1.Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione.
Fu'an XIE ; Yujia NIU ; Xiaobing CHEN ; Xu KONG ; Guangting YAN ; Aobo ZHUANG ; Xi LI ; Lanlan LIAN ; Dongmei QIN ; Quan ZHANG ; Ruyi ZHANG ; Kunrong YANG ; Xiaogang XIA ; Kun CHEN ; Mengmeng XIAO ; Chunkang YANG ; Ting WU ; Ye SHEN ; Chundong YU ; Chenghua LUO ; Shu-Hai LIN ; Wengang LI
Journal of Pharmaceutical Analysis 2025;15(1):101068-101068
Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [15N2]-cystine and [13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
2.Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione
Fu'an XIE ; Yujia NIU ; Xiaobing CHEN ; Xu KONG ; Guangting YAN ; Aobo ZHUANG ; Xi LI ; Lanlan LIAN ; Dongmei QIN ; Quan ZHANG ; Ruyi ZHANG ; Kunrong YANG ; Xiaogang XIA ; Kun CHEN ; Mengmeng XIAO ; Chunkang YANG ; Ting WU ; Ye SHEN ; Chundong YU ; Chenghua LUO ; Shu-Hai LIN ; Wengang LI
Journal of Pharmaceutical Analysis 2025;15(1):189-207
Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
3.Research progress on the relationship between Alzheimer's disease and obstructive sleep apnea
Dongmei LUO ; Tenghong LIAN ; Peng GUO ; Wei ZHANG
Chinese Journal of Geriatrics 2024;43(1):1-7
Alzheimer's disease(AD)is the most common cognitive disorder in the elderly and manifests primarily as progressive cognitive function decline, neuropsychiatric symptoms and multiple functional impairments.Obstructive sleep apnea(OSA)is a common type of respiratory disorder.Studies have found that AD and OSA are connected in many ways, including the risk of developing these diseases, biomarkers and neuroimaging features.These connections may result from a variety of mechanisms, such as neuropathological protein deposition, exacerbated immune-mediated inflammation, oxidative stress abnormalities, impaired mitochondrial function, and disturbed neurotransmitter systems, among others.This article reviewed the relationship between AD and OSA, the mechanisms linking them and their treatment.
4.Network Analysis-Based Identification of Core Symptoms in Different Chinese Medicine Syndromes During the Acute Phase of Ischemic Stroke
Lian GU ; Weitao WANG ; Dongmei LI ; Shengying LIU ; Xiaoxiao SONG ; Hong CAI ; Li SU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(11):2837-2845
Objective The study aimed to investigate the prevalence of various Traditional Chinese Medicine(TCM)syndromes during the acute phase of ischemic stroke and identify the key symptoms associated with each syndrome.Methods A total of 1011 patients in the acute phase of ischemic stroke were assessed for TCM syndromes using the"Diagnostic criteria for stroke in Traditional Chinese Medicine"within 72 h of symptom onset,on the 7th day post onset,and on the 14th day.R4.2.3 software was utilized to analyze the TCM syndromes and symptoms,as well as to conduct network analysis.Results The incidence of phlegm syndrome was the highest(54.10%,51.18%,49.39%)at 72 h,7th and 14th day of disease onset,respectively,followed by wind syndrome,fire-heat syndrome,blood stasis syndrome,qi deficiency syndrome and excessive yang due to yin deficiency syndrome.The incidence of wind syndrome gradually decreased over time(x2=15.619,P<0.001).In the network of 44 TCM syndrome entries,TZ-5(pulse)had the highest centrality index(strength=2.4)and was located at the most central position of the network.In the network analysis of different TCM syndrome,TZ-5(pulse)(strength=1.91)was located in the center of the phlegm syndrome network,FZ-1(onset)(strength=1.61)was located in the center of the wind syndrome network,HRZ-2(tongue coating)(strength=1.37)was located in the center of the network in the fire-heat syndrome,XYZ-1(tongue texture)(strength=1.18)was located at the center of the network for the blood stasis syndrome.Conclusion The phlegm syndrome is the most important syndrome in the acute phase of ischemic stroke.Employing network analysis can elucidate the central symptoms of different syndromes and the interconnections between the symptoms,providing new ideas for the identification of ischemic stroke.
5.Network Analysis-Based Identification of Core Symptoms in Different Chinese Medicine Syndromes During the Acute Phase of Ischemic Stroke
Lian GU ; Weitao WANG ; Dongmei LI ; Shengying LIU ; Xiaoxiao SONG ; Hong CAI ; Li SU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(11):2837-2845
Objective The study aimed to investigate the prevalence of various Traditional Chinese Medicine(TCM)syndromes during the acute phase of ischemic stroke and identify the key symptoms associated with each syndrome.Methods A total of 1011 patients in the acute phase of ischemic stroke were assessed for TCM syndromes using the"Diagnostic criteria for stroke in Traditional Chinese Medicine"within 72 h of symptom onset,on the 7th day post onset,and on the 14th day.R4.2.3 software was utilized to analyze the TCM syndromes and symptoms,as well as to conduct network analysis.Results The incidence of phlegm syndrome was the highest(54.10%,51.18%,49.39%)at 72 h,7th and 14th day of disease onset,respectively,followed by wind syndrome,fire-heat syndrome,blood stasis syndrome,qi deficiency syndrome and excessive yang due to yin deficiency syndrome.The incidence of wind syndrome gradually decreased over time(x2=15.619,P<0.001).In the network of 44 TCM syndrome entries,TZ-5(pulse)had the highest centrality index(strength=2.4)and was located at the most central position of the network.In the network analysis of different TCM syndrome,TZ-5(pulse)(strength=1.91)was located in the center of the phlegm syndrome network,FZ-1(onset)(strength=1.61)was located in the center of the wind syndrome network,HRZ-2(tongue coating)(strength=1.37)was located in the center of the network in the fire-heat syndrome,XYZ-1(tongue texture)(strength=1.18)was located at the center of the network for the blood stasis syndrome.Conclusion The phlegm syndrome is the most important syndrome in the acute phase of ischemic stroke.Employing network analysis can elucidate the central symptoms of different syndromes and the interconnections between the symptoms,providing new ideas for the identification of ischemic stroke.
6.Risk factors of bronchopulmonary dysplasia in very preterm infants: a national multicenter study
Ruihua BA ; Lixia TANG ; Wei SHEN ; Lian WANG ; Zhi ZHENG ; Xinzhu LIN ; Fan WU ; Qianxin TIAN ; Qiliang CUI ; Yuan YUAN ; Ling REN ; Jian MAO ; Yumei WANG ; Bizhen SHI ; Ling LIU ; Jinghui ZHANG ; Yanmei CHANG ; Xiaomei TONG ; Yan ZHU ; Rong ZHANG ; Xiuzhen YE ; Jingjing ZOU ; Huaiyu LI ; Baoyin ZHAO ; Yinping QIU ; Shuhua LIU ; Li MA ; Ying XU ; Rui CHENG ; Wenli ZHOU ; Hui WU ; Zhiyong LIU ; Dongmei CHEN ; Jinzhi GAO ; Jing LIU ; Ling CHEN ; Cong LI ; Chunyan YANG ; Ping XU ; Yayu ZHANG ; Sile HU ; Hua MEI ; Zuming YANG ; Zongtai FENG ; Sannan WANG ; Eryan MENG ; Lihong SHANG ; Falin XU ; Shaoping OU ; Rong JU
Chinese Pediatric Emergency Medicine 2022;29(6):433-439
Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.
7.The level and clinical value of fecal calprotectin in very low birth weight infants
Jinglin XU ; Bingbing LIAN ; Ruiquan WANG ; Lianqiang WU ; Dongmei CHEN ; Bin WU
Chinese Pediatric Emergency Medicine 2021;28(10):890-894
Objective:To understand the change trend and influencing factors of fecal calprotectin(FC) in very low birth weight(VLBW) infants, and to explore the application value of FC detection in the diagnosis of necrotizing enterocolitis(NEC) in VLBW infants.Methods:VLBW infants hospitalized in the neonatal department at Quanzhou Children′s Hospital from June 2018 to May 2019 were selected as research object for a prospective study.Fecal samples from the 1st, 7th, 14th, 21st, 28th and 35th days after birth and fecal samples from the acute and recovery stages of NEC were collected continuously.The content of FC was determined quantitatively by immunofluorescence assay.Results:(1) The FC level of non NEC VLBW infants from 1 to 35 days after birth was 143.5(47.8, 391.2) μg/g.Univariate analysis showed that the level of FC fluctuated with the postnatal age, the level of FC was the highest at 21 days, and then decreased.The level of FC increased significantly in formula feeding, premature rupture of membranes, neonatal sepsis, feeding intolerance and pregnant mothers without glucocorticoid before delivery( P< 0.05). (2) Multivariate covariance analysis showed that prenatal application of glucocorticoid( F=10.550, P=0.001), premature rupture of membranes( F=13.311, P<0.001), neonatal sepsis( F=8.001, P=0.005), feeding intolerance( F=4.751, P=0.030) and NEC( F=54.566, P<0.001) had significant effects on FC level.After controlling the effects of prenatal corticosteroid, premature rupture of membranes, neonatal sepsis and feeding intolerance, the levels of FC in NEC group and non-NEC group were 3 162.3(1 412.5-7 244.4)μg/g and 141.3(125.9-162.2)μg/g, respectively.In NEC group, the levels of FC in acute stage and recovery stage were 3 166.9(1 745.1, 6 806.4)μg/g and 130.9(97.4, 273.9)μg/g, respectively, with significant difference( t=10.304, P<0.001). While the levels of FC were 2 347.9(1 404.4, 5 893.4)μg/g in the mild NEC and 4 114.7(2 764.5, 9 208.4)μg/g in the moderate or severe NEC, respectively, with no significant difference( t=1.131, P=0.280). Conclusion:The levels of FC fluctuate with postnatal age and it is affected by multiple factors.FC maybe a useful marker for the diagnosis and evaluation of efficacy of NEC in VLBW infants.
8. Research advances in assessment tools for oral feeding readiness in preterm infants
Lili LI ; Hui ZHAO ; Dongmei LIAN ; Yanhui YANG
Chinese Journal of Practical Nursing 2019;35(16):1277-1281
In recent years, the oral feeding readiness for preterm infants has been paid more and more attention, and there are various assessment tools for the oral feeding readiness. The professionals in various countries have been constantly improved and adjusted according to the national and clinical conditions, but up to now, no unified standard has been formed. This paper reviews the assessment tools of preterm infant′s oral feeding readiness at home and abroad, and provides reference for the unified evaluation standard of preterm infant's oral feeding readiness, so as to establish more standardized and effective intervention strategies and enhance the effect of preterm infant′s oral feeding nursing.
9.Stressor, job burnout and anxiety of pediatric nurses of 5 Class Ⅲ Grade A hospitals of Beijing
Dongmei LIAN ; Jing SUN ; Lei CHENG ; Haixin BO ; Pengwei LU ; Aobo LIU
Chinese Journal of Modern Nursing 2018;24(23):2762-2766
Objective To explore the current situation of stressor,job burnout and anxiety of pediatric nurses of Class Ⅲ Grade A hospitals and to analyze the correlation between stressor and job burnout as well as stressor and anxiety.Methods From January to February 2017,a total of 233 pediatric nurses of 5 Class Ⅲ Grade A hospitals of Beijing were selected by convenience sampling as subjects.All of the pediatric nurses were investigated with the Nurse Job Stressor Scale (NJSS),Maslach Burnout Inventory-Human Services Survey (MBI-HSS),Self-Rating Anxiety Scale (SAS).Results Among 233 pediatric nurses,two dimensions of NJSS with high scores included time allocation and workload (2.69 ± 0.87) as well as patient care(2.54 ± 0.70).Two items of NJSS with high scores contained that the wages and other welfare treatment was low (3.04 ± 0.93) as well as worrying about mistakes and accidents in work (2.97 ± 0.97).The emotion exhaustion dimension of MBI-HSS was with 22.7% for the severe level.Patients with low scores of sense of personal achievement accounted for 41.2%.The score of SAS was (38.38 ± 7.47) significantly higher than Chinese model (t=17.57,P < 0.01).There were 10.7% of nurses with the moderate-severe level of anxiety.The correlation analysis among stressor,job burnout and anxiety of pediatric nurses showed that except for time allocation and workload as well as sense of personal achievement,other dimensions of NJSS had positive correlations with dimensions of MBI-HSS and SAS (r=0.169-0.527,P < 0.05).Conclusions Pediatric nurses are with high working pressure.Policy makers and managers should consider characteristics in pediatric nursing,reduce nurses' stressors as well as the level of nurses' job burnout and improve their mental health,so as to ensure the quality of pediatric nursing.
10.Medical compliance behavior among systemic lupus erythematosus children at a ClassⅢ Grade A hospital in Beijing
Jing SUN ; Yang LI ; Hongmei SONG ; Dongmei LIAN
Chinese Journal of Modern Nursing 2018;24(30):3690-3693
Objective To explore the medical compliance behavior among systemic lupus erythematosus (SLE) children so as to provide a basis for implementing targeted nursing intervention. Methods From November 2015 to October 2017, we selected 124 SLE children of Department of Pediatrics of Peking Union Medical College Hospital as subjects in by convenience sampling. The self-designed SLE Children Medical Compliance Behavior Questionnaire was used to the investigation. A total of 124 questionnaires were sent out and 116 valid questionnaires were collected. Results Among 116 children, the mean of total score of medical compliance behavior was (105.91±10.62) along with the highest score (4.91±0.43) in the term of"I will not presume to reduce the dose" belong to the dimension of medication and review. Conclusions SLE children have the high level of compliance in medication and review. Health care providers should continue to carry out sunscreen, choose appropriate diet, pay attention to the details of infection prevention and develop a regular exercise habit for children along with their patients so as to improve long-term prognosis and quality of life of SLE children.

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