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):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.
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):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.
3.Expert Consensus on Perioperative Nursing Care for Follicular Unit Extraction(2025)
Chunhua ZHANG ; Weiwei BIAN ; Congmin WANG ; Lin SHEN ; Yong MIAO ; Na LIU ; Shan JIA ; Junhong AN ; Hongxia WANG ; Dongmei ZHANG
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1606-1613
To promote the standardization and normalization of perioperative care for follicular unit extraction(FUE) hair transplantation, ensure treatment efficacy, and align with advancements in the specialty, the Nursing Branch of the Chinese Association of Plastic and Aesthetics organized a panel of domestic experts. By integrating evidence-based medicine with clinical practice experience, and following thorough discussions, these experts developed the Clinical Practice
4.Effect of comprehensive interventions to pulmonary rehabilitation on prevention of ventilator-associated pneumonia in elderly patients undergoing long-term mechanical ventilation
Jionghe WU ; Dan WANG ; Jiangqiong SHEN ; Dongmei LI ; Jing ZHAO
Chinese Journal of Nosocomiology 2025;35(22):3378-3382
OBJECTIVE To explore the effect of comprehensive interventions to pulmonary rehabilitation on preven-tion of ventilator-associated pneumonia(VAP)in elderly patients undergoing long-term mechanical ventilation.METHODS A total of 154 elderly patients(aged no less than 80 years old)who received long-term me-chanical ventilation(no less than 21 days)in the Second Medical Center of Chinese PLA General Hospital from Nov.2018 to Dec.2024 were recruited as the research subjects and were randomly divided into the comprehen-sive intervention group with 77 cases(routine nursing plus comprehensive interventions to pulmonary rehabilita-tion)and the routine nursing group with 77 cases.RESULTS The incidence of VAP was 12.31%in the comprehen-sive intervention group,30.65%in the routine nursing group(P=0.009);the off-ventilator oxyhemoglobin satu-ration was(92.29±5.78)%in the comprehensive intervention group at the end of observation period,(88.84±4.70)%in the routine nursing group(P<0.001);the diaphragmatic thickening ratio was(36.78±16.06)%in the comprehensive intervention group,(25.02±19.97)%in the routine nursing group(P<0.001);the 24-hour ex-pectoration volume was(94.68±26.65)ml in the comprehensive intervention group,(64.61±15.16)ml in the routine nursing group(P<0.001);all the above indexes were improved.The result of multivariate logistic regres-sion analysis showed that no interventions to pulmonary rehabilitation(OR=2.763,95%CI:1.061 to 7.195)and mechanical ventilation(OR=1.107,95%CI:1.033 to 1.186)were the risk factors for VAP(P<0.05).CONCLUSIONS The comprehensive interventions to pulmonary rehabilitation can remarkably improve the respira-tory function of the elderly patients undergoing mechanical ventilation and reduce the incidence of VAP.The ex-tension of mechanical ventilation may increase the risk of VAP.
5.Effect of comprehensive interventions to pulmonary rehabilitation on prevention of ventilator-associated pneumonia in elderly patients undergoing long-term mechanical ventilation
Jionghe WU ; Dan WANG ; Jiangqiong SHEN ; Dongmei LI ; Jing ZHAO
Chinese Journal of Nosocomiology 2025;35(22):3378-3382
OBJECTIVE To explore the effect of comprehensive interventions to pulmonary rehabilitation on preven-tion of ventilator-associated pneumonia(VAP)in elderly patients undergoing long-term mechanical ventilation.METHODS A total of 154 elderly patients(aged no less than 80 years old)who received long-term me-chanical ventilation(no less than 21 days)in the Second Medical Center of Chinese PLA General Hospital from Nov.2018 to Dec.2024 were recruited as the research subjects and were randomly divided into the comprehen-sive intervention group with 77 cases(routine nursing plus comprehensive interventions to pulmonary rehabilita-tion)and the routine nursing group with 77 cases.RESULTS The incidence of VAP was 12.31%in the comprehen-sive intervention group,30.65%in the routine nursing group(P=0.009);the off-ventilator oxyhemoglobin satu-ration was(92.29±5.78)%in the comprehensive intervention group at the end of observation period,(88.84±4.70)%in the routine nursing group(P<0.001);the diaphragmatic thickening ratio was(36.78±16.06)%in the comprehensive intervention group,(25.02±19.97)%in the routine nursing group(P<0.001);the 24-hour ex-pectoration volume was(94.68±26.65)ml in the comprehensive intervention group,(64.61±15.16)ml in the routine nursing group(P<0.001);all the above indexes were improved.The result of multivariate logistic regres-sion analysis showed that no interventions to pulmonary rehabilitation(OR=2.763,95%CI:1.061 to 7.195)and mechanical ventilation(OR=1.107,95%CI:1.033 to 1.186)were the risk factors for VAP(P<0.05).CONCLUSIONS The comprehensive interventions to pulmonary rehabilitation can remarkably improve the respira-tory function of the elderly patients undergoing mechanical ventilation and reduce the incidence of VAP.The ex-tension of mechanical ventilation may increase the risk of VAP.
6.Correlation between serum thymosin α1 and cardiac function in patients with acute anterior wall ST-segment elevation myocardial infarction
Zhenfa ZHOU ; Cuifen HU ; Dongmei SHI ; Liang LIU ; Chengxing SHEN
Journal of Interventional Radiology 2024;33(7):717-722
Objective To explore the correlation between serum thymosin α1 level and left ventricular ejection fraction(LVEF)in patients with acute anterior wall ST-segment elevation myocardial infarction(STEMI)after receiving percutaneous coronary intervention(PCI).Methods A total of 74 patients with acute anterior wall STEMI(acute anterior wall STEMI group)and 38 patients having no myocardial infarction(control group),who were admitted to the Shanghai Sixth People's Hospital of China from December 2019 to February 2022,were enrolled in this study.According to the LVEF value after the recanalization of anterior descending coronary artery with PCI during hospitalization period,the patients of acute anterior wall STEMI group were divided into LVEF<50%subgroup(n=33)and LVEF≥50%subgroup(n=41).Serum thymosin α1 level was determined by enzyme linked immunosorbent assay(ELISA),the results were compared between the groups.Logistic regression analysis was used to analyze the correlation between thymosin α1 level and LVEF.The receiver operating characteristic(ROC)curve of serum thymosin α1 level for predicting cardiac function in patients with acute anterior wall STEMI after receiving PCI was drawn.Results The serum thymosin α1 level in LVEF≥50%subgroup was significantly higher than that in the LVEF<50%subgroup(P=0.032).During the post-PCI hospitalization period,the serum thymosin α1 level was positively correlated with LVEF.Logistic regression analysis revealed that serum thymosin α1 level was an independent predictor for LVEF<50%in patients with acute anterior wall STEMI after receiving PCI.The area under ROC of serum thymosin α1 level for predicting LVEF≥50%in patients with acute anterior wall STEMI during hospitalization was 0.644(P=0.034).The area under ROC of serum thymosin α1 level combined with peak troponin I level and with peak NT-proBNP level for predicting LVEF<50%in patients with acute anterior wall STEMI during hospitalization was 0.780(P<0.01)and 0.702(P=0.003)respectively.When taking the median serum thymosin α1 level as the cut-off value,the proportion of LVEF≥50%patients was higher among the patients having the post-PCI serum thymosin α1 level>2,890 ng/L.Conclusion In patients with acute anterior wall STEMI,the serum thymosin α1 level is closely related to the LVEF value during the post-PCI hospitalization period,it is an independent predictor for cardiac function improvement after PCI.It is expected that the serum thymosin α1 level may become a new indicator for predicting the improvement of cardiac function in patients with STEMI after recanalization of anterior descending coronary artery with PCI.
7.Association between the visceral adiposity index and cognitive decline in community-dwelling elderly residents
Yang HE ; Xinyu XIE ; Wei SHEN ; Weiwei ZHANG ; Yuhao GE ; Dongmei KANG
Chinese Journal of Geriatrics 2024;43(3):361-365
Objective:To investigate the relationship between the visceral adiposity index(VAI) and cognitive decline.Methods:A cross-sectional study was conducted.Between October 2020 and March 2023, 483 elderly residents living in communities in Hefei were recruited and divided into four groups based on VAI scores, Q1(VAI ≤ 1.14), Q2(VAI>1.15 and ≤1.85), Q3(VAI>1.86 and ≤2.81) and Q4(VAI>2.82).General cognitive function was assessed by(MMSE)and(MoCA).Attention and working memory were tested by forward and backward digit span tasks.Logistic regression was utilized to analyze the relationship between different VAI scores and insulin resistance.The correlation between different VAI scores and cognitive function domains was analyzed by partial correlation.Results:The values of BMI, fasting plasma glucose, fasting insulin, HbA1c, high-sensitivity C-reactive protein, HOMA-IR and HOMA-β increased with increasing VAI scores(all P<0.01).VAI was significantly correlated with insulin sensitivity after adjusting for confounding factors including sex.The risk of insulin resistance in Q4 was 7.40 times that in Q1( OR=7.40, 95% CI: 4.30-12.74, P<0.05).In addition, the correlation coefficients between VAI and forward digital span and between VAI and backward digital span were -0.116 and -0.105, respectively(both P<0.05), but there was no correlation between VAI and MMSE or MoCA. Conclusions:VAI is closely related to insulin resistance and also associated with early cognitive decline in elderly people with visceral obesity.
8.Production of 2-18F-fluorobutyric acid as a PET imaging agent for prostate cancer
Weixuan DONG ; Kaixin QIN ; Cong SHEN ; Dongmei SHI ; Wenhao HU ; Xiaoyi DUAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):1020-1026
[Objective] In view of the crucial role of indole propionic acid in the treatment of tumor immune checkpoint blockade and further revealing its mechanism, our study intended to design and synthesize 1-[18F]-fluoroethyl-indole propionic acid (1-[18F]-IPA), and evaluate it as a tumor PET imaging agent. [Methods] The precursor 1-(2-p-toluenesulfonic acid oxygen ethyl)-methyl indole propionate underwent nucleophilic substitution reaction with 18F-. The crude product was separated and purified by high-performance liquid chromatography and the intermediates were collected. Finally, 1-[18F]-IPA was obtained by hydrolysis. The clarity of the product was measured by visual inspection, the pH value was determined by precision test paper, and the radiochemical purity and stability were determined by high-performance liquid chromatography. In order to determine the biodistribution of 1-[18F]-IPA in normal mice, ICR mice were intravenously injected with 1-[18F]-IPA (0.2 mL, 7 MBq), and sacrificed at 5, 15, 25, 45, 75 and 120 min and dissected. Micro-PET imaging was performed and analyzed in BxPC-3 tumor-bearing nude mice. Student t test was used to compare the biodistribution of tissues and organs at different time points. [Results] The total preparation time of 1-[18F]-IPA was 35-40 min, the radiochemical yield was (45±5)%, and the radiochemical purity was more than 95%. The product solution was clear without particles, and the pH value was 6.5, which had good stability in vitro and in vivo. The results of biodistribution in healthy ICR mice showed that except for the brain, 1-[18F]-IPA had a certain uptake in all major organs, with the most obvious uptake in the liver, gallbladder and kidneys. The radioactivity in the gallbladder gradually increased with time and reached (39.86±6.56)%ID/g at 120 min, but bone uptake did not change significantly with time. Micro-PET/CT showed that there was radioactive uptake at the tumor 30 min after injection of 1-[18F]-IPA in Dutch BxPC-3 nude mice, but it was not obvious. At this time, SUVmax was about 55.18±14.62. Consistent with the results of biodistribution, the brain uptake was low at each time point. [Conclusion] In summary, 1-[18F]-IPA with short preparation time and high yield is expected to be a tool to probe tryptophan indole metabolism pathway and further reveal tumor immune resistance.
9.Epidemiological characteristics of mycoplasma pneumoniae infection in hospitalized children between 2019 -2022
Dongmei QIU ; Feifei SHEN ; Liyuan SHEN ; Youjia WU
Journal of Public Health and Preventive Medicine 2024;35(4):83-86
Objective To explore the epidemiological characteristics of mycoplasma pneumoniae (MP) infection in hospitalized children between 2019 and 2022, and to provide a basis for the prevention and treatment of the disease in the clinic. Methods Blood samples of 12 830 children hospitalized for respiratory tract infection in our hospital between January 2019 and December 2022 were collected, and tested for MP infection, then the prevalence of MP infection in different years, seasons, genders and ages was analyzed. Results The total positive rate of MP was 16.55% (2 123 / 12 830). The annual prevalence rate of MP infection decreased from 17.97% in 2019 to 16.48% in 2022, with statistical difference (P<0.05). In terms of gender, the prevalence of MP infection was higher in females at a rate of 19.38% (1 198 / 6 182) compared with a rate of 13.91% (925 / 6 648) in males, with statistical difference (χ2=69.277, P<0.05).The positive rates in summer (19.84%) and autumn (19.57%) were higher than those in spring (12.97%) and winter (12.38%) (P<0.05) In terms of age, the positive rate of MP infection was 9.68% in < 1 age group, 12.95% in 1-3 age group, 18.23% in 4-6 age group and 23.23% in > 6 age group (P<0.05), with the highest positive rate in > 6 age group. The positive rate of MP infection was 15.49% in acute upper respiratory tract infection , 17.28% in acute lower respiratory tract infection , 16.43% in severe pneumonia, and 16.71% in other diseases, with no statistical difference (P>0.05). Conclusion MP is one of the main pathogens of respiratory infections in hospitalized children. Despite the decreasing trend in MP infection rate in hospitalized children between 2019 and 2022, it remains above the norm. MP infection is characterized by a high prevalence in summer and autumn, children >6 years of age, and girls, so effective measures should be taken to guide clinical anti-infection strategies to improve the physical and mental health of children in this region.
10.Antimicrobial resistance profile of clinical isolates in hospitals across China:report from the CHINET Antimicrobial Resistance Surveillance Program,2023
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Hua FANG ; Penghui ZHANG ; Bixia YU ; Ping GONG ; Haixia SHI ; Kaizhen WEN ; Yirong ZHANG ; Xiuli YANG ; Yiqin ZHAO ; Longfeng LIAO ; Jinhua WU ; Hongqin GU ; Lin JIANG ; Meifang HU ; Wen HE ; Jiao FENG ; Lingling YOU ; Dongmei WANG ; Dong'e WANG ; Yanyan LIU ; Yong AN ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Jianping WANG ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Cunshan KOU ; Shunhong XUE ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Xiaoyan ZENG ; Wen LI ; Yan GENG ; Zeshi LIU
Chinese Journal of Infection and Chemotherapy 2024;24(6):627-637
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0% were gram-positive and 71.0% were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6%,81.9% and 78.5%,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9% of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4% of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1% in the isolates from children and and 95.9% in the isolates from adults.The resistance rate to carbapenems was lower than 15.0% for most Enterobacterales species except for Klebsiella,22.5% and 23.6% of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6% to 10.0%.The resistance rate to imipenem and meropenem was 21.9% and 17.4% for Pseudomonas aeruginosa,respectively,and 67.5% and 68.1% for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.


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