1.Effect of ultrasound-guided foraminal electroacupuncture on spinal cord injury based on the Wnt/β-catenin signaling pathway.
Weixian WU ; Bin CHEN ; Jing LIU ; Li WANG ; Feizhen CHEN ; Yanling WU
Chinese Acupuncture & Moxibustion 2025;45(10):1442-1449
OBJECTIVE:
To observe the effects of ultrasound-guided foraminal electroacupuncture on neuronal apoptosis and motor function in rats with spinal cord injury (SCI), and to explore the potential underlying mechanisms.
METHODS:
Thirty-six SPF-grade Sprague-Dawley rats were randomly assigned to a sham operation group, a model group, and an ultrasound-guilded electroacupuncture group (electroacupuncture group), with 12 rats in each group. In the sham operation group, the spinal cord was exposed and then the incision was sutured without contusion. In the other two groups, SCI models were established using a modified Allen's impact method. On days 1, 3, 7, and 14 after modeling, the electroacupuncture group received electroacupuncture intervention at the T9/T10 and T10/T11 intervertebral foramen under ultrasound guidance, avoiding spinal cord injury. Stimulation parameters were dense-disperse wave at 2 Hz/100 Hz and 1-2 mA for each session. Following interventions on days 1, 3, 7, and 14, the Basso-Beattie-Bresnahan (BBB) score was assessed; the inclined plane test was used to assess hindlimb grip strength in rats. After the intervention, HE staining was used to observe spinal cord morphology; TUNEL staining was used to detect neuronal apoptosis; ELISA was used to measure the serum levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α); Western blot was used to analyze the protein expression of Wnt-4, β-catenin, c-Myc, Bax, Bcl-2, and NeuN in spinal tissue; quantitative real-time PCR was used to detect the mRNA expression of Wnt-4, β-catenin, c-Myc, Bax, Bcl-2, and NeuN.
RESULTS:
Compared with the sham operation group, the model group showed significantly reduced BBB scores (P<0.05), and reduced inclined plane angles (P<0.05) at all time points. Compared with the model group, the electroacupuncture group exhibited increased BBB scores on days 3, 7, and 14 (P<0.05), and higher inclined plane angles on days 1, 3, 7, and 14 (P<0.05). Compared with the sham operation group, the model group showed disorganized spinal cord structure with increased inflammatory cells and necrotic neurons, higher number of apoptotic neurons in spinal tissue (P<0.05), elevated serum IL-6, IL-1β, and TNF-α levels (P<0.05), increased protein and mRNA expression of Wnt-4, β-catenin, c-Myc, and Bax (P<0.05), and decreased protein and mRNA expression of Bcl-2 and NeuN in spinal tissue (P<0.05). Compared with the model group, the electroacupuncture group had fewer inflammatory cells and apoptotic neurons in spinal tissue (P<0.05), reduced serum IL-6, IL-1β, and TNF-α levels (P<0.05), increased protein and mRNA expression of Wnt-4, β-catenin, Bcl-2, and NeuN (P<0.05), and decreased protein and mRNA expression of c-Myc and Bax in spinal tissue (P<0.05).
CONCLUSION
Ultrasound-guided foraminal electroacupuncture could improve motor function in rats with SCI, potentially by regulating the expression of molecules related to the Wnt-4/β-catenin signaling pathway to inhibit neuronal apoptosis and inflammatory responses.
Animals
;
Electroacupuncture/methods*
;
Spinal Cord Injuries/physiopathology*
;
Rats, Sprague-Dawley
;
Rats
;
Wnt Signaling Pathway
;
Male
;
Humans
;
Female
;
beta Catenin/metabolism*
;
Apoptosis
;
Ultrasonography
;
Tumor Necrosis Factor-alpha/genetics*
;
Spinal Cord/metabolism*
2.Optimization of the clinical drug list of DRG based on data mining technology
Qinsu YUN ; Weixian ZHOU ; Hui XU ; Meng LIU ; Rong CHEN
China Pharmacy 2024;35(13):1558-1563
OBJECTIVE To optimize the clinical drug list of diagnosis-related group (DRG), reduce the drug cost of patients, and increase the DRG settlement rate. METHODS By selecting BR23 disease group in the department of neurology of a hospital as the research object, data mining technology was used to explore the medication rule of the disease group, and the key monitored drugs were scored by comprehensive evaluation of drugs, thus optimizing the clinical drug list of disease groups. The hospitalization information of patients enrolled in the disease group in December 2022 was selected as the pre-optimization data, and the hospitalization information of patients enrolled in the disease group in September 2023 was selected as the post-optimization data. The implementation effect of the optimized list was evaluated by comparing the medical quality and drug cost data between the two groups. RESULTS After optimizing the clinical drug list, the settlement rate of this disease group increased from 84.36% before optimization to 104.70%; there was significant reduction in hospitalization drug cost and total hospitalization cost (P< 0.05); the consumption of key monitored drugs significantly decreased. CONCLUSIONS Data mining technology helps explore the clinical medication rules of disease groups, which can be used by pharmacists to improve the settlement rate of DRG through effective pharmaceutical intervention.
3.Phylogenetic and antigenic analysis on hemagglutinin gene of influenza B virus (Victoria) in 2023-2024 surveillance season in Beijing
Guilan LU ; Jiachen ZHAO ; Weixian SHI ; Li ZHANG ; Yimeng LIU ; Zhaomin FENG ; Ying SUN ; Daitao ZHANG ; Xiaomin PENG
Chinese Journal of Experimental and Clinical Virology 2024;38(4):415-421
Objective:To disclose phylogenetic and antigenic characteristics of hemagglutinin (HA) gene of influenza B virus (Victoria) (BV) in the 2023-2024 influenza surveillance season in Beijing, and understand the matching with influenza vaccine component strain.Methods:Pharyngeal swab specimens from influenza like-illness (ILI) in the 2023-2024 influenza surveillance season were collected from surveillance network labs in Beijing and BV strains were isolated through MDCK or chicken embryo culture. After extracting nucleic acid, HA gene was amplified and sequenced. The nucleotide and amino acid sequence identity were conducted and the maximum likelihood method in Mega 5.0 software was used to construct the phylogenetic tree of HA gene. N-glycosylation sites of HA were performed online. Furthermore, three-dimensional structure of HA was available from SWISS-MODEL homologous modeling. Hemagglutination inhibition (HI) tests were performed to analyze antigenic characteristics of HA of BV strains.Results:Fifty-four BV strains were randomly selected to be analyzed further. Compared with the HA gene of this influenza season vaccine strain (B/Austria/1359417/2021), there are three amino acid mutations among all BV strains, two of which are located in two different antigenic determinants. Furthermore, the phylogenetic tree analysis revealed that only one subgroup of 1A.3a.2 was circulating simultaneously. All BV strains are located in Clade 1A.3a.2 subgroup, and in the same subgroup with that of the vaccine component BV strain in 2023-2024. All BV strains have the same glycosylation sites as that of the vaccine component BV strain in 2023-2024. Antigenic analysis showed that all BV strains were antigenically similar with its vaccine strain.Conclusions:In the 2023-2024 influenza surveillance season, the prevalent BV strains in the population in Beijing city are located in Clade 1A. 3a. 2 subgroup. The antigen matching between BV epidemic strains and vaccine BV components is relatively high during this surveillance season.
4.Impact of circadian clock protein Bmal1 on experimentally-induced periodontitis-associated renal injury
Haonan MA ; Qiong LI ; Yaqi SHANG ; Xirui XIN ; Xinchan LIU ; Zhou WU ; Weixian YU
West China Journal of Stomatology 2024;42(2):163-171
Objective To investigate the mechanism of circadian clock protein Bmal1(Bmal1)on renal injury with chronic periodontitis,we established an experimental rat periodontitis model.Methods Twelve male Wistar rats were randomly divided into control and periodontitis groups(n=6,each group).The first maxillary molars on both sides of the upper jaw of rats with periodontitis were ligated by using orthodontic ligature wires,whereas the control group re-ceived no intervention measures.After 8 weeks,clinical periodontal parameters,including probing depth,bleeding index,and tooth mobility,were evaluated in both groups.Micro-CT scanning and three-dimensional image recon-struction were performed on the maxillary bones of the rats for the assessment of alveolar bone resorption.Histopatholo-gical observations of periodontal and renal tissues were conducted using hematoxylin-eosin(HE)and periodic acid-Schiff(PAS)staining.Renal function indicators,such as creatinine,albumin,and blood urea nitrogen levels,and oxida-tive stress markers,including superoxide dismutase,glutathione,and malondialdehyde levels,were measured using bio-chemical assay kits.MitoSOX red staining was used to detect reactive oxygen species(ROS)content in the kidneys.The gene and protein expression levels of Bmal1,nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)in rat renal tissues were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)and immuno-histochemical staining.Results Micro-CT and HE staining results showed significant bone resorption and attachment loss in the maxillary first molar region of the periodontitis group.Histological examination through HE and PAS staining revealed substantial histopathological damage to the renal tissues of the rats in the periodontitis group.The findings of the assessment of renal function and oxidative stress markers indicated that the periodontitis group exhibited abnormal levels of oxidative stress,whereas the renal function levels showed abnormalities without statistical significance.Mito-SOX Red staining results showed that the content of ROS in the renal tissue of the periodontitis group was significantly higher than that of the control group,and RT-qPCR and immunohistochemistry results showed that the expression levels of Bmal1,Nrf2,and HO-1 in the renal tissues of the rats in the periodontitis group showed a decreasing trend.Conclu-sion Circadian clock protein Bmal1 plays an important role in the oxidative damage process involved in the renal of rats with periodontitis.
5.Role of connexin 43 in a rat model of periodontitis-induced renal injury
Yu XIN ; Ruobing FU ; Xirui XIN ; Yaqi SHANG ; Xinchan LIU ; Weixian YU
West China Journal of Stomatology 2024;42(3):296-303
Objective This study aims to investigate the role of gap junction mediated by connexin 43(Cx43)in renal injury induced by periodontitis in rats.Methods Twelve SPF-grade Wistar male rats were divided into a control group and a periodontitis group by using a completely random number table method,with six rats in each group.The control group rats were not treated,while the periodontitis group rats were subjected to wire ligation of the neck of their bilateral maxillary first molars to construct a periodontitis model.After 8 weeks of modeling,the rats were examined for clinical indicators of the periodontium.micro-CT scanning of the maxilla reconstructed its 3D structure and analyzed the absorption of alveolar bone.Histopathological changes in periodontal and renal tissues were detected.MitoSOX red reagent was used to determine reactive oxygen species(ROS)content in renal tissues.A biochemical reagent kit was used to detect serum oxidative stress biomarkers.Real-time fluo-rescent quantitative-polymerase chain reaction(qRT-PCR)was employed to determine Cx43,nuclear factor kappa-B(NF-κB),interleukin(IL)-1β,IL-6,BCL2-Associated X(Bax),B-lymphomatoma-2 gene(Bcl-2),and Caspase-3 mRNA were determined.Western blot analysis was used to detect Cx43,NF-κB,IL-1β,Bax,Bcl-2 and Caspase-3 protein.Re-sults micro-CT 3D reconstruction showed significant bone resorption of the first molar alveolar bone in the periodonti-tis group rats and decreased height of the alveolar ridge.The distance from the enamel cementum boundary to the top of the alveolar ridge in the periodontitis group was significantly higher than that inthe control group.The histopathological results showed a large number of inflammatory cells that infiltrated the periodontal tissue of the periodontitis group,and the alveolar bone was significantly absorbed.Rats in the periodontitis group also exhibited mild thickening of the glomer-ular basement membrane,dilation of the Bowman's capsule,and destruction of the brush-like edge of the renal tubules in the renal tissue.The MitoSOX red staining results showed a significant increase in ROS content in the renal tissue of the periodontitis group.The biochemical test results showed that the levels of superoxide dismutase and glutathione in the serum of rats with periodontitis decreased,while that of malondialdehyde increased.The results of qRT-PCR and Western blot showed that the expression levels of Cx43,IL-1β,IL-6,Bax,Caspase-3 mRNA and Cx43,IL-1β,NF-κB,Bax,Caspase-3 proteins in the periodontitis group significantly increased compared with those in the control group,while the expression levels of Bcl-2 mRNA and protein decreased.Conclusion Periodontitis may activate NF-κB sig-naling molecules by upregulating the expression of Cx43 in rat kidney tissues,leading to increased levels of inflamma-tion and apoptosis and ultimately inducing kidney injury.
6.The role of uncoupling protein 2 in experimental periodontitis-associated renal injury in rats
Qiong LI ; Haonan MA ; Yaqi SHANG ; Xirui XIN ; Xinchan LIU ; Zhou WU ; Weixian YU
West China Journal of Stomatology 2024;42(4):502-511
Objective This study aims to explore changes in uncoupling protein 2(UCP2)in experimental periodonti-tis-associated renal injury induced by ligation and investigate the effect of UCP2 on renal injury induced by periodontitis.Methods Twelve Wistar male rats were randomly divided into two groups:control and periodontitis groups.A periodon-tal model was built by ligating the maxillary first molars area with 0.2 mm orthodontic ligature wire.After 8 weeks,the in-traoral condition of the rats was observed and periodontal clinical indices such as gingival bleeding index(BI),periodontal probing depth(PD),and tooth mobility(TM)were detected.The maxillary bone was scanned by Micro CT to observe the alveolar bone resorption.The tissue mineral density(TMD),bone mineral density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),trabecular bone separation(Tb.Sp)were recorded,and the distance from the enamel bone boundary to the alveolar crest(CEJ-ABC)of the maxillary first molar was measured.The oxidative stress indexes such as malondialdehyde,glutathione(GSH),and superoxide dismutase(SOD)were detected using frozen rat kidney tissue.The gene expression of UCP2,nuclear factor erythroid 2-related factor 2(Nrf2),and peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)was observed by quantitative real-time polymerase chain reaction(qRT-PCR)test.The gingival tissue of the rats was used for immunohistochemical staining to observe the expression of the UCP2 protein.The fixed rat kidney tissue was used for hematoxylin-eosin(HE),periodic acid-schiff(PAS),MitoSOX Red,JC-1,and immu-nohistochemical staining to observe the renal histopathology,the level of reactive oxygen species(ROS),the level of mito-chondrial membrane potential,and the expression of UCP2,Nrf2,and PGC-1α protein.Rat serum was collected to detect renal function indices,namely,blood urea nitrogen(BUN),creatinine(Cre),and albumin(Alb).Results Compared with the control group,the periodontitis group showed red,swollen,and soft gingival tissue,with gingival probing bleeding,periodontal PD increased,tooth loosening,alveolar bone resorption,decreased TMD,BMD,BV/TV,and Tb.Th indices,and increased Tb.Sp index,CEJ-ABC,and gingival UCP2 protein expression.Compared with the control group,the levels of MDA and ROS in the kidney tissue of periodontitis rats and the gene and protein expression of UCP2 increased,and the levels of MMP,GSH,and SOD and the gene and protein expression of Nrf2 and PGC-1α decreased.Renal functional indi-ces,namely,BUN,Cre,and Alb,were not significantly different between the two groups.Conclusion UCP2 may play a role in renal injury induced by periodontitis through oxidative stress.
7.Evaluation of Coronary Microcirculatory Function in Patients With Hypertrophic Cardiomyopathy and Analysis of Preliminary Results
Haobo XU ; Fasheng ZHU ; Weixian YANG ; Jiansong YUAN ; Juan WANG ; Tianjie WANG ; Yilu LIU ; Yong WANG ; Tao TIAN ; Shubin QIAO
Chinese Circulation Journal 2024;39(10):983-988
Objectives:To evaluate the coronary microcirculatory function in patients with hypertrophic cardiomyopathy(HCM). Methods:Patients who diagnosed with HCM and underwent the measurement of index of microcirculatory resistance(IMR)using pressure-sensing guide wire from November 2021 to April 2023 were prospectively included.Coronary microcirculatory dysfunction(CMD)was defined as IMR≥25 U and patients were grouped accordingly to compare the clinical characteristics. Results:A total of 25 HCM patients were included.Mean age was(58.4±13.3)years,18 were men and mean body mass index was(26.7±3.6)kg/m2.Coronary microcirculatory function was successfully evaluated in all patients and the mean value of IMR was(30.5±15.3)U.There were 15 patients with CMD.Baseline clinical characteristics,laboratory examinations and medications were simialr between patients with and without CMD.The maximal left ventricular wall was significant thicker in patients with CMD compared with that in patients without CMD([20.2±2.8]mm vs.[16.9±2.3]mm,P=0.005).There was no significant difference in other echocardiographic parameters between two groups(all P>0.05).In the range of IMR value less than 50 U(n=22),there was a significant linear positive correlation between maximal left ventricular wall thickness and IMR(r=0.423,P=0.049).There was no significant difference in coronary flow reserve and fractional flow reserve between two groups. Conclusions:The severity of CMD is positively correlated with left ventricular wall thickness in HCM patients.
8.Constructing a predictive model for tsutsugamushi disease complicated with sepsis based on decision tree and logistic regression
LIU Xing ; LI Weixian ; ZHANG Le
China Tropical Medicine 2024;24(9):1066-
Abstract: Objective To explore the optimal prediction model for tsutsugamushi disease complicated with sepsis through decision tree models and logistic regression models. Methods A total of 235 cases of tsutsugamushi disease patients admitted to the Third People's Hospital of Kunming from June 2012 to December 2023 were selected as the research subjects, including 138 cases of tsutsugamushi disease patients with sepsis as the experimental group and 97 cases of tsutsugamushi disease patients without sepsis as the control group. Decision tree models and logistic regression models were established, and the discriminability of two prediction models was compared using receiver operating curve (ROC) to assess their predictive abilities. Results Among 235 patients, Han ethnicity accounted for 91.1%, farmers accounted for 66.8%, and those residing in suburban areas accounted for 57.4%. The clinical manifestations were mainly fever, headache, and chills, with an incidence rate of scab of 100.0%. Factors that were statistically significant between the two groups included age, IL-1β, IL-2, IL-17, IFN-γ, and TNF-α (P<0.05). The above factors were brought into the logistic regression model and decision tree model, respectively. The multivariate analysis results of logistic regression showed that age (OR=1.039, 95%CI:1.017-1.061) and IFN-γ (OR=1.009, 95%CI:0.999-1.018) were independent influencing factors for tsutsugamushi disease complicated with sepsis. The area under the ROC curve (AUC) was 0.669 (95CI:0.599-0.738, P<0.001), with an accuracy of 63.8%, sensitivity of 71.1%, and specificity of 57.2%. The decision tree model results showed that the root node was IL-1β, and the sub-nodes were age and IL-2. The area under the ROC curve (AUC) was 0.714 (95CI:0.646-0.782, P<0.001), with an accuracy of 68.9%, sensitivity of 58.8%, and specificity of 76.1%. Comparing the two models, the AUC difference was 0.045, the standard error was 0.042, Z=1.074, P=0.283, 95%CI: -0.037-0.128. In terms of treatment and prognosis, doxycycline was used most frequently (78.3%), and the combination of doxycycline and moxifloxacin was the most common (87.7%) in combined treatments. There was a strong positive correlation between the duration of medication and the frequency of combined treatments (τ=0.119, P=0.021), as well as between the duration of medication and hospitalization time (τ=0.725, P<0.001). The clinical diagnostic rate was 94.5%, and the mortality rate was 1.7%. Conclusions Both models have certain predictive values, among which the decision tree model has better predictive ability and is worthy of clinical promotion.
9.Research progress of the regulation effect of traditional Chinese medicine monomer of flavonoids on the pulmonary fibrosis signaling pathway
Jianhua MENG ; Rui LIU ; Ling PAN ; Zhenzhen LUO ; Weixian SONG ; Jue LU
China Pharmacy 2023;34(18):2293-2298
Pulmonary fibrosis is a chronic, progressive and irreversible interstitial lung disease. At present, there is no specific drug for the treatment of pulmonary fibrosis, and many TCM monomers have potential therapeutic value for pulmonary fibrosis, among which flavonoids are the main representative. For example, total flavones of Astragalus memeranaceus and scutellarin can reduce inflammatory cell infiltration, lung injury and extracellular matrix (ECM) deposition by interfering with transforming growth factor-β1/drosophila MAD protein signaling pathway. Total flavonoids of Oxytropis falcata Bunge and salidroside can inhibit lung inflammation by mediating JAK/signal transduction and transcriptional activator signaling pathway, and prevent the epithelial interstitial transition (EMT) process. Quercetin and Ginkgo biloba leaf extract can reduce the apoptosis of macrophages by inhibiting the nuclear factor-κB signaling pathway and play an anti-pulmonary fibrosis role. Urushetin and proanthocyanidins can promote the morphological recovery of myofibroblasts and reduce ECM deposition through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target protein of rapamycin signaling pathway. Naringin and luteolin can inhibit scorch death of macrophage and inflammation response, and improve lung function and lung tissue injury through NOD-like receptor heat protein domain related protein 3 signaling pathway. The ethanol extract of Phyllanthus emblica and calycosin can improve the inflammatory injury and fibrosis of lung tissue by activating the signaling pathway of nuclear transcription factor erythro2-related factor 2/antioxidant response element. Isogliquiritin can inhibit the phenotypic transformation of epithelial cells and reverse EMT progression by inhibiting extracellular signal-regulating kinase signaling pathway. In the future, scholars should consider developing appropriate drug carriers to improve their bioavailability and further study drug targets and pathways, to provide evidence for the development of traditional Chinese medicine monomers of flavonoids into clinical practice.
10.Phylogenetic and antigenic analysis of HA gene of influenza virus B (Victoria) in Beijing during 2021-2022 surveillance season
Guilan LU ; Shujuan CUI ; Jiachen ZHAO ; Yimeng LIU ; Weixian SHI ; Zhaomin FENG ; Yang PAN ; Daitao ZHANG ; Peng YANG ; Quanyi WANG ; Xiaomin PENG
Chinese Journal of Microbiology and Immunology 2023;43(8):619-626
Objective:To investigate the phylogenetic and antigenic characteristics of hemagglutinin (HA) gene of influenza B/Victoria lineage (BV) viruses in Beijing during the 2021-2022 influenza surveillance season, and to analyze whether the circulating BV viruses match the vaccine strain.Methods:Pharyngeal swab specimens from influenza like-illness (ILI) cases in the 2021-2022 influenza surveillance season were collected from surveillance network labs in Beijing and cultured in MDCK cells and chicken embryo to isolate BV viruses. Nucleic acids of the viruses were extracted, and the HA gene was amplified and sequenced. The nucleotide and amino acid sequence identity of the HA gene was analyzed using MEGA5.0 software. A phylogenetic tree of HA gene was constructed using the maximum likelihood method. The N-glycosylation sites in HA were predicted online. Three-dimensional structure of HA was constructed using SWISS-MODEL homologous modeling. Hemagglutination inhibition (HI) test was performed to analyze the antigenicity of BV viruses.Results:A total of 402 BV viruses were collected and 58 strains with full-length HA gene sequences were chosen for further analysis. Compared with the HA gene of this year′s vaccine strain (B/Washington/02/2019), there were 27 amino acid mutations, 11 of which were located in four different antigenic determinants. The phylogenetic analysis revealed that three subgroups of 1A.3, 1A.3a1, and 1A.3a2 co-circulated in Beijing with 54 strains (54/58, 93.10%) clustered to the Clade 1A.3a2, two strains (2/58, 3.45%) clustered to the Clade 1A.3a1, and two strains (2/58, 3.45%) in the same subgroup (Clade 1A.3) as the vaccine component BV strain in 2021-2022. Compared with the vaccine strain (B/Washington/02/2019), two BV strains had an additional N-glycosylation site at residue 197, while the other 56 strains showed no change in N-glycosylation sites. Antigenic analysis showed that 35 BV strains (35/58, 60.34%) were antigenically similar to the vaccine strain and 23 strains (23/58, 39.66%) were low-response strains.Conclusions:Three subgroups of BV viruses co-circulated in Beijing during the 2021-2022 influenza surveillance season. The predominant subgroup was Clade 1A.3a2 (93.10%), showing a certain genetic distance with the vaccine strain (B/Washington/02/2019). Nearly 40% (39.66%) of the viruses were low-response strains. This study indicated that continuous monitoring of the variations of influenza epidemic strains and timely providing laboratory basis for screening vaccine component strains were the basic technical guarantee for coping with influenza pandemic.

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