1.Effect of pegylated interferon-α-2b therapy on cytotoxicity of virus-specific CD8+ T cells in HBeAg-negative patients with chronic hepatitis B virus infection
Lei QIN ; Guangpeng LI ; Peijun SHEN ; Lanfang ZHANG ; Xiaofei YANG ; Meijuan PENG ; Ye ZHANG
Journal of Clinical Hepatology 2025;41(4):628-636
ObjectiveTo investigate the change in the activity of hepatitis B virus (HBV)-specific CD8+ T cells after pegylated interferon-α-2b (PEG-IFN-α-2b) therapy in HBeAg-negative patients with chronic HBV infection. MethodsA total of 53 HBeAg-negative patients with chronic HBV infection who attended The First Affiliated Hospital of Xinxiang Medical University and Tangdu Hospital of Air Force Mdical University from April 2020 to June 2022 were enrolled and treated with PEG-IFN-α-2b (180 μg/week, subcutaneous injection) antiviral therapy. The study endpoint was HBsAg clearance (course of treatment<48 weeks) or 48 weeks (course of treatment≥48 weeks). Peripheral blood mononuclear cells were isolated at baseline and study endpoint, and peripheral blood T cell counts were measured. Enzyme-linked immunospot assay was used to measure the frequency of HBV-specific CD8+ T cells secreting perforin, granzyme B, and interferon-γ. A total of 17 HLA-A*02-restricted patients were selected, and CD8+ T cells were purified to establish direct- and indirect-contact co-culture systems for HBV-specific CD8+ T cells and HepG2.2.15 cells. The level of lactate dehydrogenase in supernatant was measured to calculate the mortality rate of HepG2.2.15 cells, and the levels of HBV DNA, cytotoxic molecules, and cytokines in supernatant were also measured. Flow cytometry was used to measure the expression of apoptosis ligands, and the cytotoxicity of HBV-specific CD8+ T cells was evaluated. The independent samples t-test or the paired t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test or the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsThe HBsAg clearance rate at study endpoint was 30.19% (16/53). There were no significant differences in peripheral blood T cell counts (CD3+, CD4+, and CD8+ T cells) between baseline and study endpoint (P>0.05). At study endpoint, there was a significant increase in the frequency of HBV-specific CD8+ T cells secreting perforin, granzyme B, and interferon-γ (U=177.50, t=11.90, U=186.50, all P<0.001), and the patients with HBsAg clearance had a significantly higher frequency of such HBV-specific CD8+ T cells than those without HBsAg clearance (U=120.50, t=2.73, U=121.50, all P<0.01). In the direct- and indirect-contact co-culture systems at study endpoint, HBV-specific CD8+ T cells induced a significant reduction in HBV DNA in the supernatant of HepG2.2.15 cells (all P<0.001) and significant increases in the secretion of interferon-γ and tumor necrosis factor-α (all P<0.05); in the direct-contact co-culture system, HBV-specific CD8+ T cells induced significant increases in the mortality rate of HepG2.2.15 cells (13.62%±3.27% vs 11.39%±2.40%, t=2.27, P=0.030) and the secretion of perforin and granzyme B (t=72.50, U=52.50, both P<0.05). In the direct- and indirect-contact co-culture systems, compared with HBV-specific CD8+ T cells from the patients without HBsAg clearance, the HBV-specific CD8+ T cells from patients with HBsAg clearance had a significantly greater reduction in HBV DNA (P<0.05) and significant increases in the secretion of interferon-γ and tumor necrosis factor-α (P<0.05). ConclusionPEG-IFN-α-2b therapy can help to achieve a relatively high HBsAg clearance rate in HBeAg-negative patients with chronic HBV infection, and the activity of HBV-specific CD8+ T cells is significantly enhanced, which is closely associated with HBsAg clearance.
2.Analysis of the content of five radionuclides in wild edible fungi
Zhenglin YE ; Qiang ZHOU ; Fei TUO ; Baolu YANG ; Zeshu LI ; Weihao QIN ; Shuying KONG
Chinese Journal of Radiological Health 2025;34(2):242-248
Objective To determine the content and distribution characteristics of the artificial radionuclide 137Cs and the natural radionuclides 210Pb, 226Ra, 228Ra, and 40K in wild edible fungi, and calculate the committed effective dose due to 137Cs and 210Pb in wild edible fungi. Methods Thirty samples of wild edible fungi were collected and their caps and stems were separated. A total of 60 samples were measured for 137Cs, 210Pb, 226Ra, 228Ra, and 40K using a BE5030 wide-energy, low-background, high-purity germanium γ spectrometer. The paired analysis of the four radionuclides 226Ra, 210Pb, 137Cs, and 40K was performed using SPSS 11.5. Results Among the 60 samples, the detection rates and dry weight specific activity ranges of 137Cs, 210Pb, 226Ra, 228Ra, and 40K were 97% and 0.62-384 Bq/kg, 73% and 6.4-159 Bq/kg, 52% and 0.7-28.8 Bq/kg, 5% and 0.43-2.18 Bq/kg and 100% and (77.4-264) × 10 Bq/kg, respectively. Conclusion Based on the analysis of the 60 samples, the detection rate of radionuclides is in the order of 40K, 137Cs, 210Pb, 226Ra, and 228Ra. In terms of the specific activity, the distribution of 40K and 226Ra in wild edible fungi in the same region is basically uniform, while the content of 210Pb and 137Cs fluctuates in different samples. Although 137Cs and 210Pb can be detected in most of the wild edible fungi, the annual committed effective dose due to ingestion of wild edible fungi is negligible.
3.Standardization of outpatient medical record in rehabilitation setting
Ye LIU ; Qing QIN ; Haiyan YE ; Yifan TIAN ; Yingxin ZHANG ; Yaru YANG ; Zhongyan WANG ; Meng ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Fubiao HUANG ; Qiuchen HUANG ; Yiji WANG ; Di CHEN ; Zhuoying QIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):45-54
ObjectiveTo analyze the data structure and standards of rehabilitation outpatient medical records, to provide data support for improving the quality of rehabilitation outpatient care and developing medical insurance payment policies. MethodsBased on the normative documents issued by the National Health Commission, Basic Standards for Medical Record Writing and Standards for Electronic Medical Record Sharing Documents, in accordance with the Quality Management Regulations for Outpatient (Emergency) Diagnosis and Treatment Information Pages (Trial), reference to the framework of the World Health Organization Family of International Classifications (WHO-FICs), the data framework and content of rehabilitation outpatient medical records were determined, and the data standards were discussed. ResultsThis study constructed a data framework for rehabilitation outpatient medical records, including four main components: patient basic information, visit process information, diagnosis and treatment information, and cost information. Three major reference classifications of WHO-FICs, International Classification of Diseases, International Classification of Functioning, Disability and Health, and International Classification of Health Interventions,were used to establish diagnostic standards and standardized terminology, as well as coding disease diagnosis, functional description, functional assessment, and rehabilitation interventions, to improve the quality of data reporting, and level of quality control in rehabilitation. ConclusionThe structuring and standardization of rehabilitation outpatient medical records are the foundation for sharing of rehabilitation data. The using of the three major classifications of WHO-FICs is valuable for the terminology and coding of disease diagnosis, functional description and assessment, and intervention in rehabilitation outpatient medical records, which is significant for sharing and interconnectivity of rehabilitation outpatient data, as well as for optimizing the quality and safety of rehabilitation medical services.
4.Structure, content and data standardization of inpatient rehabilitation medical record summary sheet
Haiyan YE ; Qing QIN ; Ye LIU ; Yifan TIAN ; Yingxin ZHANG ; Yaru YANG ; Zhongyan WANG ; Meng ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Fubiao HUANG ; Qiuchen HUANG ; Yiji WANG ; Di CHEN ; Zhuoying QIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):55-66
ObjectiveTo explore the standardization of inpatient rehabilitation medical record summary sheet, encompassing its structure, content and data standards, to enhance the standardization level of inpatient rehabilitation medical record summary sheet, improve data reporting quality, and provide accurate data support for medical insurance payment, hospital performance evaluation, and rehabilitation discipline evaluation. MethodsBased on the relevant specifications of the National Health Commission's Basic Norms for Medical Record Writing, Specifications for Sharing Documents of Electronic Medical Records, and Quality Management and Control Indicators for Inpatient Medical Record Summary Sheet (2016 Edition), this study analyzed the structure and content of the inpatient rehabilitation medical record summary sheet. The study systematically applied the three major reference classifications of the World Health Organization Family of International Classifications, International Classification of Diseases (ICD-10/ICD-11, ICD-9-CM-3), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI Beta-3), for disease diagnosis, functional description and assessment, and rehabilitation intervention, forming a standardized terminology system and coding methods. ResultsThe inpatient rehabilitation medical record summary sheet covered four major sections: inpatient information, hospitalization information, diagnosis and treatment information, and cost information. ICD-10/ICD-11 were the standards and coding tools for admission and discharge diagnoses in the inpatient rehabilitation medical record summary sheet. The three functional assessment tools recommended by ICD-11, the 36-item version of World Health Organization Disability Assessment Schedule 2.0, Brief Model Disability Survey and Generic Functioning domains, as well as ICF, were used for rehabilitation functioning assessment and the coding of outcomes. ICHI Beta-3 and ICD-9-CM-3 were used for coding surgical procedures and operations in the medical record summary sheet, and also for coding rehabilitation intervention items. ConclusionThe inpatient rehabilitation medical record summary sheet is a summary of the relevant content of the rehabilitation medical record and a tool for reporting inpatient rehabilitation data. It needs to be refined and optimized according to the characteristics of rehabilitation, with necessary data supplemented. The application of ICD-11/ICD-10, ICF and ICHI Beta-3/ICD-9-CM-3 classification standards would comprehensively promote the accuracy of inpatient diagnosis of diseases and functions. Based on ICD-11 and ICF, relevant functional assessment result data would be added, and ICHI Beta-3/ICD-9-CM-3 should be used to code rehabilitation interventions. Improving the quality of rehabilitation medical records and inpatient rehabilitation medical record summary sheet is an important part of rehabilitation quality control, and also lays an evidence-based data foundation for the analysis and application of inpatient rehabilitation medical record summary sheet.
5.Life's Essential 8 scores, socioeconomic deprivation, genetic susceptibility, and new-onset chronic kidney diseases.
Panpan HE ; Huan LI ; Mengyi LIU ; Ziliang YE ; Chun ZHOU ; Yanjun ZHANG ; Sisi YANG ; Yuanyuan ZHANG ; Xianhui QIN
Chinese Medical Journal 2025;138(15):1835-1842
BACKGROUND:
The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between LE8 scores and the risk of chronic kidney disease (CKD) remains uncertain. We aimed to explore the association of LE8 scores with new-onset CKD and examine whether socioeconomic deprivation and genetic risk modify this association.
METHODS:
A total of 286,908 participants from UK Biobank and without prior CKD were included between 2006 and 2010. CVH was categorized using LE8 scores: low (LE8 scores <50), moderate (LE8 scores ≥50 but <80), and high (LE8 scores ≥80). The study outcome was new-onset CKD, ascertained by data linkage with primary care, hospital inpatient, and death data. Cox proportional hazard regression models were used to investigate the association between CVH categories and new-onset CKD.
RESULTS:
During a median follow-up of 12.5 years, 8857 (3.1%) participants developed new-onset CKD. Compared to the low CVH group, the moderate (adjusted hazards ratio [HR], 0.50; 95% confidence interval [CI]: 0.47-0.53) and high CVH (adjusted HR, 0.31; 95% CI: 0.27-0.34) groups had a significantly lower risk of developing new-onset CKD. The population-attributable risk associated with high vs. intermediate or low CVH scores was 40.3%. Participants who were least deprived ( vs. most deprived; adjusted HR, 0.75; 95% CI: 0.71-0.79) and with low genetic risk of CKD ( vs. high genetic risk; adjusted HR, 0.89; 95% CI: 0.85-0.94) had a significantly lower risk of developing new-onset CKD. However, socioeconomic deprivation and genetic risks of CKD did not significantly modify the relationship between LE8 scores and new-onset CKD (both P -interaction >0.05).
CONCLUSION
Achieving a higher LE8 score was associated with a lower risk of developing new-onset CKD, regardless of socioeconomic deprivation and genetic risks of CKD.
Humans
;
Renal Insufficiency, Chronic/epidemiology*
;
Male
;
Female
;
Middle Aged
;
Genetic Predisposition to Disease/genetics*
;
Aged
;
Risk Factors
;
Adult
;
Proportional Hazards Models
;
Socioeconomic Factors
6.Regulation of apoptosis and autophagy in hepatoblastoma cells by Ganoderma lucidum polysaccharides through Akt/mTOR pathway.
Yang GE ; Hang GAO ; Yun-Peng QIN ; Rui SHEN ; Hua-Zhang WU ; Ting YE ; Hang SONG
China Journal of Chinese Materia Medica 2025;50(9):2432-2441
This research investigated the impact of Ganoderma lucidum polysaccharides(GLP) on hepatoblastoma HepG2 and Huh6 cell models, as well as KM mouse model with in situ transplanted tumors, so as to provide a theoretical basis for the clinical application of GLP. Cell viability was assessed through the CCK-8 assay, whereas cell proliferation was evaluated by using the BeyoClick~(TM)EdU-488 test. Cell apoptosis was visualized via Hochest 33258 staining, and autophagy was detected through Mrfp-GFP-LC3 dual fluorescence staining. An in situ tumor transplantation model was created by using HepG2 cells in mice, and mice were treated with normal saline and GLP of 100, 200, and 300 mg·kg~(-1) for tumor count calculation and size assessment. Hematoxylin-eosin(HE) staining was used to observe pathological changes in tumor tissue and vital organs(liver, kidney, lung, spleen, and heart). Western blot analysis was conducted to measure the protein expressions of tumor protein P53(P53), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved-caspase-3, Beclin-1, autophagy related protein-5(Atg-5), microtubule-associated protein-light chain-3Ⅰ(LC3Ⅰ)/LC3Ⅱ, autophagy adapter protein 62(P62), protein kinase B(Akt), p-Akt, mammalian target of rapamycin(mTOR), and p-mTOR. The in vitro experiment revealed that compared with the control group, after GLP treatment, tumor cell viability decreased significantly; apoptosis rate increased in a dose-dependent manner, and autophagic flux was inhibited. The in vivo experiments showed that compared with the model group, mice treated with GLP exhibited significantly fewer and smaller tumors. Western blot results showed that compared with the control group or model group, levels of P53, Bax, cleaved-caspase-3, Beclin-1, Atg-5, and LC3-Ⅱ/LC3-Ⅰ were significantly increased after GLP treatment, and the levels of Bcl-2, P62, p-Akt/Akt, and p-mTOR/mTOR were significantly decreased. These outcomes suggest that GLP promotes apoptosis and autophagy in hepatoblastoma cells by regulating the Akt/mTOR pathway.
Animals
;
Humans
;
Autophagy/drug effects*
;
Reishi/chemistry*
;
Mice
;
Apoptosis/drug effects*
;
TOR Serine-Threonine Kinases/genetics*
;
Proto-Oncogene Proteins c-akt/genetics*
;
Liver Neoplasms/genetics*
;
Hepatoblastoma/genetics*
;
Polysaccharides/pharmacology*
;
Cell Line, Tumor
;
Signal Transduction/drug effects*
;
Male
;
Cell Proliferation/drug effects*
;
Hep G2 Cells
7.Exploring urban versus rural disparities in atrial fibrillation: prevalence and management trends among elderly Chinese in a screening study.
Wei ZHANG ; Yi CHEN ; Lei-Xiao HU ; Jia-Hui XIA ; Xiao-Fei YE ; Wen-Yuan-Yue WANG ; Xin-Yu WANG ; Quan-Yong XIANG ; Qin TAN ; Xiao-Long WANG ; Xiao-Min YANG ; De-Chao ZHAO ; Xin CHEN ; Yan LI ; Ji-Guang WANG ; FOR THE IMPRESSION INVESTIGATORS AND COORDINATORS
Journal of Geriatric Cardiology 2025;22(2):246-254
BACKGROUND:
Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese.
METHODS:
Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics.
RESULTS:
The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05).
CONCLUSIONS
In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.
8.Integrated evidence chain-based effectiveness evaluation of traditional Chinese medicines (Eff-iEC): A demonstration study.
Ye LUO ; Xu ZHAO ; Ruilin WANG ; Xiaoyan ZHAN ; Tianyi ZHANG ; Tingting HE ; Jing JING ; Jianyu LI ; Fengyi LI ; Ping ZHANG ; Junling CAO ; Jinfa TANG ; Zhijie MA ; Tingming SHEN ; Shuanglin QIN ; Ming YANG ; Jun ZHAO ; Zhaofang BAI ; Jiabo WANG ; Aiguo DAI ; Xiangmei CHEN ; Xiaohe XIAO
Acta Pharmaceutica Sinica B 2025;15(2):909-918
Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.
9.Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study.
Yuanyue ZHU ; Linhui SHEN ; Yanan HUO ; Qin WAN ; Yingfen QIN ; Ruying HU ; Lixin SHI ; Qing SU ; Xuefeng YU ; Li YAN ; Guijun QIN ; Xulei TANG ; Gang CHEN ; Yu XU ; Tiange WANG ; Zhiyun ZHAO ; Zhengnan GAO ; Guixia WANG ; Feixia SHEN ; Xuejiang GU ; Zuojie LUO ; Li CHEN ; Qiang LI ; Zhen YE ; Yinfei ZHANG ; Chao LIU ; Youmin WANG ; Shengli WU ; Tao YANG ; Huacong DENG ; Lulu CHEN ; Tianshu ZENG ; Jiajun ZHAO ; Yiming MU ; Weiqing WANG ; Guang NING ; Jieli LU ; Min XU ; Yufang BI ; Weiguo HU
Frontiers of Medicine 2025;19(1):79-89
This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans
;
Mendelian Randomization Analysis
;
Gallstones/complications*
;
Female
;
Male
;
Cholecystectomy/statistics & numerical data*
;
Middle Aged
;
Risk Factors
;
Aged
;
Adult
;
Neoplasms/etiology*
;
Stomach Neoplasms/epidemiology*
10.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.

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