1.Expression and clinical significance of FAT1 gene in pancreatic adenocarcinoma
Xinyuan LIU ; Ying YANG ; Chaodan YANG ; Zhengxiao MA ; Conghui WU ; Chen XU ; Rui ZHU ; Pan LIU ; Lisha YING ; Wenjuan YIN ; Dan SU
Chinese Journal of Oncology 2024;46(11):1029-1037
Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P<0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P<0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P<0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P<0.001; ρ=0.28, P<0.001; ρ=0.32, P<0.001; ρ=0.21, P=0.004; ρ=0.32, P<0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P<0.001; r=0.231, P=0.002; r=0.258, P<0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P<0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.
2.Expression and clinical significance of FAT1 gene in pancreatic adenocarcinoma
Xinyuan LIU ; Ying YANG ; Chaodan YANG ; Zhengxiao MA ; Conghui WU ; Chen XU ; Rui ZHU ; Pan LIU ; Lisha YING ; Wenjuan YIN ; Dan SU
Chinese Journal of Oncology 2024;46(11):1029-1037
Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P<0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P<0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P<0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P<0.001; ρ=0.28, P<0.001; ρ=0.32, P<0.001; ρ=0.21, P=0.004; ρ=0.32, P<0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P<0.001; r=0.231, P=0.002; r=0.258, P<0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P<0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.
3.Research on the deep learning model based on the combination of intratumoral and peritumoral dynamic contrast-enhanced MRI for predicting axillary lymph node metastasis in breast cancer
Yijun GUO ; Rui YIN ; Junqi HAN ; Zhaoxiang DOU ; Jingjing CHEN ; Peifang LIU ; Hong LU ; Wenjuan MA
Journal of Practical Radiology 2024;40(6):907-912
Objective To explore the value of deep learning models in predicting axillary lymph node(ALN)metastasis of breast cancer based on intratumoral and peritumoral dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI).Methods A retrospective analysis was conducted on cases from Tianjin Medical University Cancer Hospital and Laoshan Branch of Affiliated Hospital of Qingdao University,involving a total of 850 lesions in 850 patients.The region of interest within the tumor was delineated at the largest area of the lesion on the first enhancement images and automatically expanded by 3 mm and 6 mm in a conformal fashion.Deep learning prediction models based on ResNet50 were developed via intratumoral,peritumoral,and intratumoral combined peritumoral models,respectively,and a comprehensive prediction model was developed by integrating semantic features of imaging reports.Cases from Tianjin Medical University Cancer Hospital were randomly divided into training and test cohorts in a 7∶3 ratio,while cases from Laoshan Branch of Affiliated Hospital of Qingdao University served as the external validation cohort.The area under the curve(AUC),accuracy,sensitivity,specificity,F1-score,and Brier-score were calculated,respectively.Results The model incorporating intratumoral,peritumoral(3 mm),and semantic features demonstrated the highest performance,with AUC of 0.801[95%confidence interval(CI)0.765-0.845],0.781(95%CI 0.745-0.817),and 0.752(95%CI 0.700-0.793)in the training cohort,test cohort,and external validation cohort,respectively,and there was no significant difference in AUC between combined model and intratumoral/peritumoral model,respectively,but it demonstrated the higher sensitivity and F1-score,and the lower Brier-score.Conclusion Incorporating peritumoral images into the conventional model based on intratumoral images enhanced the predictive ability of ALN metastasis in breast cancer.
4.Macrophage LMO7 deficiency facilitates inflammatory injury via metabolic-epigenetic reprogramming.
Shixin DUAN ; Xinyi LOU ; Shiyi CHEN ; Hongchao JIANG ; Dongxin CHEN ; Rui YIN ; Mengkai LI ; Yuseng GOU ; Wenjuan ZHAO ; Lei SUN ; Feng QIAN
Acta Pharmaceutica Sinica B 2023;13(12):4785-4800
Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.
5.Evidence summary of structured skin care for incontinence-associated dermatitis in adult inpatients
Wenjuan LI ; Haibo WANG ; Liang WANG ; Guandong WANG ; Xuehua ZHANG ; Yong BIN ; Yin CHEN
Chinese Journal of Modern Nursing 2022;28(14):1884-1890
Objective:To evaluate and summarize evidence related to structured skin care for incontinence-associated dermatitis (IAD) in adult inpatients, so as to provide a reference for clinical nursing decision-making.Methods:Clinical decisions, guidelines, evidence summaries, systematic reviews, expert consensus related to structured skin care for IAD in adult inpatients were retrieved by computer in British Medical Journal Best Practice, UpToDate, Joanna Briggs Institute Evidence-Based Health Care Centre in Australia, Canadian Registered Nurses Association of Ontario, Guidelines International Network, National Guideline Centre, National Institute for Health and Care Excellence, Medlive, the Cochrane Library, PubMed, Web of Science, CINAHL, Embase, WanFang Data, VIP, China National Knowledge Infrastructure, China Biomedical Literature Database. The retrieval time limit was from the establishment of the database to April 30, 2021. Two investigators independently assessed the quality of the included evidence and the level of recommendation.Results:A total of 14 articles were included, involving 2 clinical decisions, 1 practice guideline, 6 evidence summaries, 2 systematic reviews, and 3 expert consensus. A total of 29 best evidence was compiled from 4 aspects of structured skin care assessment, cleansing, moisturizing and isolation.Conclusions:Medical and nursing staff should integrate evidence with clinical scenarios and patient preferences to make optimal clinical decisions on structured skin care and improve the quality of care for adult inpatients with IAD.
6.Advances in applicaiton of platelets with cold storage at 4℃ and its storage lesion
Wenjuan LI ; Rui HE ; Yonghua YIN ; Zhong LIU
Chinese Journal of Blood Transfusion 2021;34(8):926-930
Platelet transfusion is one of the important therapeutic methods for clinical prevention of bleeding and hemostasis. At present, agitated storage at (22±2)℃used for platelets leads to risk of bacterial growth, which limits platelet shelf life and safety in transfusion. Cold storage at 4 ℃ can significantly promote the abovementioned drawbacks and present a better hemostatic effect. Platelets storage lesion(PSL) due to the cold storage, however, may lead to platelet activation following transfusion, thus reducing the effective survival rate in vivo. This paper reviews the research advances in PSL and the application of platelets stored at 4 ℃.
7.Clinicopathological characteristics and prognosis of IgA nephropathy patients with gross hematuria
Xiaojuan GU ; Huifang WANG ; Wenjuan YIN ; Xueling XU ; Yingying LIU ; Dandan GUO ; Xuemei LIU
Chinese Journal of General Practitioners 2021;20(5):581-586
Objective:To investigate the clinicopathological features and prognosis of IgA nephropathy (IgAN) patients with gross hematuria.Methods:The clinical and pathological data of 490 primary IgAN patients admitted in the Affiliated Hospital of Qingdao University from January 2010 to June 2019 were analyzed. Patients were divided into gross hematuria group and non-gross hematuria group. The clinical and pathological features and prognosis were compared between the two groups. All patients were diagnosed by kidney biopsy, and followed up until June 30, 2020. Kaplan-Meier survival curve was used to examine the renal survival,and Cox regression model was used to analyze the risk factors affecting renal survival in two groups.Results:Among 490 patients there were 111 patients (22.7%) in the gross hematuria group and 379 patients (77.3%) in the non-gross hematuria group. Age, hypertension, 24-h urine protein, serum creatinine, blood uric acid, blood triglycerides, total blood cholesterol level, mesangial cell hyperplasia (M1), the proportion of renal tubular atrophy or renal interstitial fibrosis (T1/2) in gross hematuria group were lower than those in non-gross hematuria group ( P<0.05), while the estimated glomerular filtration rate (eGFR) in gross hematuria group was higher than those in non-gross hematuria group ( P<0.05). Four hundred and twenty six patients (86.9%) were followed up for at least 6 months, including 93 patients in gross hematuria group and 333 patients in non-gross hematuria group. There was no statistically significant difference in treatment method between the two groups ( P>0.05). The incidence of end-point events in non-gross hematuria group was higher than that in gross hematuria group [18.6%(62/333) vs. 6.5%(6/93), χ2=8.023, P<0.05]. Kaplan-Meier survival analysis showed that the cumulative renal survival rate of the gross hematuria group was higher than that of the non gross hematuria group (χ2=11.44, P<0.001). Multivariate Cox regression analysis showed that urine protein>1 g/24 h, eGFR<60 ml·min -1·(1.73 m 2) -1, hypertension, hyperuricemia and the elevated serum IgA/C3 were risk factors for renal survival [ HR(95% CI)=3.457(1.137-10.514),2.736(1.073-6.977),2.720(1.144-6.465),2.789(1.102-7.060),1.070(1.009-1.135), all P<0.05]. Conclusions:IgAN patients with gross hematuria has less severe kidney damage and higher cumulative renal survival rate than non-gross hematuria patients. Urinary protein>1.0 g/d, hypertension, hyperuricemia and the elevated serum IgA/C3 are risk factors for adverse end-point events, to which timely attention and corresponding treatment should be given.
8.Dysregulated Dermal Mesenchymal Stem Cell Proliferation and Differentiation Interfered by Glucose Metabolism in Psoriasis
Xincheng ZHAO ; Jianxiao XING ; Junqin LI ; Ruixia HOU ; Xuping NIU ; Ruifeng LIU ; Juanjuan JIAO ; Xiaohong YANG ; Juan LI ; Jiannan LIANG ; Ling ZHOU ; Qiang WANG ; Wenjuan CHANG ; Guohua YIN ; Xinhua LI ; Kaiming ZHANG
International Journal of Stem Cells 2021;14(1):85-93
Background and Objectives:
Psoriasis is a chronic inflammatory skin disease, which the mechanisms behind its initiation and development are related to many factors. DMSCs (dermal mesenchymal stem cells) represent an important member of the skin microenvironment and play an important role in the surrounding environment and in neighbouring cells, but they are also affected by the microenvironment. We studied the glucose metabolism of DMSCs in psoriasis patients and a control group to reveal the relationship among glucose metabolism, cell proliferation activity,and VEC (vascular endothelial cell) differentiation in vitro, we demonstrated the biological activity and molecular mechanisms of DMSCs in psoriasis.
Methods:
and Results: We found that the OCR of DMSCs in psoriatic lesions was higher than that in the control group, and mRNA of GLUT1 and HK2 were up-regulated compared with the control group. The proliferative activity of DMSCs in psoriasis was reduced at an early stage, and mRNA involved in proliferation, JUNB and FOS were expressed at lower levels than those in the control group. The number of blood vessels in psoriatic lesions was significantly higher than that in the control group (p<0.05), which the mRNA of VEC differentiation, CXCL12, CXCR7, HEYL and RGS5 tended to be increased in psoriatic lesions compared to the control group, in addition to Notch3.
Conclusions
We speculated that DMSCs affected local psoriatic blood vessels through glucose metabolism, and the differentiation of VECs, which resulted in the pathophysiological process of psoriasis.
9.Efficacy analysis of 595 nm pulsed dye laser treatment for superficial hemangioma on different sites in infants
Siding LU ; Wenjuan SHEN ; Mingde LIAO ; Jia LIAO ; Zhao QIN ; Chunyan LI ; Guoqian YIN
Chinese Journal of Plastic Surgery 2021;37(12):1320-1327
Objective:To investigate the clinical effect of 595 nm pulsed dye laser treatment for superficial hemangiomas on different sites of infants(≤3 years old) .Methods:From January 2018 to January 2020, we retrospectively analyzed the data of infants with superficial hemangioma in our hospital. They were treated with 595 nm pulsed dye laser. The energy and frequency of laser treatment, the effects and adverse reactions were recorded. t-test, SNK- q test and Chi-square test were used to analyze the data. Results:A total of 437 infants were enrolled, including 168 male and 269 female. The ages ranged from 0 to 36 months. They were divided into different lesion sites as head (34 cases) , forehead (37 cases) , cheek (61 cases) , periocular (30 cases) , nose (21 cases) , lip (12 cases) , perioral (10 cases) , ear (16 cases) , neck (26 cases) , chest (36 cases) , abdomen (24 cases) , back (21 cases) , buttocks (12 cases) , perineum (14 cases) , upper arm and forearm (30 cases) , hand (25 cases) , thigh (18 cases) , and foot (10 cases) . The average treatment energy of each sites was 8.0 J/cm 2 , with no significant difference( P>0.05) . The average number of treatments on the head, forehead, cheek, periocular, nasal, lip, perioral and foot was higher than that on other sites, showing a statistical significance ( P<0.05) ; among them, the nasal and perioral parts had most treatments. The total effective rate was 96.57%(422/437). The complications happened in 35 cases(8.01%), including hypopigmentation(22 cases), hyperpigmentation(5 cases), atrophic scar (8 cases). Conclusions:595 nm pulsed dye laser has a good therapeutic effect on infantile superifcial hemangioma with low adverse effect. Hemangioma on different sites requires different times of treatment.
10.Efficacy analysis of 595 nm pulsed dye laser treatment for superficial hemangioma on different sites in infants
Siding LU ; Wenjuan SHEN ; Mingde LIAO ; Jia LIAO ; Zhao QIN ; Chunyan LI ; Guoqian YIN
Chinese Journal of Plastic Surgery 2021;37(12):1320-1327
Objective:To investigate the clinical effect of 595 nm pulsed dye laser treatment for superficial hemangiomas on different sites of infants(≤3 years old) .Methods:From January 2018 to January 2020, we retrospectively analyzed the data of infants with superficial hemangioma in our hospital. They were treated with 595 nm pulsed dye laser. The energy and frequency of laser treatment, the effects and adverse reactions were recorded. t-test, SNK- q test and Chi-square test were used to analyze the data. Results:A total of 437 infants were enrolled, including 168 male and 269 female. The ages ranged from 0 to 36 months. They were divided into different lesion sites as head (34 cases) , forehead (37 cases) , cheek (61 cases) , periocular (30 cases) , nose (21 cases) , lip (12 cases) , perioral (10 cases) , ear (16 cases) , neck (26 cases) , chest (36 cases) , abdomen (24 cases) , back (21 cases) , buttocks (12 cases) , perineum (14 cases) , upper arm and forearm (30 cases) , hand (25 cases) , thigh (18 cases) , and foot (10 cases) . The average treatment energy of each sites was 8.0 J/cm 2 , with no significant difference( P>0.05) . The average number of treatments on the head, forehead, cheek, periocular, nasal, lip, perioral and foot was higher than that on other sites, showing a statistical significance ( P<0.05) ; among them, the nasal and perioral parts had most treatments. The total effective rate was 96.57%(422/437). The complications happened in 35 cases(8.01%), including hypopigmentation(22 cases), hyperpigmentation(5 cases), atrophic scar (8 cases). Conclusions:595 nm pulsed dye laser has a good therapeutic effect on infantile superifcial hemangioma with low adverse effect. Hemangioma on different sites requires different times of treatment.

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