1.Effect of rosavin on hepatocellular steatosis and its underlying mechanism
Shen WANG ; Jin-hui CAI ; Lin ZHENG ; Yan ZHANG ; Kai-qing ZENG ; Qi-en XU ; Yan-min FENG ; Xiao-xia YE
Chinese Pharmacological Bulletin 2025;41(3):466-474
Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.
2.Effect of rosavin on hepatocellular steatosis and its underlying mechanism
Shen WANG ; Jin-hui CAI ; Lin ZHENG ; Yan ZHANG ; Kai-qing ZENG ; Qi-en XU ; Yan-min FENG ; Xiao-xia YE
Chinese Pharmacological Bulletin 2025;41(3):466-474
Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.
3.Study on the toxicity characteristics of a clinical bloodstream isolate of Salmonella Telelkebir
En-Hui ZHENG ; Yu-Feng QIU ; Jian-Hui CHEN ; Ya-Dong GAO ; Meng-Ying HUANG ; Qu-Wen LI ; Jie LIN ; Shun-Tai WENG
Chinese Journal of Zoonoses 2024;40(1):31-39
The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.
4.Research progress on drug resistance mechanism of sorafenib in radioiodine refractory differentiated thyroid cancer
En-Tao ZHANG ; Hao-Nan ZHU ; Zheng-Ze WEN ; Cen-Hui ZHANG ; Yi-Huan ZHAO ; Ying-Jie MAO ; Jun-Pu WU ; Yu-Cheng JIN ; Xin JIN
The Chinese Journal of Clinical Pharmacology 2024;40(13):1986-1990
Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.
5.The distribution of blood pressure and associated factors of the elderly with type 2 diabetes in Jiangsu Province.
Jia Hui LIU ; Han Kun XIE ; Jian SU ; Zheng ZHU ; En Chun PAN ; Yan LU ; Fu Ping WAN ; Qing Yang YAN ; Ning ZHANG ; Shu Jun GU ; Ming WU ; Jin Yi ZHOU ; Chong SHEN
Chinese Journal of Preventive Medicine 2023;57(5):614-625
Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m2, fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m2, male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.
Adult
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Aged
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Humans
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Male
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Female
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Middle Aged
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Aged, 80 and over
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Blood Pressure/physiology*
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Diabetes Mellitus, Type 2/epidemiology*
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Antihypertensive Agents/therapeutic use*
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Smoking
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Body Mass Index
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Hypertension/epidemiology*
6.Preparation of 3D printed metoprolol tartrate chewable tablets and optimization of printing process
Shan-shan WANG ; Xiao-lu HAN ; En LIANG ; Cong-hui LI ; Chun-yan LIU ; Ming-yuan LI ; Zeng-ming WANG ; Peng YU ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2023;58(9):2811-2817
With the growing demand of personalized medicine for children, it is especially important to develop medicines for children. In this study, using metoprolol tartrate as model drug, we developed 3D printed chewable tablets suitable for children with automated dosage distribution using semi-solid extruded (SSE) 3D printing technology. Based on the quality by design concept, this study prepared a semi-solid material with good printability using gelatin as the substrate, constructed 3D models and printed tablets with the aid of computer-aided design. The printing parameters were optimized and determined as follows: print temperature of 35-37 ℃, print speed of 25 mm·s-1, fill rate of 15%, and number of outer profile layers of 2. Subsequently, the printing process and the quality uniformity of the tablets were verified, and a linear relationship between the dose and the number of model layers was obtained. Finally, 3D printed chewable tablets were superior in terms of appearance, dose accuracy and compliance compared with traditional split-dose commercially available tablets. In this study, 3D printed metoprolol tartrate chewable tablets with good performance were successfully prepared to address the personalized medication needs of pediatric patients.
7.A prospective cohort study on refractive status of schoolchildren in Huangzhong District, Xining City, Qinghai Province.
Qi LIN ; En Tuan YANG ; Li LI ; Ji Feng YU ; Xue LIU ; Hua Xin ZUO ; Man Jun LIU ; Hui Hui CHU ; Yin Zheng ZHAO ; Jidi ZHANG
Chinese Journal of Preventive Medicine 2022;56(9):1251-1256
Objective: To determine the characteristics and progress of the visual acuity and refractive state of schoolchildren in Huangzhong District, Xining City, Qinghai Province in China. Methods: Cohort study. Department of Ophthalmology, Beijing Children's Hospital carried out a cohort study by collecting the visual acuity and refractive state of Grade 1-5 schoolchildren among 16 primary schools in Huangzhong District, Xining City, Qinghai Province in September 2020 and July 2021. Cycloplegic retinoscopy with eye drop which contained tropicamide (0.5%) and phenylephrine hydrochloride (0.5%) was performed in children with low vision(<1.0). Myopia was defined as the spherical equivalent (SE) ≤-0.5 D after cycloplegic retinoscopy. Measurement data was analyzed by t-test and enumeration data was analyzed by χ2 test. Multiple linear regression was used to analyze the influencing factors. Results: The 2 489 individuals with repeated tests in two years were included in the follow-up study, among whom the prevalence of myopia was 26.24%(653/2 489) in 2020, while 32.94% (820/2 489)respectively in 2021. The incidence of myopia in one school year from grades 1 to 5 was 11.19%(47/420), 5.44%(21/386), 6.39%(25/391), 11.52%(44/382) and 11.67%(30/257). The average SE of children in all grades in 2021 increased negatively from the previous year (Grade 1 to Grade 5 increased respectively: 0.40 D, 0.69 D, 0.62 D, 0.52 D and 0.37 D). Conclusions: The prevalence of myopia among schoolchildren in Huangzhong District, Xining City, Qinghai Province was relatively high. There were two peaks of myopia incidence in the first, fourth and fifth grades. Female, age, and the baseline of SE were the related influencing factors for myopia progression.
Child
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Cohort Studies
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Female
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Follow-Up Studies
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Humans
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Mydriatics
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Myopia/epidemiology*
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Ophthalmic Solutions
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Phenylephrine
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Prevalence
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Prospective Studies
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Tropicamide
8.The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease
Cheng Han NG ; Kai En CHAN ; Yip Han CHIN ; Rebecca Wenling ZENG ; Pei Chen TSAI ; Wen Hui LIM ; Darren Jun Hao TAN ; Chin Meng KHOO ; Lay Hoon GOH ; Zheng Jye LING ; Anand KULKARNI ; Lung-Yi Loey MAK ; Daniel Q HUANG ; Mark CHAN ; Nicholas WS CHEW ; Mohammad Shadab SIDDIQUI ; Arun J. SANYAL ; Mark MUTHIAH
Clinical and Molecular Hepatology 2022;28(3):565-574
Background/Aims:
Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals.
Methods:
Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk.
Results:
Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality.
Conclusions
Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.
9.Effect of electroacupuncture on small airway function in patients with stable chronic obstructive pulmonary disease.
Ying HE ; Gui-Yuan LI ; Ze-Guang ZHENG ; Yi GAO ; Jun-Hui PAN ; Feng WANG ; Wan-Yi HUANG ; Yan GE ; Guang-En ZHONG ; Juan TONG
Chinese Acupuncture & Moxibustion 2021;41(8):861-865
OBJECTIVE:
To observe the regulatory effect of electroacupuncture (EA) on small airway function and exercise tolerance in patients with stable chronic obstructive pulmonary disease (COPD).
METHODS:
A total of 62 patients with stable COPD were randomized into an observation group (31 cases, 1 case dropped off) and a control group (31 cases, 5 cases dropped off). On the base of routine medication and aerobic exercise, the patients of the two groups all received EA at Danzhong (CV 17), Rugen (ST 18), Guanyuan (CV 4), Zhongwan (CV 12), Tianshu (ST 25) and Yingchuang (ST 16). In the observation group, filiform needles were used and inserted perpendicularly, 3 mm in depth. In the control group, the placebo needling method was performed, in which the needle was not inserted through skin at each point. In both groups, electric stimulation with low-frequency electronic pulse instrument was exerted, with continuous wave, 2 Hz in frequency, lasting 30 min each time in the two groups. The treatment was given once every other day, 3 times a week, for 14 treatments totally. Before and after treatment, the following indexes were compared in patients between the two groups, i.e. the lung function indexes (forced expiratory volume in first second [FEV1], forced vital capacity [FVC], the ratio of FEV1 to FVC [FEV1/FVC], maximal voluntary ventilation [MVV], the percentage of maximal expiratory flow [MEF] at 25% of FVC exhaled [MEF25], MEF50 and MEF75 in predicted value), cardiopulmonary exercise test indexs (metabolic equivalent [METS], oxygen uptake per kg body weight [VO
RESULTS:
After treatment, FVC%, MVV%, MEF75%, MEF50%, VO
CONCLUSION
Electroacupuncture can improve the respiratory function and exercise tolerance in COPD patients through removing small airway obstruction and increasing ventilation.
Electroacupuncture
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Exercise Tolerance
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Forced Expiratory Volume
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Humans
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Pulmonary Disease, Chronic Obstructive/therapy*
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Respiratory Function Tests
10.Bivariate heritability estimation of resting heart rate and common chronic disease based on extended pedigrees.
Hong Chen ZHENG ; En Ci XUE ; Xue Heng WANG ; Xi CHEN ; Si Yue WANG ; Hui HUANG ; Jin JIANG ; Ying YE ; Chun Lan HUANG ; Yun ZHOU ; Wen Jing GAO ; Can Qing YU ; Jun LV ; Xiao Ling WU ; Xiao Ming HUANG ; Wei Hua CAO ; Yan Sheng YAN ; Tao WU ; Li Ming LI
Journal of Peking University(Health Sciences) 2020;52(3):432-437
OBJECTIVE:
To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes.
METHODS:
The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables.
RESULTS:
The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120-0.407), 0.404 (95%CI: 0.135-0.673), and 0.799 (95%CI: 0.590-1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120-1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181-0.788, P<0.05).
CONCLUSION
Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.
Blood Pressure
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Chronic Disease
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Female
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Heart Rate
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Humans
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Hypertension
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Male
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Middle Aged
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Pedigree

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