzong Clinical Medical College of Fujian Medical University (the 900th Hospital) from January 2010 to December 2022 were retrospectively analyzed, including 40 males and 55 females, with the age of (63.3±12.2) years. All patients were divided into a low HALP group (HALP score ≤35.4, n=45) and a high HALP group (HALP score >35.4, n=50) based on the optimal cut-off value of 35.4 for predicting postoperative survival as determined by the receiver operating characteristic (ROC) curve. Survival curves were plotted by the Kaplan-Meier method, and survival comparisons were performed using the log-rank test. Univariate and multivariate Cox regression were used to analyze the effect of HALP score on survival after radical surgery in patients with gallbladder cancer. Based on the multifactorial results, nomogram was constructed to predict the survival of gallbladder cancer patients after radical surgery, and ROC curves, consistency indexes were evaluated in the model. Results:A total of 95 patients were followed up for 1-150 months, with a median of 13 months. The 1-, 3-, and 5-year postoperative cumulative survival rates of patients in the low HALP group were 56.2%, 31.2%, and 11.1%, respectively, which were lower than those of the high HALP group, which were 82.9%, 59.6%, and 40.7%, and the difference was statistically significant ( χ2=12.50, P<0.001). Based on multifactorial Cox regression analysis, preoperative total bilirubin ≥23 μmol/L, with lymph node metastasis, tumor TNM stage Ⅲ-Ⅳ, and postoperative incision infection were the risk factors for survival after radical surgery in patients with gallbladder cancer, and a HALP score of >35.4 and Child-Pugh A were protective factors (all P<0.05). Based on the results of multivariate Cox regression analysis to construct a nomogram for predicting overall survival after radical surgery in patients with gallbladder cancer, the consistency index between the prediction of the nomogram and the actual situation was 0.801 (95% CI: 0.752-0.850), and the area under the ROC curve for predicting overall survival was 0.812 (95% CI: 0.704-0.902). Conclusion:The preoperative high HALP score (HALP > 35.4) is a protective factor for survival after radical surgery in gallbladder cancer patients, and the nomogram constructed based on the HALP score for survival prediction after radical surgery for gallbladder cancer has high accuracy and can be used for the assessment of postoperative survival.
4.Summary of the best evidence for home nutrition management in patients after gastric cancer surgery
Ying ZENG ; Jinyi XIE ; Shujie LIN ; Lijing WEN ; Fangyan LU
Modern Clinical Nursing 2025;24(7):83-92
Objective To retrieve,evaluate and summarise the best evidence in home nutrition management for patients after gastric cancer surgery,so as to provide a reference for medical staff.Methods According to the"6S"mode of evidence-based resource retrieval,desktop work was conducted to search the databases of UpToDate,PubMed,Embase,Cochrane Library,Web of Science,China National Knowledge Infrastructure(CNKI),VIP database,Wanfang database,Scottish Intercollegiate Guidelines Network(SIGN),the website of National Institute for Health and Care Excellence(NICE),Guidelines International Network(GIN),National Guideline Clearinghouse(NGC),the website of Registered Nurses'Association of Ontario(RNAO),the guidelines website of Chinese Society of Clinical Oncology(CSCO),Physiotherapy Evidence Database(PEDro),National Comprehensive Cancer Network(NCCN),the website of China Medical Association(CMA),the website of American Society for Parenteral and Enteral Nutrition(ASPEN),the website of European Society for Clinical Nutrition and Metabolism(ESPEN),and Yimaitong for clinical guidelines,systematic evaluations,expert consensuses,clinical decisions,evidence summaries and randomised controlled trials(RCTs)in home nutrition management for the patients after gastric cancer surgery.The retrieved data was from 1st January,2014 to 30th June,2024.Two researchers who had systematic training in evidence-based nursing independently screened and evaluated the retrieved literature.Results A total of 13 documents were finally included,covering 5 clinical guidelines,5 expert consensuses,1 clinical decision and 2 RCT studies.Thirty-two pieces of the best evidence were summarised from seven aspects of nutritional follow-up,nutritional risk screening and assessment,health education of oral nutrition,health education of tube-fed enteral nutrition,health education of nutrient requirement,complication management and life management.Conclusion The evidence summarised in this study on home nutrition management for the patients after gastric cancer surgery can be used as a reference for medical staff.
5.Idarucizumab for reversal of dabigatran etexilate-induced gastrointestinal bleeding
Qi LIN ; Shujie DONG ; Lei LI ; Kun WANG ; Junbao SHI ; Li YANG
Adverse Drug Reactions Journal 2025;27(1):53-55
An 82-year-old female patient with atrial fibrillation and heart failure was treated with dabigatran etexilate 110 mg twice daily for 6 years. Two months ago, the patient′s lower limb edema was aggravated and urine output was reduced. Considering the worsening of the patient′s heart failure, torasemide tablets and spironolactone tablets were given, but her symptoms were not improved. Two days ago, the patient had scattered petechiae on the whole skin, tarry stools, and reduced urine (200 ml daily). Laboratory tests showed hemoglobin (Hb) 63 g/l, prothrombin time (PT) 39.5 s, activated partial thromboplastin time (APTT) 117.2 s, thrombin time (TT) >300 s, and international normalized ratio (INR) 3.64; the fibrinogen (Fib) could not be measured. Coagulation dysfunction and gastrointestinal bleeding caused by dabigatran etexilate were considered. Dabigatran etexilate was discontinued, and intravenous infusion of idarucizumab injection (2.5 g) was given twice. Then gastrointestinal bleeding in the patient disappeared and laboratory tests showed PT 12.7 s, APTT 42.4 s, TT 18.8 s, INR 1.18, and Fib 2.67 g/L. After 8 days, the patient′s cardiac function was improved, the skin ecchymosis subsided, and laboratory tests showed Hb 84 g/L, PT 14 s, APTT 37.8 s, TT 41.2 s, INR 1.3, Fib 2.26 g/L, and negative fecal occult blood test.
6.Summary of the best evidence for home nutrition management in patients after gastric cancer surgery
Ying ZENG ; Jinyi XIE ; Shujie LIN ; Lijing WEN ; Fangyan LU
Modern Clinical Nursing 2025;24(7):83-92
Objective To retrieve,evaluate and summarise the best evidence in home nutrition management for patients after gastric cancer surgery,so as to provide a reference for medical staff.Methods According to the"6S"mode of evidence-based resource retrieval,desktop work was conducted to search the databases of UpToDate,PubMed,Embase,Cochrane Library,Web of Science,China National Knowledge Infrastructure(CNKI),VIP database,Wanfang database,Scottish Intercollegiate Guidelines Network(SIGN),the website of National Institute for Health and Care Excellence(NICE),Guidelines International Network(GIN),National Guideline Clearinghouse(NGC),the website of Registered Nurses'Association of Ontario(RNAO),the guidelines website of Chinese Society of Clinical Oncology(CSCO),Physiotherapy Evidence Database(PEDro),National Comprehensive Cancer Network(NCCN),the website of China Medical Association(CMA),the website of American Society for Parenteral and Enteral Nutrition(ASPEN),the website of European Society for Clinical Nutrition and Metabolism(ESPEN),and Yimaitong for clinical guidelines,systematic evaluations,expert consensuses,clinical decisions,evidence summaries and randomised controlled trials(RCTs)in home nutrition management for the patients after gastric cancer surgery.The retrieved data was from 1st January,2014 to 30th June,2024.Two researchers who had systematic training in evidence-based nursing independently screened and evaluated the retrieved literature.Results A total of 13 documents were finally included,covering 5 clinical guidelines,5 expert consensuses,1 clinical decision and 2 RCT studies.Thirty-two pieces of the best evidence were summarised from seven aspects of nutritional follow-up,nutritional risk screening and assessment,health education of oral nutrition,health education of tube-fed enteral nutrition,health education of nutrient requirement,complication management and life management.Conclusion The evidence summarised in this study on home nutrition management for the patients after gastric cancer surgery can be used as a reference for medical staff.
7.Development and validation of a nomogram for predicting postoperative prognosis in gallbladder cancer patients based on the HALP score
Shujie HE ; Zhelong JIANG ; Lili WU ; Xuanhua LIN ; Lizhi LYU ; Yang CHENG ; Baipo ZHOU ; Fang YANG ; Jianwei CHEN
Chinese Journal of Hepatobiliary Surgery 2025;31(9):666-670
Objective:To analyze the effects of hemoglobin, albumin, lymphocyte and platelet count (HALP) scores on the survival of gallbladder cancer patients after radical surgery, and to construct a prognostic prediction model and evaluate based on HALP scores.Methods:The clinical data of 95 patients with gallbladder cancer who underwent surgical treatment in Fuzong Clinical Medical College of Fujian Medical University (the 900th Hospital) from January 2010 to December 2022 were retrospectively analyzed, including 40 males and 55 females, with the age of (63.3±12.2) years. All patients were divided into a low HALP group (HALP score ≤35.4, n=45) and a high HALP group (HALP score >35.4, n=50) based on the optimal cut-off value of 35.4 for predicting postoperative survival as determined by the receiver operating characteristic (ROC) curve. Survival curves were plotted by the Kaplan-Meier method, and survival comparisons were performed using the log-rank test. Univariate and multivariate Cox regression were used to analyze the effect of HALP score on survival after radical surgery in patients with gallbladder cancer. Based on the multifactorial results, nomogram was constructed to predict the survival of gallbladder cancer patients after radical surgery, and ROC curves, consistency indexes were evaluated in the model. Results:A total of 95 patients were followed up for 1-150 months, with a median of 13 months. The 1-, 3-, and 5-year postoperative cumulative survival rates of patients in the low HALP group were 56.2%, 31.2%, and 11.1%, respectively, which were lower than those of the high HALP group, which were 82.9%, 59.6%, and 40.7%, and the difference was statistically significant ( χ2=12.50, P<0.001). Based on multifactorial Cox regression analysis, preoperative total bilirubin ≥23 μmol/L, with lymph node metastasis, tumor TNM stage Ⅲ-Ⅳ, and postoperative incision infection were the risk factors for survival after radical surgery in patients with gallbladder cancer, and a HALP score of >35.4 and Child-Pugh A were protective factors (all P<0.05). Based on the results of multivariate Cox regression analysis to construct a nomogram for predicting overall survival after radical surgery in patients with gallbladder cancer, the consistency index between the prediction of the nomogram and the actual situation was 0.801 (95% CI: 0.752-0.850), and the area under the ROC curve for predicting overall survival was 0.812 (95% CI: 0.704-0.902). Conclusion:The preoperative high HALP score (HALP > 35.4) is a protective factor for survival after radical surgery in gallbladder cancer patients, and the nomogram constructed based on the HALP score for survival prediction after radical surgery for gallbladder cancer has high accuracy and can be used for the assessment of postoperative survival.
8.Clinical and Pathological Characteristics of Extrapleural Solitary Fibrous Tumor
Ying LIU ; Shujie SONG ; Lin WU
Journal of Kunming Medical University 2024;45(1):100-106
Objective To investigate the clinical and pathological characteristics of the extrapleural solitary fibrous tumor and the relevant differential diagnosis.Methods HE and immunohistochemical staining were performed on 26 samples of isolated fibrous tumors outside the pleura,and a comprehensive analysis was conducted based on the clinical and imaging data.Results The histological morphology of isolated fibrous tumors was diverse,with typical cases showing the irregular arrangement of oval or spindle shaped cells.In the stroma,thick collagen bands,antler like blood vessels,and peritubular transparent degeneration could be seen.The immunohistochemical staining demonstrated that the positive rates of STAT-6、CD34、Bcl-2、CD99、SMA were 96.2% 、92.3% 、92.3% 、76.9% and 26.9%,respectively.Conclusion SFT commonly occurs in the pleura and can also occur in other areas.Its histological characteristics and immunohistochemical phenotype help to clarify the diagnosis.However,when it occurs in uncommon anatomical sites,it is necessary to carefully and meticulously distinguish and comprehensively judge the clinical prognosis of key diseases that need to be distinguished or excluded..
9.Effect of Early Intervention of Yishen Huazhuo Prescription on Learning and Memory of Accelerated Aging SAMP8 Mice and Its Mechanism
Shujie ZAN ; Kai WANG ; Jiachun XU ; Weiming SUN ; Daoyan NI ; Linlin ZHANG ; Shuang LIU ; Yan MA ; Pengjuan XU ; Lin LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):91-99
ObjectiveTo investigate the impact of early intervention with Yishen Huazhuo prescription (YHP) on the learning and memory of accelerated aging model mice, as well as its underlying mechanism. MethodForty-eight 3-month-old male SAMP8 mice were randomly assigned into four groups, including the model group, low-dose YHP group, high-dose YHP group, and donepezil group. Additionally, 24 SAMR1 mice of the same age were divided into a control group and a YHP treatment control group, each consisting of 12 mice. The YHP groups received YHP at doses of 6.24 g·kg-1 and 12.48 g·kg-1, while the donepezil group was treated with donepezil at a dose of 0.65 mg·kg-1. The model group and control groups were given physiological saline. The mice were gavaged once daily for a duration of four weeks. Spatial learning and memory abilities of mice were assessed using the Morris water maze test. Immunofluorescence staining was employed to evaluate neuronal density as well as expression levels of M1 microglial (MG) polarization marker inducible nitric oxide synthase (iNOS) and M2 MG polarization marker arginase-1 (Arg-1) in the hippocampus region. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of pro-inflammatory factor interleukin 1β (IL-1β) and anti-inflammatory factor transforming growth factor-β1 (TGF-β1). Furthermore, Western blot analysis was conducted to determine expressions of amyloid β peptide1-42 (Aβ1-42) along with triggering receptor expressed on myeloid cells 2 (TREM2)/nuclear factor kappa B (NF-κB) signaling pathway-related proteins TREM2, phospho (p)-NF-κB p65, and phospho-inhibitory kappa B kinase β (IKKβ) in the hippocampus. ResultCompared with the control group, the model group exhibited a significantly prolonged escape latency (P<0.01), a significant reduction in neuron-specific nuclear protein (NeuN) expression in the hippocampus, a significant increase in iNOS expression in MG, and a significant decrease in Arg-1 expression. The serum IL-1β content was significantly increased, while the TGF-β1 content was significantly decreased. Additionally, there was a significant decrease in TREM2 expression in the hippocampus and significant increases in p-NF-κB p65, p-IKKβ, and Aβ1-42 expressions (P<0.05, P<0.01). However, no significant changes were observed in escape latency, times of crossing the platform, and hippocampal NeuN expression in the YHP treatment control group. Conversely, iNOS expression in MG as well as the hippocampal p-NF-κB p65, p-IKKβ, and Aβ1-42 expressions were significantly decreased. Furthermore, TREM2 expression was significantly increased (P<0.05, P<0.01). In comparison to the model group, the low-dose YHP group showed a significantly shortened escape latency and an increased number of crossing the platform (P<0.05, P<0.01). In the high-dose YHP group, the escape latency was significantly shortened (P<0.05). In the low-dose YHP group, high-dose YHP group, the expression of NeuN in the hippocampus was significantly increased, the expression of iNOS in MG was significantly decreased, and the expression of Arg-l was significantly increased. The serum IL-1β content was significantly decreased, while the TGF-β1 content was significantly increased. Furthermore, the expression of TREM2 in the hippocampus was significantly increased, and the expressions of p-NF-κB p65, p-IKKβ, and Aβ1-42 were significantly decreased (P<0.01). ConclusionEarly YHP intervention may promote the transformation of hippocampal MG from M1 to M2 by regulating the TREM2/NF-κB signaling pathway, reduce the release of neuroinflammatory factors, protect hippocampal neurons, and reduce the deposition of Aβ1-42, and finally delay the occurrence of learning and memory decline in SAMP8 mice.
10.Tougu Xiaotong Capsule alleviates cartilage degeneration in mice with knee osteoarthritis by modulating Nav1.7
Changlong FU ; Yanming LIN ; Shujie LAN ; Yue CHEN ; Chao LI ; Shiyu LU ; Qing LIN
Journal of Southern Medical University 2024;44(11):2074-2081
Objective To investigate the mechanism by which Tougu Xiaotong Capsule(TGXTC)alleviates chondrocyte degeneration in knee osteoarthritis(KOA).Methods Thirty 2-month-old C57BL/6 mouse models of KOA established using the Hulth method were randomized into model group,TGXTC group,and diclofenac sodium group and received treatment with saline,TGXTC(368 mg/kg),and diclofenac sodium(10 mg/kg)by gavage,respectively,with another 10 untreated mice as the blank control group.All interventions were administered 6 times a week for 4 weeks.After the treatments,structural changes in the cartilage tissue were observed with morphological staining,and Nav1.7 mRNA expression and the protein expression levels of Nav1.7,MMP-3,ADAMTS-5,and COX-2 were detected using RT-qPCR and Western blotting.Fluorescence in situ hybridization(FISH)was used to detect Nav1.7 expression in the chondrocytes.In cultured KOA chondrocytes,the effect of TGXTC and lentivirus-mediated Nav1.7 knockdown on MMP-3,MMP-13,ADAMTS-4,ADAMTS-5,and COX-2 protein expressions were assessed with Western blotting.Results In KOA mice treatments with TGXTC and diclofenac sodium both significantly alleviated structural damage of the cartilage layer,reduced Nav1.7 protein and mRNA expressions and lowered the expressions of MMP-3,ADAMTS-5,and COX-2 proteins in the cartilage tissues.FISH results indicated that TGXTC treatment significantly reduced IL-1β-induced Nav1.7 expression in the chondrocytes.In Nav1.7 knockdown experiment,Nav1.7 levels were significantly lower in IL-1β+sh-Nav1.7 group than in IL-1β group,and also lower in IL-1β+TGXTC group than in IL-1β+sh-Nav1.7+TGXTC group.TGXTC treatment significantly inhibited IL-1β-induced elevation of MMP-3,MMP-13,ADAMTS-4,ADAMTS-5 and COX-2 protein expressions in the chondrocytes,but its effects were strongly weakened by Nav1.7 knockdown.Conclusion TGXTC alleviates extracellular matrix metabolic disorder in KOA chondrocytes by regulating Nav1.7,thereby mitigating chondrocyte degeneration in KOA mice.


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