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.Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway in vivo and in vitro.
Fen ZHANG ; Lanlan XIAO ; Ya YANG ; Menghao ZHOU ; Yalei ZHAO ; Zhongyang XIE ; Xiaoxi OUYANG ; Feiyang JI ; Shima TANG ; Lanjuan LI
Frontiers of Medicine 2023;17(3):534-548
Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.
Mice
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Animals
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Humans
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Hepatitis, Autoimmune/pathology*
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Signal Transduction
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Disease Models, Animal
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Stem Cells
3.Fluid management strategies for patients with severe blast injury
Minfei YANG ; Mengyun XU ; Yu KE ; Xiao LU ; Lanlan ZHANG ; Xiaoyue YAO
Chinese Journal of Practical Nursing 2023;39(14):1105-1109
Objective:To summarize the precision fluid management of patients with severe blast injury in the emergency intensive care unit, so as to help patients smoothly pass through the dangerous period and recover smoothly.Methods:Based on the experience of fluid management in 6 patients admitted to the Second Affiliated Hospital Zhejiang University School of Medicine in the tanker truck explosion on 14 June, 2020. The main measures included: fluid volume management and dynamic adjustment; assessment of intake, output and urine volume, and dynamic adjustment of infusion volume and speed; monitoring of pulmonary oxygenation and timely adjustment of fluid resuscitation strategies; monitoring indexes and providing nursing care strategies for fluid management.Results:Finally, among 6 patients with severe blast injury, 5 patients were discharged from the hospital with follow-up treatment after they suffered from the shock and infection phases and refined fluid management, 1 patient died due to severe injury and ineffective rescue.Conclusions:Adopting individualized, phased, and refined liquid management strategy has clinical significance for patients with severe blast injury to smoothly pass the risk period.
4.Prenatal diagnosis of a fetus with harlequin ichthyosis caused by novel splice-site mutation in ABCA12 gene
Juan LI ; Ling LIU ; Haiyu LI ; Yujie TAN ; Hao WANG ; Jing LI ; Yunxiao ZHI ; Xiao HAN ; Lanlan ZHAO ; Jing WANG
Chinese Journal of Perinatal Medicine 2022;25(12):958-961
This article reported a rare case of harlequin ichthyosis which was indicated with multiple structural abnormalities by prenatal ultrasound and diagnosed by trio-based whole-exome sequencing (Trio-WES). Prenatal diagnosis was performed because the ultrasound at 24 +4 gestational weeks revealed the fetus presenting with eclabium, flattened nose, short mandible, small auricle and abnormal posture of the toes. Copy number variation sequencing (CNV-seq) showed no chromosome aneuploidy or pathogenic copy number variants over 100 kb in the fetal or parental samples. Trio-WES showed that the fetus carried two heterozygous mutations, c.2593-1G>A and c.7444C>T in ABCA12. Sanger sequencing confirmed that c.2593-1G>A, a previously unreported variant, was paternally inherited and c.7444C>T was maternally inherited. Both parents had normal phenotype. The fetus was finally diagnosed with harlequin ichthyosis. After prenatal counseling, the parents made an informed choice to terminate the pregnancy at 28 +4 gestational weeks. The stillborn fetus showed multiple malformations The variants in this case expand the spectrum of variants in ABCA12 gene.
5.Analysis of vitamin D nutritional status among children aged 0 to 12 years in Chongqing
WANG Xu, LIU Xia, ZHU Lanlan, DENG Yu, XIAO Xiang, LIU Yong, LIU Feng
Chinese Journal of School Health 2022;43(11):1638-1641
Objective:
To investigate the nutritional status and associated factors of vitamin D among children aged 0 to 12 years old in Chongqing.
Methods:
From January 2019 to December 2021, 1 877 children aged 0-6 years who received regular child health care were randomly selected from Chongqing maternal and child health hospital, and 707 school age children were also selected from three primary school in Chongqing for investigation. The serum sample were collected for detecting serum 25 (OH) D level by chemiluminescence method, and the possible influencing factors of vitamin D deficiency (VDD) were analyzed.
Results:
The average serum 25 (OH) D concentration of children was (39.9±9.1) ng/mL with the positive rate of VDD was 14.59%. There were significant differences of VDD positive rate in different age, visiting time, visiting season, body shape, outdoor activity time and vitamin D supplementation (0-3 years old vs 4-6 years old vs 7-12 years old: 14.73% vs 22.19% vs 10.47%; visiting season: spring vs summer vs autumn vs winter: 12.97% vs 10.65% vs 14.86% vs 21.33%; pre COVID 19 epidemic vs post COVID-19 epidemic: 11.18% vs 17.08%; underweight or normal vs overweight or obesity: 12.34% vs 26.13%; adequate outdoor activity time vs inadequate:11.84% vs 16.27%; regular vitamin D supplementation vs irregular vitamin D supplementation: 11.71% vs 15.62% )( χ 2=26.17, 17.59, 30.98, 53.74, 9.60, 6.17, P <0.05). Underweight or normal body weight, sufficient outdoor activities and regular vitamin D supplementation were associated with less vitamin D deficiency with OR(OR95%CI ) at 0.68(0.55-0.84), 0.57 (0.25-0.77) and 0.62(0.44-0.85)( P <0.05).
Conclusion
The prevalence of VDD among preschool and school age children is high in Chongqing. Integrated prevention and control strategies incluing overweight or obesity control, increasing outdoor activities and oral vitamin D supplements should be taken.
6.The relationship study on alexithymia and interoception in patents with panic disorder
Hui LI ; Jiaoyan PANG ; Qiang HU ; Lanlan ZHANG ; Huiru CUI ; Chunbo LI ; Zeping XIAO
Chinese Journal of Behavioral Medicine and Brain Science 2019;28(7):631-635
Objective To explore the characteristics of alexithymia and interoception in patients with panic disorder(PD) and its relationship. Methods Thirty-seven patients with PD and 45 healthy con-trols who met the diagnostic criteria of DSM-Ⅳ were selected. Toronto Alexithymia Scale ( TAS) and state-trait anxiety inventory ( STAI) were used to assess the characteristics of alexithymia and anxiety symptoms respectively. The heartbeat perception levels were tested by the Mental Tracking Paradigm. Results The de-tection rate of alexithymia in patients with panic disorder was 37. 83% (14/37),but the rate in the normal control group was only 4. 44%(2/45),and the difference was statistically significant (χ2=14. 42,P<0. 05). The total score of TAS (55. 11±10. 99),factor Ⅰ (20. 62±6. 78) and factor Ⅱ (14. 68±3. 70) in the PD group were higher than those in the control group (42. 93± 9. 25,12. 82± 4. 99,11. 42±3. 04; F=20. 72, 31. 08,15. 31,P<0. 01). The levels of the heartbeat perception were higher in the PD group than that in the control group (0. 75±0. 15,0. 58±0. 19;t=4. 13,P<0. 05). In PD group,the score of STAI were positively correlated with TAS total score and factor Ⅰ and Ⅱ scores( r=0. 57,0. 61,0. 47;r=0. 54,0. 62,0. 39,P<0. 05). There was no significant correlation between the scores of STAI and the level of interoception. The mediating effect of interoception level on alexithymia and state anxiety was not significant while the mediating effect on alexithymia and trait anxiety was also not significant. Conclusions The alexithymia detection rate and interoception sensitivity in patients with panic disorder were higher than those of healthy people. There may be interaction between alexithymia and anxiety symptoms. Interoception may be a clinical feature of panic disorder.
7.Recent progress in advanced glycation end-products of gestational diabetes mellitus
Shiyu LIU ; Jiaxin FU ; Yibo MENG ; Lanlan PENG ; Hui CHEN ; Xue XIAO ; Yuan YAO
Chinese Journal of Endocrine Surgery 2018;12(4):345-347,352
Advanced glycation end-products (AGEs) are stable and toxic by-products of non-enzymatic metabolic reaction of proteins,lipids and nucleotides.The elevated serum AGEs level in pregnant women is strongly associated with hyperglycemia,oxidative stress and insulin resistance and may be one of the cause for the onset and development of the gestational diabetes mellitus(GDM).This review mainly focuses on the pathogenesis of AGEs and GDM.
8.Quality Standard of Fengshi Bitong Capsule
Mutu HUANG ; Lanlan LIN ; Xinmin XIE ; Junfeng XIAO ; Liping HAN
Herald of Medicine 2017;36(7):786-789
Objective To establish the quality standard of Fengshi Bitong Capsule.Methods Notopterygh Rhizoma,Angelicae Pubescentis,and Saposhnikoviae Radix were identified by thin layer chromatography(TLC).Aconitine limit test in this drug also carried out by TLC.The contents of Isoimperatorin in the Notopterygh Rhizoma were determined by high performance liquid chromatography(HPLC).Results The spots in the TLC were fairly clear and no interference was shown in the blank samples.The aconitine limited in conformity with the 《Chinese Pharmacopoeia》 2010.Isoimperatorin showed a good linear relationship within a range of 3.668 96-183.448 00 μg· mL-1(r=1).The average of recovery was 96.42%,RSD=2.64%,respectively.Conclusion The established methods are highly specific,stable and reproducible,which can be used as quality control of fengshi bitong capsule.
9.Correlation between non-technical skills and social support of undergraduate nursing students
Juan XIAO ; Qiongshu CHEN ; Lanlan XU
Chinese Journal of Modern Nursing 2017;23(4):566-570
Objective To investigate the correlation between non-technical skills and social support of undergraduate nursing students,and provide references for nursing educators to improve the social support and enhance the non-technical skills of nursing students.Methods Using cluster sampling method,totally 180 nursing students were investigated before clinical practice with non-technical skills inventory and social support scale by cluster sampling method from June 2016. Statistical description and correlation analysis were used to analyze the data in this study.Results There were 170 effective questionnaires,and the non-technical skills of nursing students was at middle level with score (3.570±0.419);the social support was at middle level with score (34.220±5.918). There was positive correlation between non-technical skill and social support of nursing students (r=0.181-0.294,P< 0.05). Multiple regression analysis showed that,12.8% of non-technical skills of nursing students could be explained by social support.Conclusions Social support has positive prediction to non-technical skills of nursing students. Change the social support is an effective way to improve the nursing students' non-technical skills.
10.Correlation between self-directed learning readiness and mental resilience of undergraduate nursing students
Lanlan XU ; Yan LI ; Ping LI ; Juan XIAO
Chinese Journal of Modern Nursing 2016;22(6):856-860
Objective To investigate the correlation between self-directed learning readiness and mental resilience of undergraduate nursing students, and provide reference for nursing educator to improve the psychological control source and enhance the autonomous learning ability and mental resilience of undergraduate nursing students. Methods Cluster sampling method and questionnaire survey were used in 193 nursing students from grade 2012 nursing undergraduate students. Used Self-directed Learning Readiness ( SDLR) and Connor-Davidson mental resilience scale, statistical description and correlation analysis were used to analyze the data in this study. Results There were 185 effective questionnaires, and the self-directed learning readiness of undergraduate nursing students was at middle level with score (158. 33 ± 18. 02);the locus of mental resilience was at middle level which score was (72. 67 ± 11. 64); there was positive correlation between self-directed learning readiness and mental resilience of nursing students (r =0. 204-0. 463,P <0. 01). 23. 1% of self-directed learning readiness of nursing students could explain by mental resilience. Conclusions Mental resilience has positive prediction to self-directed learning readiness of nursing students and can enhance the mental resilience, especially to cultivate the quality of self-reliance and have a positive effect on their independent learning ability.mental resilience of undergraduate nursing students, and provide reference for nursing educator to improve the psychological control source and enhance the autonomous learning ability and mental resilience of undergraduate nursing students. Methods Cluster sampling method and questionnaire survey were used in 193 nursing students from grade 2012 nursing undergraduate students. Used Self-directed Learning Readiness ( SDLR) and Connor-Davidson mental resilience scale, statistical description and correlation analysis were used to analyze the data in this study. Results There were 185 effective questionnaires, and the self-directed learning readiness of undergraduate nursing students was at middle level with score (158. 33 ± 18. 02);the locus of mental resilience was at middle level which score was (72. 67 ± 11. 64); there was positive correlation between self-directed learning readiness and mental resilience of nursing students (r =0. 204-0. 463,P <0. 01). 23. 1% of self-directed learning readiness of nursing students could explain by mental resilience. Conclusions Mental resilience has positive prediction to self-directed learning readiness of nursing students and can enhance the mental resilience, especially to cultivate the quality of self-reliance and have a positive effect on their independent learning ability.


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