1.Role of chloride ions in the prognosis of patients with decompensated cirrhosis
Tian MENG ; Ouyang JING ; Chang HONG ; Yang JIN ; Liu MIN ; Yuping WANG ; Zhaofeng CHEN
Journal of Chongqing Medical University 2025;50(3):367-375
Objective:To investigate the prognostic value of serum chloride ion concentration in critically ill or clinically stable pa-tients with decompensated cirrhosis.Methods:A retrospective study was conducted among the patients with decompensated cirrhosis who attended the intensive care unit(ICU)and Department of Gastroenterology,The First Hospital of Lanzhou University,from Janu-ary 2017 to January 2022,and the patients were divided into ICU cohort and Gastroenterology cohort.The outcome event for the ICU cohort was in-hospital death.A logistic regression analysis was used to investigate the association between serum chloride levels and ICU mortality rate;the receiver operating characteristic(ROC)curve was plotted and the area under the ROC curve(AUC)was calcu-lated to assess the value of blood chloride level in predicting ICU mortality rate.The patients in the Gastroenterology cohort were fol-lowed up with the outcome event of all-cause mortality rate,and the Cox regression analysis and the Kaplan-Meier analysis were used to investigate the value of blood chloride level in predicting mortality rate.Results:In the ICU cohort,serum chloride ion was signifi-cantly associated with in-hospital mortality in the ICU(odds ratio=0.934,95%CI=0.871-0.993,P=0.035),and blood chlorine had an AUC of 0.687 in predicting in-hospital mortality in the ICU.In the Gastroenterology cohort,serum chloride ion concentration was sig-nificantly associated with mortality rate in the subgroup with a Child-Pugh score of<10(hazard ratio=0.906,95%CI=0.822-0.997,P=0.043),and hypochloremia was associated with a lower survival rate.Conclusion:Hypochloremia is associated with the increase in mortality rate in patients with decompensated cirrhosis.
2.Effect of dandelion polysaccharide on inflammatory response and expression of S100 calcium binding protein A8/A9 in lung and intestinal injuries in rats with multiple organ dysfunction syndrome
Han LI ; Wenlong YU ; Zhaofeng YANG ; Yan LIU ; Qian ZHANG ; Jianhui WANG ; Liyan ZHU ; Jiehui ZUO ; Xiuhong YANG
Journal of Chongqing Medical University 2025;50(10):1399-1407
Objective:To investigate the effect of dandelion polysaccharide(DP)on inflammatory response and the protein expression of S100 calcium binding protein A8/A9(S100A8/A9)in lung tissue and small intestinal tissue of rats with multiple organ dysfunction syndrome(MODS).Methods:The two-hit method of hemorrhagic shock and intraperitoneally injected lipopolysaccharide was used to establish a rat model of MODS,and the rats were divided into sham-operation group,model group,low-dose DP group,and high-dose DP group.The organ coefficient and wet/dry weight ratio of the lung and the small intestine were observed for each group of rats;HE staining was used to observe the pathomorphological changes of lung tissue and small intestinal tissue;immunohistochemical staining was used to measure the expression of interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-10(IL-10)in lung tissue and small intestinal tissue;Western blot was used to measure the protein expression level of S100A8/A9 in lung tissue and small intestinal tissue.Results:Compared with the sham-operation group,the model group had significant increases in the organ coefficient of the lung(5.849±0.824),the wet/dry weight ratio of the lung(6.556±0.631),the wet/dry weight ratio of the small intestine(6.356±0.535),and the wet weight/length ratio of the small intestine(73.950±5.569).HE staining showed that that the model group had massive in-flammatory cell infiltration in alveolar space and pulmonary interstitium,thickened alveolar wall,and disintegration and fragmentation of the villi of the small intestine,with inflammatory cell infiltration and proliferation of segmental aggregated lymphoid follicles.In the model group,S100A8/A9 was mainly expressed in neutrophils and macrophages,and there were increases in the expression of S100A8/A9,IL-1β,and IL-6 and a reduction in the expression of IL-10 in the lung tissue and small intestinal tissue of rats.After treatment with high-dose DP,there were reductions in the organ coefficient of the lung(4.297±0.462),the wet/dry weight ratio of the lung(5.313±0.495),the wet/dry weight ratio of the small intestine(5.398±0.388),and the wet weight/length ratio of the small intestine(59.417±2.891).The high-dose group also had alleviation of pathological injury in the small intestine,with reductions in the expres-sion of S100A8/A9,IL-1β,and IL-6 and an increase in the expression of IL-10 in lung tissue and small intestinal tissue.Conclusion:DP may alleviate inflammatory response in lung and small intestinal injuries of rats with MODS by inhibiting the expression of S100A8/A9.
3.Association study of pediatric obstructive sleep apnea hypopnea syndrome and otitis media with effusion based on clinical prediction model and Mendelian randomization
Yahui ZHAO ; Jianzhou GUO ; Wei CHANG ; Zhaofeng QIU ; Yu LIU
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(6):381-385
OBJECTIVE To explore the correlation between childhood obstructive sleep apnea hypopnea syndrome and otitis media with effusion,to provide evidence-based basis for clinical diagnosis and treatment.METHODS A total of 985 children were diagnosed in the Department of Otolaryngology,Heping Hospital Affiliated to Changzhi Medical College from September 2019 to March 2025.Combined or no OME patients for multivariate logistics regression analysis and construct related risk prediction model,obtain data of OSAHS(exposure factors)and OME(outcome)from the public database of genome-wide association studies(GWAS),two-sample Mendelian randomization(MR)analysis.RESULTS The risk prediction model for OME in children with OSAHS,Hosmer-Lemeshow goodness of fit test(χ2=12.541,P=0.157),C index of 0.749,Calibration calibration curve fitting,and correlation between children OSHAS and OME.Furthermore,the MR analysis using inverse variance weighting observed a positive causal relationship between OSAHS and OME in children(OR=1.05,95%CI=0.999-1.051,P=0.005).MR Egger test results(Q=42.358,P=0.716)and IVW(Q=43.271,P=0.759)showed no heterogeneity in the analysis,MR Egger intercept(intercept=-0.004,P=0.921)showed no horizontal pleiotropy,and the MR analysis results were stable.CONCLUSION There is a correlation between pediatric OSAHS and OME,and it increases the risk of OME.
4.Causal relationship between circulating inflammatory factors and sensorineural hearing loss:A two-way Mendelian randomization study
Zhaofeng QIU ; Wei CHANG ; Jianzhou GUO ; Yu LIU ; Yahui ZHAO
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(11):717-721
OBJECTIVE To explore the causal relationship of circulating cytokines and sensorineural deafness by Mendelian randomization.METHODS Large-scale genome-wide association studies(GWAS)data sets based on UK Biobank were used to identify single nucleotide polymorphisms(SNP)associated with exposure and outcome.The SNP(F>10)significantly associated with exposure data(P<5e-6)and strongly associated with exposure in the F statistic was selected as the instrumental variable for a two-sample Mendelian randomization analysis.The causal effect was estimated using MR-Egger,regression and inverse variance weighting(IVW).Sensitivity analysis was performed to assess the robustness of the results.RESULTS This study confirmed that VEGF(OR=1.04,95%CI:1.01-1.07,P=0.00),SDF-1α(OR=1.10,95%CI:1.02-1.18,P=0.01)and IL-13(OR=1.04,95%CI:1.01-1.06,P=0.01),IL-10(OR=1.06,95%CI:1.02-1.11,P=0.01),IL-7(OR=1.05,95%CI:1.01-1.08,P=0.00)increased the risk of sensorineural deafness.The backward analysis did not find that sensorineural deafness significantly affected the levels of these cytokines.No significant heterogeneity or horizontal pleiotropy was observed among the instrumental variables.CONCLUSION This study reveals a positive correlation between elevated levels of VEGF,SDF-1α,IL-13,IL-10,and IL-7 with sensorineural hearing loss,providing novel targets for further development of biomarkers for the prediction,treatment,and prevention of sensorineural hearing loss.
5.Effect and mechanism of ammonium pyrrolidine dithiocarbamate on neuroinflammation in rats with traumatic brain injury
Jiafa YANG ; Zhaofeng LU ; Yaqiong WANG ; Ruoyu LU ; Hairong LI ; Mengjia LIU
Journal of Xinxiang Medical College 2024;41(7):631-639
Objective To investigate the effect and mechanism of ammonium pyrrolidine dithiocarbamate(PDTC)on neuroinflammatory injury in the penumbra of traumatic brain injury(TBI)in rats.Methods Sixty Sprague Dawley rats were divided into the PDTC group,TBI group,sham operation group and control group according to the random number table method,with 15 rats in each group.Rats in the PDTC group were intraperitoneally injected with PDTC(100 mg·kg-1)at 15 minutes before surgery;while the rats in the TBI group,sham operation group,and control group were intraperitoneally injected with the same volume of double distilled water.After the cranial window of rats in the TBI group and PDTC group was created,a 2.5 g steel rod with an inner diameter of 6.0 mm was dropped freely from a height of 75 cm through a transparent polyvinyl chloride tube with an inner diameter of 7.0 mm to impact the dura mater and induce right parietal lobe contusion and laceration to establish the TBI model;rats in the sham operation group were sealed with bone wax after the cranial window creation,without any impact applied;rats in the control group were raised under normal conditions.The modified neurological severity score(mNSS)was used to evaluate the degree of neurobehavioral damage in rats in each group at 1,4 and 7 days after modeling.At 2 days after modeling,5 rats in each group were decapitated,and brain tissues were taken for hematoxylin & eosin(HE)staining,and morphological changes of the brain tissues were observed under an optical microscope.The expressions of β-amyloid precursor protein(β-APP)and glial fibrillary acidic protein(GFAP)in the brain tissues of rats in each group were detected by immunohistochemical staining.At 24 hours after modeling,5 rats in each group were decapitated,and the right injured penumbra tissues were obtained;the expressions of nuclear transcription factor-κB(NF-κB)P65,phosphorylated NF-κB P65,inhibitor of NF-κB(IκB),phosphorylated IKB,NOD-like receptor protein 3(NLRP3)and caspase-1 protein in the right injured penumbra tissue of rats in each group were detected by Western blot,and the expressions of NF-κB P65,IκB,NLRP3 and caspase-1 mRNA in the right injured penumbra tissue of rats in each group were determined by real-time quantitative polymerase chain reaction.Results At 1,4,and 7 days after modeling,the mNSS scores of rats in the TBI group were signifi-cantly higher than those in the PDTC group,control group and sham operation group.The mNSS scores of rats in the PDTC group were significantly higher than those in the control group and sham operation group(P<0.05);there was no statistically significant difference in mNSS scores between the sham operation group and the control group(P>0.05).The neurons and neurogliocyte of rats in the control group and the sham operation group exhibited normal morphology,without swelling and wide-ning of intercellular space.Diffuse hemorrhagic changes were observed in the brain tissues of rats in the TBI group,with different morphologies of neuronal cell body,unclear cell membrane and cytoplasm,pyknosis of cell nuclei,often triangular shape,disappearance of normal structure and nucleoli,and diffuse white blood cells and red blood cells filling the field of vision.The lesion surrounding area of rats in the PDTC group showed ischemic changes,with mild shrinkage of neuronal volume,a uniform light red color,karyopyknosis,nuclear-cytoplasmic dissociation,disappearance of normal structure and nucleoli,and localization of neuroinflammation.There was no significant expression of β-APP and GFAP in the cerebral cortex of rats in the control group and the sham operation group,while the accumulation of β-APP and GFAP in neuronal serosae and/or axons was observed in the brain tissues of rats in the TBI group and the PDTC group.Compared with the TBI group,a decrease in the number and the expression intensity of β-APP and GFAP-positive stained neuronal cells in the cerebral cortex of rats was observed in the PDTC group.The relative expression of NF-κB P65 protein in the brain tissues of rats in the sham operation group,TBI group and PDTC group was significantly higher than that in the control group,and the relative expression of NF-κB P65 protein in the brain tissues of rats in the PDTC group was significantly higher than that in the TBI group(P<0.05).The relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the PDTC group and the sham operation group was significantly lower than that in the control group,the relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the TBI group was significantly higher than that in the control group and the sham operation group,and the relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the PDTC group was significantly lower than that in both TBI group and sham operation group(P<0.05).There was no significant difference in the relative expression of IκB protein in the brain tissues of rats between the sham operation group and the control group(P>0.05);the relative expression of IκB protein in the brain tissues of rats in the TBI group was significantly higher than that in the control group,and the relative expression of IκB protein in the brain tissues of rats in the PDTC group was significantly lower than that in the control group,sham operation group,and TBI group(P<0.05).The relative expression of phosphorylated IκB protein in the brain tissues of rats in the TBI group was significantly lower than that in the control group and the sham operation group,and the relative expression of phosphorylated IκB protein in the brain tissues of rats in the PDTC group was significantly higher than that in the TBI group(P<0.05).The relative expression of NLRP3 protein in the brain tissues of rats in the sham opera-tion group was significantly higher than that in the control group,the relative expression of NLRP3 protein in the brain tissues of rats in the TBI group and the PDTC group was significantly lower than that in the sham operation group and the control group,and the relative expression of NLRP3 protein in the brain tissues of rats in the TBI group was significantly lower than that in the PDTC group(P<0.05).The relative expression of caspase-1 protein in the brain tissues of rats in the sham opera-tion group,PDTC group,and TBI group was significantly higher than that in the control group,and the relative expression of caspase-1 protein in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P<0.05).The relative expression of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group,TBI group,and sham operation group was significantly higher than that in the control group,the relative expression of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expres-sion of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P<0.05).The relative expression of IκB mRNA in the brain tissues of rats in the PDTC group and TBI group were signifi-cantly higher than that in the control group,and the expression of IκB mRNA in the brain tissues of rats in the sham operation group was significantly lower than that in the control group(P<0.05).The relative expression of IκB mRNA in the brain tis-sues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expression of IκB mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P<0.05).The relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the control group,the relative expression of NLRP3 mRNA in the brain tissues of rats in the sham operation group was significantly lower than that in the control group,the relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P<0.05).The relative expression of caspase-1 mRNA in the brain tissues of rats in the sham operation group,TBI group,and PDTC group was significantly lower than that in the control group,the relative expression of caspase-1 mRNA in the brain tissues of rats in the TBI group and PDTC group was significantly higher than that in the sham operation group(P<0.05).Conclusion PDTC can effectively improve neural functional deficit score and reduce neuroinflammatory injury in TBI rats,the mechanism of which may be related to regulating mRNA and protein expression of NF-κB/NLRP3 axis-related inflammatory injury indicators and regulating downstream inflammatory factors.
6.Correlation of ARK5 expression in peripheral blood circulating tumor cells with curative efficacy and prognosis for gemcitabine chemotherapy in pancreatic cancer patients
Zhaofeng GAO ; Wei GUO ; Xiaodan YANG ; Xiaorong LIU ; Lingyu HU ; Xiaoguang WANG
Chinese Journal of Pancreatology 2023;23(5):330-334
Objective:To detect the expression of ARK5 in peripheral blood circulating tumor cells (CTCs) from pancreatic cancer patients and explore its correlation with the efficacy and prognosis for gemcitabine chemotherapy.Methods:A total of 175 peripheral blood samples of pancreatic cancer patients who were treated in the Department of Hepatobiliary Surgery, Second Affiliated Hospital of Jiaxing University from January 2016 to June 2021 were collected. CTCs were enriched by nano-microfluidic chip technology. The expression of ARK5 in CTCs was detected by immunofluorescence. According to the expression of ARK5, the patients were divided into two groups: positive group and negative group. The differences on clinicopathological features, the efficacy of chemotherapy, median survival and progression-free survival time between the two groups were compared.Results:CTCs were enriched in 98 of 175 patients (55.6%), including 70 ARK5 positive and 28 ARK5 negative patients. There were no significant differences on clinical features between the two groups, and the two groups were comparable. In the 70 ARK5 positive patients, 64 patients (91.4%) were resistant to gemcitabine, while only 12 of the 28 ARK5 negative patients (42.8%) were resistant to gemcitabine. The incidence of gemcitabine resistance in ARK5 positive patients was significantly higher than that in ARK5 negative patients, and the difference was statistically significant ( P<0.001). The median survival time was 11.5 months in ARK5 positive group and 14 months in ARK5 negative expression group, and the progression-free survival time was 6 months in ARK5 positive expression group and 8 months in negative expression group. The survival time of ARK5 positive group was significantly shorter than that of ARK5 negative group, and the difference was statistically significant ( P<0.05). Conclusions:The pancreatic cancer patients with ARK5 positive CTCs have significantly higher incidence of gemcitabine resistance and shorter survival time than those with ARK5 negative CTCs. Detection of ARK5 expression in CTCs may be a new method to judge chemotherapy efficacy and prognosis for pancreatic cancer patients.
7. Regulation mechanism of post-translational modification of farnesoid X receptor
Zhaofeng LIU ; Ling LI ; Shufang NA ; Qifa YE ; Jiang YUE ; Qifa YE
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(11):1292-1298
Farnesoid X receptor (FXR) is a nuclear receptor activated by bile acid that is involved in regulating gene expression related to bile acid, fat, glucose, and amino acid metabolism. The activity of FXR is regulated by a variety of post-translational modifications. Common post-translational modifications of FXR include O-GlcNAcylation, phosphorylation, acetylation, sumoylation, methylation, etc. These post-translational modifications may affect FXR binding of DNA and ligand, heterodimerization, and subcellular localization, and may specifically regulate downstream gene transcription and expression. Different post-translational modifications can lead to changes in FXR stability and biological function, which are closely related to the occurrence of diseases. This paper aims to review the post-translational modification of FXR in the past five years and the mechanisms involved in disease regulation, to explore the effects of post-translational modification on the physiological function of FXR and to provide a theoretical basis for mechanism research targeting FXR.
8.Digital design and 3D-printed customized flanged cups in hip revision with severe acetabular bone defects
Yujian DING ; Dehong FENG ; Ling WANG ; Yu GUO ; Yi LIU ; Yiyi ZHOU ; Sutong GUO ; Zhengying QIAN ; Kuixue XU ; Zhaofeng ZHANG
Chinese Journal of Orthopaedics 2023;43(2):97-103
Objective:To investigate the effect of 3D-printed customized flanged cup in hip revision with severe acetabular bone defects.Methods:Since February 2017, 10 cases of 3D-printed customized flanged cups were used in hip revision with severe acetabular bone defects, including 2 cases of Paprosky type IIIA and 8 cases of Paprosky type IIIB. There were 5 males and 5 females, mean age 73.6±8.1 yrs (range, 62-87 yrs), 5 left and 5 right cases. The preoperative thin-layer CT scan was preformed to reverse reconstruct digital pelvis. Five cases of one-piece flanged cups and 5 cases of decomposed flanged cups, including 3 cases of composite one-piece cups were designed by computer. The surgery was performed strictly according to the plan.Postoperative follow-up was performed to evaluate the Harris score. Operation time,intraoperative bleeding and other complications such as vascular and nerve injury, postoperative infection, and dislocation were counted. Pelvic X-ray was used to assess the height and horizontal position of the center of rotation and the stability of the prosthesis.Results:The surgical procedure was successful, with an average operative time of 147.9±48.3 min (range, 96-212 min) and an average intraoperative bleeding of 730.4±262.6 ml (range, 500-1 300 ml). The mean time of final follow-up was 40.8±18.7 months (range, 16-70 months) after surgery. At the last follow-up, the average Harris score was 83.80±6.73, with 4 cases excellent, 5 cases good, and 1 case fair. The excellent and good rate was 90%. The last Harris score was significantly higher than that before operation 28.60±8.40 ( t=16.84, P<0.001). The height of affected hip joint rotation center decreased from 46.24±7.74 mm before operation to 15.54±2.54 mm after operation with significant difference ( t=14.61, P<0.001). It was slightly higher than the opposite side (13.81±1.48 mm), which had no significant difference ( t=1.83, P=0.100). The horizontal distance of affected hip joint rotation center increased from 33.79±5.27 mm before operation to 40.53±4.50 mm after operation with significant difference ( t=3.62, P=0.006). It had no significant difference ( t=1.28, P=0.232) compared with the opposite side (38.54±3.46 mm). All incisions were healed in one stage without infection, vascular or nerve injury. During the following-up, all prostheses were in satisfied position without loosening, dislocation or screw breaks. Conclusion:Digitally assisted 3D-printed flanged cups can be used in hip revision with severe acetabular bone defect. It can not only improve hip joint function, but also restore the acetabular rotation center and the prosthesis stability, which can achieve good early and mid-term effect.
9.Role of platelets in the development and progression of hepatocellular carcinoma
Xiao YU ; Guobing WU ; Aibin ZHANG ; Xiaolong CHENG ; Min LIU ; Zenan HU ; Ya ZHENG ; Yuping WANG ; Zhaofeng CHEN
Journal of Clinical Hepatology 2022;38(6):1426-1430
Hepatocellular carcinoma is one of the common causes of tumor-related death, and it has high morbidity and mortality rates in China. Recent studies have shown that platelets are closely associated with the development of hepatocellular carcinoma. Literature review shows that platelets not only participate in hemostasis, but also act on liver cells and tumor microenvironment, promote the formation of new blood vessels, and participate in the development and progression of hepatocellular carcinoma as a cell mediator through immune response and other pathways. In addition, platelets and their derivatives can be used as potential therapeutic targets for hepatocellular carcinoma. Therefore, antiplatelet therapy is expected to become a new adjuvant strategy for the treatment of hepatocellular carcinoma, which has important clinical significance.
10.Effect of sequential suture and adhesion on craniomaxillofacial skin contusion and laceration
Zhaofeng LU ; Yitong ZHU ; Yaqiong WANG ; Jiafa YANG ; Ruoyu LU ; Hairong LI ; Mengjia LIU
Chinese Journal of Medical Aesthetics and Cosmetology 2022;28(5):368-371
Objective:To investigate the effect of sequential suture and adhesion on craniomaxillofacial skin contusion and laceration.Methods:A total of 189 patients with craniomaxillofacial skin contusion and laceration (CMFSCL) were randomly divided into three groups: 66 cases in SSA group, 63 cases in CS group and 60 cases in TS group. Operation time, visual analogue scale (VAS), Vancouver scar scale (VSS) and adverse reactions incidence were compared and analyzed between the three groups. Effect and satisfactory scale were evaluated.Results:Operation time in SSA group (10.67±1.26) min was significantly less than that in CS (18.91±1.38) min and TS group (17.96±1.43) min ( P<0.05). VAS in SSA group 24 h post-operation (3.11±1.01) was significantly lower than that in CS and TS group ( P<0.05). VSS in SSA group 6 months post-operation (1.18±0.21) was significantly lower than that in CS (3.78±1.01) ( P<0.05) and TS group (5.98±1.06) ( P<0.01). Total effective rate of SSA group (96.5%) was significantly higher than that in CS (85.7%) ( P<0.05) and TS group (56.1%) ( P<0.01); total effective rate in CS group was significantly higher than that in TS group ( P<0.05). Infection and dehiscence rates in SSA group were lower than those in CS and TS group ( P<0.01). Satisfactory rate of SSA group (99%) was significantly higher than that of CS (89.1%) and TS group (71.3%) ( P<0.05); the satisfactory rate of CS group was significantly higher than that of TS group ( P<0.05). Conclusions:Sequential suture and adhesion technique is simple and effective for craniomaxillofacial skin contusion and laceration, which is worthy of clinical promotion.

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