1.Huangqi Baijiang Yiren Decoction Restores Intestinal Mucosa Barrier in Rat Model of Ulcerative Colitis via miR-21/SOCS1/JAK1/STAT6 Signaling Pathway
Ruiping LI ; Shiyu WANG ; Xiunan WEI ; Ermei WU ; Dajuan SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):96-104
ObjectiveTo explore the potential mechanism by which Huangqi Baijiang Yiren decoction (HBY) repairs the intestinal mucosal injury in the rat model of ulcerative colitis (UC) via the miR-21/suppressor of cytokine signaling 1 (SOCS1)/Janus kinase 1 (JAK1)/signal transducer and activator of transcription 6 (STAT6) signaling pathway. MethodsSixty SPF-grade male SD rats were randomly assigned into six groups: blank, model, low-dose (3.68 g·kg-1) HBY, medium-dose (7.35 g·kg-1) HBY, high-dose (14.5 g·kg-1) HBY, and mesalazine (0.035 g·kg-1), with 10 rats in each group. The rat model of UC was established in other groups except the blank group by 3% dextran sulfate sodium solution. The rats were administrated with corresponding drugs once a day for 7 consecutive days since the 3th day after modeling. The histopathological changes of the colon were observed by hematoxylin-eosin staining, and the Robarts histopathology index (RHI) was scored. Enzyme-linked immunosorbent assay was employed to measure the levels of pro-inflammatory cytokines [interleukin (IL)-6, IL-18, IL-1β, and tumor necrosis factor-α (TNF-α)] in the serum. Real-time PCR was employed to determine the mRNA levels of miR-21, SOCS1, JAK1, and STAT6 in the colon tissue. Western blot was employed to determine the protein levels of SOCS1, JAK1, phosphorylated (p)-JAK1, STAT6, p-STAT6, Occludin, and Claudin-1 in the colon tissue. ResultsCompared with the blank group, the model group showed an increase in disease activity index (DAI) (P<0.01), shortening of colon length (P<0.01), severe histopathological damage in the colon tissue, and an increase in RHI, rises in serum levels of IL-6, IL-1β, IL-18, and TNF-α (P<0.01), up-regulation in mRNA levels of miR-21, JAK1, and STAT6 and protein levels of p-JAK1 and p-STAT6 (P<0.01), and down-regulation in mRNA and protein levels of SOCS1 and protein levels of Occludin and Claudin-1 (P<0.01). The treatment with HBY reduced the DAI (P<0.01), alleviated colon shortening and histopathological damage in the colon tissue, decreased the RHI (P<0.01), lowered the serum levels of IL-6, IL-1β, IL-18, and TNF-α (P<0.01), down-regulated the mRNA levels of miR-21, JAK1, and STAT6 (P<0.05, P<0.01), up-regulated the mRNA level of SOCS1 (P<0.05), up-regulated the protein levels of SOCS1, Occludin, and Claudin-1 (P<0.05, P<0.01), and down-regulated the protein levels of p-JAK1 and p-STAT6 (P<0.05, P<0.01). ConclusionHBY may modulate the miR-21/SOCS1/JAK1/STAT6 signaling pathway to suppress inflammatory responses and restore the intestinal mucosal barrier in UC rats.
2.A real-world study of vedolizumab versus infliximab in patients with moderate to severe ulcerative colitis
Ruiping MENG ; Baobao HUANG ; En LIU ; Hui LIN ; Cheng LIU ; Haoqi WEI ; Jiaqing SU ; Jianyun ZHOU ; Xia XIE
Journal of Army Medical University 2024;46(12):1417-1424
Objective To compare the efficacy and safety of vedolizumab(VDZ)and infliximab(IFX)for moderate to severe ulcerative colitis(UC)patients through a multicenter retrospective cohort study.Methods All patients with moderate to severe UC who were naive to biologic agents and treated with IFX or VDZ for at least 14 weeks at 3 hospitals in Southwest China between January 2021 and January 2023 were retrospectively enrolled.The efficacy evaluation indicators,including steroid-free clinical remission rates,clinical remission rates and endoscopic remission rates at weeks 14 and 52 were compared between the 2 groups.The occurrence of adverse events during treatment were recorded.Taking whether mucosal healing could be achieved after 14 and 52 weeks of treatment as the dependent variable,firstly,univariate analysis was performed to analyze the risk factors affecting mucosal healing at weeks 14 and 52,and then multivariate logistic regression analysis was applied to identify the independent risk factors of mucosal healing at the 2 time points.Results A total of 151 patients with moderate to severe UC were included,after propensity score matching(PSM),each group included 57 patients.There were no significant differences in the steroid-free clinical remission rate and clinical remission rate between the 2 groups at weeks 14 and 52(P>0.05).The endoscopic remission rate at week 14 was significantly higher in the VDZ group than the IFX group[40.4%(23/57)vs 22.8%(13/57),P=0.044],but no such difference was observed at week 52[64.5%(20/31)vs 59.5%(22/37),P=0.669].Multivariate logistic regression analysis showed that left-sided disease(E2)[vs pancolitis(E3)](OR=0.46,95%CI:0.21~0.98,P=0.045)was independent risk factor for mucosal healing at week 14 and a disease duration ≥36 months(OR=0.25,95%CI:0.09~0.66,P=0.005)was independent risk factor for mucosal healing at week 52.No statistical difference was observed in the incidence of adverse events between the 2 groups(1.8%vs 7.0%,P=0.360).Conclusion VDZ and IFX have similar efficacy and safety,and both can be used as first-line options for patients with moderate to severe UC.
3.Influencing factors of reflux esophagitis after sleeve gastrectomy and its plus procedures
Shibo LIN ; Wei GUAN ; Jiajia SHEN ; Yiming SI ; Ruiping LIU ; Hui LIANG
Chinese Journal of Digestive Surgery 2023;22(8):1003-1008
Objective:To investigate the influencing factors of reflux esophagitis after sleeve gastrectomy and its plus procedures.Methods:The retrospective case-control study was conducted. The clinical data of 130 patients who underwent sleeve gastrectomy and its plus procedures (jejunal bypass, duodenal-jejunal bypass) for the treatment of metabolic diseases in the First Affiliated Hospital of Nanjing Medical University from May 2010 to August 2021 were collected. There were 34 males and 96 females, aged (32±8)years, with the body mass index (BMI) as (38±7)kg/m 2. Observation indicators: (1) incidence of reflux esophagitis before and after surgery; (2) clinical manifestations of reflux esophagitis and treatment; (3) influencing factors of reflux esopha-gitis after surgery; (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. In univariate analysis, the median value of clinical variable was used for grouping and the chi-square test was used for subsequent analysis. Multivariate analysis was conducted using Logistic stepwise regression model. Results:(1) Incidence of reflux esophagitis before and after surgery. Of 130 patients, there were 5 cases with Los Angeles classification grade A reflux esopha-gitis before the surgery, and there were 35 cases with reflux esophagitis after surgery, including 26 cases as Los Angeles classification grade A esophagitis, 8 cases as Los Angeles classification grade B esophagitis and 1 case as Los Angeles classification grade C esophagitis. There was a significant difference in the incidence of reflux esophagitis for patients before and after surgery ( P<0.05). (2) Clinical manifestations of reflux esophagitis and treatment. The 5 patients with preoperative reflux esophagitis described with no obvious heartburn and acid regurgitation and did not receive treat-ment. For the 35 patients with postoperative reflux esophagitis, 22 cases described with heartburn and acid regurgitation, and 13 cases described without any symptoms. Of the 35 patients, 10 were treated with continuous oral proton pump inhibitors, 2 were treated with intermittent oral proton pump inhibitors, 10 were relieved by dietary adjustment, and 13 were not treated. For the 95 patients without postoperative reflux esophagitis, 5 cases described with heartburn and acid regurgitation, requiring continuous oral proton pump inhibitor treatment. The remaining 90 cases described no heartburn and acid regurgitation and did not receive treatment. (3) Influencing factors of reflux esophagitis after surgery. Results of multivariate analysis showed that the preoperative reflux diagnostic questionnaire scoring >0 and the occurrence of postoperative heartburn and acid regurgi-tation were independent risk factors of postoperative reflux esophagitis ( odds ratio=7.84, 47.16, 95% confidence interval as 2.04?30.20, 11.58?192.11, P<0.05). (4) Follow-up. All 130 patients were followed up for 17(range, 12?60)month after surgery. The BMI, percentage of total weight loss, diabetes remission rate, fasting blood glucose and glycosylated hemoglobin of the 130 patients at postoperative 12 month were (25±4)kg/m 2, 31%±8%, 84.6%(22/26), (5.6±1.2)mmol/L and 5.9%±1.3%. Conclusions:The sleeve gastrectomy and its plus procedures increase the risk of postoperative reflux esophagitis. Preoperative reflux diagnostic questionnaire scoring>0 and the occurrence of postoperative heartburn and acid regurgitation are independent risk factors of postoperative reflux esophagitis. Dietary adjustment and proton pump inhibitor therapy can alleviate symptoms of reflux esophagitis, but cannot cure reflux esophagitis.
4.Effects of intravenous thrombolysis combined with Xingnaojing injection on intracranial arterial hemodynamic indexes and neurological function in patients with cerebral infarction
Fangrui LI ; Yu LIAN ; Ming JING ; Xiaomeng JIN ; Wei LIU ; Ruiping CHEN ; Xiuying BAO ; Songtao GUO ; Zhanshan SUN
Chinese Journal of Primary Medicine and Pharmacy 2023;30(4):486-491
Objective:To investigate the effects of intravenous thrombolysis combined with Xingnaojing injection on hemodynamic indexes and neurological function in patients with cerebral infarction. Methods:A total of 142 patients with cerebral infarction who were treated in Xing An Meng Hospital from April 2020 to May 2021 were included in this study. They were randomly divided into a control group ( n = 71, intravenous thrombolysis) and a Xingnaojing injection group ( n = 71, intravenous thrombolysis + Xingnaojing injection). Intracranial arterial hemodynamic indexes, National Institutes of Health Stroke Scale score, Fugl-Meyer Assessment Scale score, serum inflammatory factors, oxidative stress indexes, brain injury markers, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly lower in the Xingnaojing injection group than the control group [interleukin-1β: (4.05 ± 0.83) ng/L vs. (6.85 ± 1.02) ng/L, interleukin-6: (43.61 ± 5.14) ng/L vs. (60.31 ± 7.04) ng/L, tumor necrosis factor-α: (35.93 ± 4.25) ng/L vs. (20.93 ± 3.11) ng/L, t = 17.94, 16.14, 15.37, all P < 0.001]. After treatment, the mean blood flow velocities of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery in the Xingnaojing injection group were significantly higher than those in the control group [anterior cerebral artery: (49.36 ± 5.28) cm/s vs. (41.15 ± 5.12) cm/s, middle cerebral artery: (61.27 ± 7.02) cm/s vs. (50.19 ± 6.08) cm/s, posterior cerebral artery: (44.92 ± 5.63) cm/s vs. (37.26 ± 4.93) cm/s, t = 9.40, 10.05, 8.62, all P < 0.001]. After treatment, the National Institutes of Health Stroke Scale score and Fugl-Meyer Assessment Scale score in the Xingnaojing injection group were superior to those in the control group [National Institutes of Health Stroke Scale score: (10.36 ± 1.52) points vs. (14.62 ± 2.05) points, Fugl-Meyer Assessment Scale score: (76.19 ± 8.08) points vs. (65.28 ± 7.14) points, t = 14.06, 8.52, both P < 0.05]. After treatment, the serum level of malondialdehyde in the Xingnaojing injection group was significantly higher than that in the control group [(6.35 ± 1.02) μmol/L vs. (10.05 ± 1.63) μmol/L), t = 16.21, P < 0.001]. The serum level of superoxide dismutase in the Xingnaojing injection group was significantly lower than that in the control group [(114.31 ± 13.69) U/L vs. (92.25 ± 10.16) U/L), t = 10.90, P < 0.001]. Serum levels of neuron-specific enolase and S100β in the Xingnaojing injection group were significantly lower than those in the control group [neuron-specific enolase: (24.01 ± 3.24) IU/L vs. (30.31 ± 4.02) IU/L, S100β: (0.73 ± 0.17) ng/L vs. (1.13 ± 0.22) ng/L, t = 10.28, 12.12, both P < 0.001). There was a significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Intravenous thrombolysis combined with Xingnaojing injection for the treatment of cerebral infarction can improve intracranial hemodynamics, reduce the inflammatory response and oxidative stress, and alleviate brain tissue injury. The combined therapy is beneficial to protect the neurological function of patients with cerebral infarction and is highly safe.
5.Status and significance of BCR-ABL1 kinase domain mutations in imatinib-resistant chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia patients from Northeast China
Yang TANG ; Ruiping HU ; Kaili XU ; Yehui TAN ; Wei HAN ; Chunshui LIU
Journal of Leukemia & Lymphoma 2022;31(1):26-31
Objective:To explore the characteristics of BCR-ABL1 kinase domain mutations in imatinib-resistant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients from Northeast China and their impact on prognosis. Methods:The clinical data of 252 CML patients and 49 Ph + ALL patients who were admitted to the First Hospital of Jilin University from January 2013 to October 2018 were retrospectively analyzed. The samples of bone marrow or peripheral blood were collected from patients when imatinib treatment was not effective. Nested polymerase chain reaction (PCR) was used to amplify the BCR-ABL1 kinase domain, and Sequencing Analysis v5.4 software was used to analyze the mutation of BCR-ABL1 kinase domain. Patients were followed up for 6-48 months, and the survival analysis was performed. Results:Among 252 CML patients, the mutations in ABL1 kinase domain were found in 57 patients (22.6%), including 25 patients in the chronic phase, 21 patients in the accelerated phase and 11 patients in the blast crisis; 50 patients had 20 types of single point mutation, and the most common mutation types were E255K (16.0%, 8/50), T315I (14.0%, 7/50), M244V (8.0%, 4/50) and G250E (8.0%, 4/50), which were all concentrated in the P-loop and C-helix domains; 7 patients had double mutations; patients with multiple mutations had the worst prognosis, with a median overall survival (OS) time of 3.2 months. Among 49 Ph + ALL patients, 17 cases (34.7%) were positive for mutations in the BCR-ABL1 kinase domain, 14 patients had 12 types of single point mutation, and 3 patients had multiple mutations; the median OS time of patients with multiple mutations, mutations located in the P-loop and C-helix domains and mutations located in the other domains was 2.0, 8.0 and 18.0 months, and the difference in OS among the three groups was statistically significant ( P < 0.01). Conclusions:Among the imatinib-resistant CML and Ph + ALL patients from Northeast China, point mutations in the P-loop and C-helix domains are most commonly found. Multiple mutations, mutations in the P-loop and C-helix domains are related to the poor prognosis of the patients.
6.Clinical value of monitoring serum CTRP3 and Lp-PLA2 levels in patients with coronary heart disease
Yun ZHOU ; Lilong WEI ; Ruiping ZHANG ; Yongtong CAO
Chinese Journal of Laboratory Medicine 2021;44(7):609-614
Objective:To investigate the clinical value of monitoring serum complement C1q/tumor necrosis factors-associated protein 3 (CTRP3) and lipoprotein-associated phospholipase A2(Lp-PLA2) levels in patients with coronary heart disease, especially patients with acute myocardial infarction (AMI).Methods:This case-control study included 99 patients with angina pectoris aged (60.4±10.4) years, 105 patients with AMI aged (61.7±14.3) years, and 60 healthy individuals aged (43.6±9.5) years. Serum CTRP3 was detected by ELISA, and Lp-PLA2 was detected by automatic biochemical analyzer. Logistic regression analysis was performed to determine the correlation between CTRP3, Lp-PLA2 in angina pectoris and AMI patients. The diagnostic efficiency of each index was analyzed by receiver operating characteristic (ROC) curve.Results:Serum Lp-PLA2 was significantly higher in AMI group than in angina pectoris group ([313.1±68.1] U/L vs [205.8±71.4] U/L, P<0.001), while CTRP3 was significantly lower in AMI group than in angina pectoris group ([64.2±18.5] μg/L vs [84.8±25.0] μg/L, P<0.001). Logistic regression showed that serum CTRP3 was negatively correlated with AMI ( OR=0.964, 95% CI 0.935-0.993, P=0.019), and Lp-PLA2 was positively correlated with AMI ( OR=1.020, 95% CI 1.008-1.032, P=0.001). ROC analysis showed that the AUC (95% CI) of AMI diagnosed by CTRP3 was 0.753 (0.685-0.821), P<0.001; the AUC (95% CI) of AMI diagnosed by Lp-PLA2 was 0.884 (0.833-0.935), P<0.001; the AUC (95% CI) of diagnosis efficacy by combined indices was 0.910 (0.870-0.950), P<0.001. Conclusions:Lower serum CTRP3 and higher serum Lp-PLA2 levels are associated with increased risk for AMI. Combined detection of both indices can improve the diagnostic efficacy of AMI.
7.Efficacy of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) therapy in the primary prevention of concurrent chemoradiotherapy-induced neutropenia
Yang CHEN ; Wei WANG ; Ruiping ZHANG ; Ransheng LIU ; Aixu ZHANG ; Zhizhen WANG
Chinese Journal of Radiation Oncology 2021;30(1):66-70
Objective:To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) therapy in the primary prevention of concurrent chemoradiotherapy-induced neutropenia.Methods:In this single-center, open-label, single-arm clinical observation, the efficacy of PEG-rhG-CSF in the primary prevention of neutropenia after concurrent chemoradiotherapy in 58 patients admitted to Tianjin Medical University Cancer Institute and Hospital from June 2018 to June 2019 was evaluated.Results:During the whole concurrent chemoradiotherapy, chemotherapy delay occurred in 6 patients (10%). Three patients (5%) had delayed concurrent chemotherapy due to leukopenia or neutropenia. The completion rate of chemotherapy cycle was 94.6%(106/112). Radiotherapy delay occurred in 10 patients (17%) including 2 patients (3%) of delayed radiotherapy due to leukopenia or neutropenia. No patient developed febrile neutropenia (FN). Subgroup analysis found that after completing 1 cycle of concurrent chemoradiotherapy, the incidence rates of grade 4 leukopenia and neutropenia were both 0. After completing 2 cycles of concurrent chemoradiotherapy, the incidence rates of grade 4 leukopenia and neutropenia were 0 and 2%.Conclusion:During the chemoradiotherapy, application of PEG-rhG-CSF in the primary preventation can significantly reduce the incidence of FN, grade 4 leukopenia and neutropenia, which is beneficial to ensure the smooth progress of concurrent chemoradiotherapy.
8.MRI feature of hepatic epithelioid hemangioendothelioma
Ke WU ; Wei XU ; Ruiping CHANG ; Xinghua ZHANG ; Haiyi WANG ; Huiyi YE
Chinese Journal of Hepatobiliary Surgery 2018;24(6):367-370
Objective To discuss the MRI findings of hepatic epithelioid hemangioendothelioma (EHE).Methods MRI and clinical data of 8 EHE patients confirmed by pathology in PLA General Hospital were retrospectively analyzed.Results 8 patients included 3 male and 5 female.1 patient had single lesion and 7 patients had multiple lesions.A total of 162 lesions were detected and most of the lesions were in the peripheral liver.For T1WI,100 lesions (61.7%) showed slightly low signal,and 62 lesions (38.3%) showed lower signal intensity in the center of the lesion and appeared as "target sign".For T2WI,the center of 29 lesions (17.9%) showed two-loop "target sign",66 lesions (40.7%) showed three-loop "target sign",and 67 lesions (41.4%) showed slightly homogeneous higher signal.For DWI,116 lesions (71.6%) showed halo-like high signal and 46 lesions (28.4%) showed uniform high signal.For dynamic enhancement,the lesions showed slightly enhancement in the arterial phase,and persistent enhancement in portal venous phase,the center of 122 lesions (about 75.3%) showed enhancement and 40 lesions (24.7%) showed no enhancement in delayed phase.1 patient with hepatobiliary specific contrast was enhanced in hepatobiliary phase.“Hepatic capsule depression” was observed in 30 lesions.7 lesions appeared as “lollipop sign”,and were enveloped in 16 lesions.Conclusion MRI,DWI and dynamic contrastenhanced scanning of EHE in liver are characteristic,which is helpful for qualitative diagnosis before surgery.
9.Expressing patterns of serum inflammatory factors in patients with gas-tric cancer with different types of tongue fur
Junfeng ZHANG ; Liwei ZHANG ; Juan WU ; Qianqian XIN ; Wei DONG ; Ruiping WANG ; Zhen ZHAN
Journal of Beijing University of Traditional Chinese Medicine 2018;41(5):405-412
Objective To investigate the expressing patterns of serum inflammatory factors in patients with gastric cancer(GC)with different types of tongue fur.Methods GC patients with different types of longue fur(n=134)and non-GC subjects with different types of tongue fur(n=93)were chosen from clinic.The levels of serum inflammatory factors were detected by using electro-chemiluminescence immu-noassay(ECLIA),and correlation between types of tongue fur and serum inflammatory factors was ana-lyzed by using multi-factor association method.Results The levels of serum interleukin-17α(IL-17α) had significant difference in GC patients with different types of longue fur(P<0.05).The analysis on fur color showed that level of serum IL-17αwas 3.062 ng/L in GC patients with yellow fur and 3.982 ng/L in those with white fur(P<0.05).ROC analysis showed that the sensitivity was 72.7%,specific-ity was 91.3%and AUC(95% CI)was 0.639(0.539 -0.739)of serum IL-17αin distinguishing white fur and yellow fur,and cutoff value was 6.033 ng/L.The similar tendency was identified in non-GC subjects.The correlation analysis showed that there were 20 serum inflammatory factors with signifi-cant positive correlation in GC patients with the same types of tongue fur,and significant negative correla-tion in GC patients with different types of tongue fur.Conclusion The level of IL-17αcan significantly distinguish white tongue fur and yellow tongue fur.The white-yellow tongue fur and thin-thick tongue fur may reflect adverse inflammatory status in GC patients.
10.Action verb processing for exciting the motor cortex and promoting the recovery of upper limb function after stroke
Sicong ZHANG ; Xiangtong JI ; Quan WANG ; Haofeng SHEN ; Yixi ZHU ; Ruiping HU ; Wei CHEN ; Tifei YUAN ; Chunlei SHAN
Chinese Journal of Physical Medicine and Rehabilitation 2017;39(6):412-417
Objective To explore the effect of action verb processing on the excitability of the motor cortex and any effect on the upper limb motor function of stroke survivors.Methods Experiment 1:The motor evoked potential by transcranial magnetic stimulation (TMS-MEP) was measured while 18 healthy subjects were processing concrete action verbs or abstract verbs.Experiment 2:Eight hemiplegic stroke survivors were asked to read silently text describing concrete hand actions,and then repeat and explain the meaning of the action verbs used in the text.This was repeated for 30 minutes per day,5 days per week for 3 weeks.In the 2nd week the same training was conducted except that the text was about abstract verbs.The modified Ashworth scale (MAS),Fugl-Meyer assessment (FMA),the Hong Kong version of the functional test for a hemiplegic upper extremity (FTHUE-HK) and a simple test for evaluating hand function (STEF) were used to assess upper limb motor function before and after the training each week.Results Experiment 1:Processing the concrete action verbs induced significantly greater MEP than processing the abstract verbs.Experiment 2:The average FMA and STEF ratings improved significantly after the training each week.Training with the concrete action verbs resulted in significantly better FMA and STEF scores than with the abstract verbs.The average MAS score increased significantly week by week.There was significantly more improvement in the average FTHUE-HK rating after the 1st and 3rd week of training than after the 2nd week.Conclusion Action verb processing induces greater motor cortex excitation than abstract verb processing among healthy subjects and better improves the upper limb motor function of stroke survivors.

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