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.Study on Colorimetric Sensor Array Based on Enzymatic Method for Highly Selective Detection of Sarin
Lian-Bo JIANG ; Guo-Hong LIU ; Zhuang-Hu XU ; Jian LI ; Yong-Ling SHEN ; Cai-Xia XU ; Chuan-Qin ZANG ; Yan-Hua XIAO ; Dan-Ping LI ; Ting LIANG
Chinese Journal of Analytical Chemistry 2025;53(5):832-841,中插21-中插23
Sarin(GB)is a typical representative of nerve agents with high toxicity,and very low amount can cause death.GB can cause water and atmospheric environment poisoning,so the detection of GB in water and air is of great significance.In this work,a colorimetric sensor array(CSA)based on GB inhibition of cholinesterase activity was constructed to detect GB with high selectivity.A 4×4 colorimetric array was constructed using acetylcholinesterase(AChE),butyryl cholinesterase(BuChE)and the corresponding substrate acetylthiocholine iodide(S-ACh),butyryl thiocholine iodide(S-BCh),acetylcholine chloride(ACh),butyryl choline chloride(BCh)and 2,6-dichloroindophenol ethyl ester(DCIE).The linear curve of the sensor was Y=131.3×lgC+271.6(R2=0.997),where Y was the array response Euclidean distance,C was the concentration of GB(mg/L),the linear range was 0.03?0.32 mg/L,and the detection limit was 27.6 μg/L.The method could effectively distinguish chemical warfare agents(CWA)such as VX,Soman(GD),mustard gas(HD),Louie reagent(L),and had high anti-interference ability,sensitivity and good repeatability.It was successfully applied to the detection of GB in simulated water and simulated air samples,and the sample recovery rate was 97.2% ?100.9%.This method would be potentially applied to the field rapid detection of nerve agents.
3.Expert consensus on visualized tele-round and quality control management based on the improvement of clinical practice ability
Wanhong YIN ; Xiaoting WANG ; Ran ZHOU ; Dawei LIU ; Yan KANG ; Yaoqing TANG ; Xiaochun MA ; Jianguo LI ; Zhenjie HU ; Haitao ZHANG ; Wei HE ; Lixia LIU ; Wenjin CHEN ; Ran ZHU ; Jun WU ; Hongmin ZHANG ; Lina ZHANG ; Wenzhao CHAI ; Shihong ZHU ; Wangbin XU ; Rongqing SUN ; Xiangyou YU ; Tianjiao SONG ; Ying ZHU ; Hong REN ; Ai SHANMU ; Qing ZHANG ; Wei FANG ; Xiuling SHANG ; Liwen LYU ; Shuhan CAI ; Xin DING ; Heng ZHANG ; Guang FENG ; Lipeng ZHANG ; Bo HU ; Dong ZHANG ; Weidong WU ; Feng SHEN ; Xiaojun YANG ; Zhenguo ZENG ; Qibing HUANG ; Xueying ZENG ; Tongjuan ZOU ; Milin PENG ; Yulong YAO ; Mingming CHEN ; Hui LIAN ; Jingmei WANG ; Yong LI ; Feng QU ; Gang YE ; Rongli YANG ; Xiukai CHEN ; Suwei LI ; Juxiang WANG ; Yangong CHAO
Chinese Journal of Internal Medicine 2025;64(2):101-109
Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.
4.Effects of different hemostatic devices on safety and comfort of compression hemostasis in patients after transradial coronary intervention
Yan-ling XU ; Lian-sheng WANG ; Dong-mei SHI
Chinese Medical Equipment Journal 2025;46(1):49-54
Objective To investigate the effects of different hemostatic devices on the safety and comfort of compression hemostasis in the patients undergoing transradial coronary intervention(TRI).Methods From March to September 2023,900 patients undergoing TRI in the cardiology department of some hospital were divided into three groups according to the randomized numerical table method:STEPTY P hemostatic patch group(group A),spinning hemostatic group(group B)and balloon hemostatic group(group C),with 300 cases in each group.The three groups were compared in terms of the hemostatic effect,local complications and comfort of the puncture sites.Results The three groups had no statistical differences in hematoma grade and incidence rates of hematoma and hemorrhage(all P>0.05).There were significant differences in the occurrence of skin injury among the three groups(P=0.011),and group A had the skin injury incidence rate(1.0%)statistically lower than those of group B(4.3%)and C(5.3%)(P<0.05).There were obvious differences among the three groups in the incidence rates of pain on the operative side,palm swelling and limb numbness(P<0.05),and group A had the incidence rates significantly lower than those of group B and C(all P<0.05).Conclusion All the three compression hemostatic devices can achieve safe and effective post-TRI hemostasis.When compared with the other two devices,STEPTY P hemostatic patch is more effective in reducing the probability of related complications and improving patient comfort while effectively compressing the puncture site for hemostasis.[Chinese Medical Equipment Journal,2025,46(1):49-54]
5.Alpha-synuclein Fibrils Inhibit Activation of the BDNF/ERK Signaling Loop in the mPFC to Induce Parkinson's Disease-like Alterations with Depression.
Zhuoran MA ; Yan XU ; Piaopiao LIAN ; Yi WU ; Ke LIU ; Zhaoyuan ZHANG ; Zhicheng TANG ; Xiaoman YANG ; Xuebing CAO
Neuroscience Bulletin 2025;41(6):951-969
Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals
;
Brain-Derived Neurotrophic Factor/metabolism*
;
alpha-Synuclein/metabolism*
;
Male
;
Prefrontal Cortex/drug effects*
;
Rats, Sprague-Dawley
;
Depression/metabolism*
;
MAP Kinase Signaling System/drug effects*
;
Rats
;
Parkinson Disease/metabolism*
;
Receptor, trkB/metabolism*
;
Phosphorylation
;
Disease Models, Animal
;
Signal Transduction
6.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.
7.Microwave imaging method based on deep convolutional autoencoder and its potential for medical application
Huangsen DENG ; Jie LIU ; Lian YAN ; Guangzheng ZHU ; Xu NING ; Mingxin QIN ; Mingsheng CHEN
Chinese Journal of Medical Physics 2025;42(2):184-189
A deep learning based microwave imaging model which can directly map the scattered electric field to the dielectric property distribution image of the target object is developed,and its potential for medical applications is explored.The two-dimensional time-domain finite difference method is used for numerical simulation to obtain a dataset of scattered electric fields;a deep convolutional autoencoder based imaging model is constructed to perform imaging studies on two types of target objects;the imaging results are quantitatively evaluated using relative error,and the model's ability to distinguish different types of strokes is also analyzed.The results show that the imaging network based on deep convolutional autoencoder exhibits excellent imaging performance when processing both numerical models.For simple objects,the model can accurately locate and preliminarily reconstruct the shape of the object,with an average relative error of 0.3012,while for the stroke models,it can effectively reconstruct the location and shape of the stroke area,and preliminarily reconstruct other brain tissues,with an average relative error of 0.077 8.The microwave imaging network based on deep convolutional autoencoder has great promise for fast and accurate image reconstruction,and the numerical example of stroke detection demonstrates its significant application potential in biomedical imaging.
8.Clinical Study of Modified Cangfu Daotan Decoction Combined with Ethinylestradiol and Cyproterone Acetate,Metformin in Patients with Spleen Deficiency Phlegm-Dampness Type Polycystic Ovary Syndrome Accompanied by Insulin Resistance
Jing LIN ; Fan CHEN ; Yan-hua CHEN ; Ying XU ; Lin-lin WANG ; Hong WANG ; Xi-na LIAN ; Rong-qian XU
Progress in Modern Biomedicine 2025;25(17):2768-2775,2739
Objective:To observe the clinical effect of Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type polycystic ovary syndrome(PCOS)accompanied by insulin resistance.Methods:80 patients with PCOS accompanied by insulin resistance who were admitted to our hospital from June 2023 to June 2024 were included.The patients were divided into control group(treated with ethinylestradiol and cyproterone acetate,metformin)and study group(treated with modified Cangfu Daotan Decoction combine with ethinylestradiol and cyproterone acetate,metformin)by the random number table method,with 40 cases in each group.The total clinical effective rate,TCM syndrome score,sex hormone levels[prolactin(PRL),estradiol(E2),follicle-stimulating hormone(FSH),testosterone(T),and luteinizing hormone(LH)],insulin resistance indicators[fasting insulin(FINS),fasting blood glucose(FBG),homeostatic model assessment of insulin resistance(HOMA-IR)],and endometrial receptivity[pulsatile index(PI),resistance index(RI),endometrial thickness(ET),ovulation rate]and the occurrence of adverse reactions were compared between the two groups.Results:Compared with the control group after treatment,the total clinical effective rate,PRL,E2,FSH level,ET and the ovulation ratein the study group were higher,while the main symptoms,secondary symptoms,total score,T,LH levels,FBG,FINS levels,HOMA-IR,PI and RI were lower(P<0.05).There was no difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type PCOS accompanied by insulin resistance,can improve the clinical symptoms,increase the total clinical effective rate,it may be related to the regulation of insulin resistance,sex hormone levels,and endometrial receptivity,it is safe and reliable.
9.A Mouse Model of Polycystic Ovary Syndrome Established Through Subcutaneous Administration of Letrozole Sustained-Release Pellets and Hepatic Transcriptome Analysis
Qiuyu XU ; Guofeng YAN ; Li FU ; Wenhua FAN ; Jing ZHOU ; Lian ZHU ; Shuwen QIU ; Jie ZHANG ; Ling WU
Laboratory Animal and Comparative Medicine 2025;45(2):119-129
Objective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome(PCOS).The liver transcriptomes of the model mice are compared with those of the placebo control mice to investigate the underlying mechanisms of liver involvement in the pathogenesis of PCOS.Methods A customized 2 mg dose of letrozole sustained-release pellets with a 40-day release period was used.The control placebo and letrozole pellets were implanted subcutaneously in the dorsal cervical region of 3-4-week-old C57BL/6J mice(8 mice per group)to establish the control group and letrozole-induced PCOS model group.Both groups were treated with a high-fat diet starting the day after administration.The modeling period lasted for 5 weeks,during which body weight and 24-hour food intake were monitored in each group every week.When samples were collected,liver weight was recorded.Pathological changes in ovarian and hepatic tissues were examined by hematoxylin-eosin(HE)staining,while hepatic lipid deposition was observed by Oil Red O staining.The extent of macrophage infiltration in the liver was evaluated via F4/80 immunohistochemical staining,and hepatic fibrosis levels were observed by Masson's trichrome staining.Transcriptomic sequencing was performed to analyze differentially expressed genes(DEGs)in liver tissues between the control and model groups,followed by enrichment analysis of significant DEGs.Quantitative real-time fluorescent quantitative PCR(qPCR)was subsequently used to validate the expression of significant DEGs in liver tissues of both groups.Results Compared with the control group,the model group which received subcutaneous letrozole sustained-release pellets combined with a high-fat diet exhibited significantly increased body weight(P<0.001),prominent polycystic ovarian morphology,and significantly decreased liver-to-body weight ratio(P<0.05).However,no significant changes were observed in absolute liver weight(P>0.05),hepatic histomorphology,or lipid deposition.Transcriptome sequencing identified 119 upregulated and 217 downregulated DEGs in the liver tissues of letrozole-treated mice,which were predominantly enriched in pathways related to cholesterol and steroid biosynthesis,steroid hormone metabolism,and inflammatory responses.qPCR validation demonstrated that mRNA expression of HSD3B2 and HMGCR was significantly upregulated in liver(P<0.01),while mRNA expression of IL4,CCL2 and COL1A1 was downregulated(P<0.05)in the model group compared with the control group.However,Masson's trichrome staining and F4/80 immunohistochemical analysis showed no significant changes in hepatic fibrosis or macrophage infiltration.Conclusion Subcutaneous administration of letrozole sustained-release pellets combined with a high-fat diet successfully establishes a mouse model of PCOS.The model mice exhibited significant changes in hepatic gene expression.Liver may contribute to PCOS pathogenesis through regulating cholesterol and steroid metabolism.
10.Clinical Study of Modified Cangfu Daotan Decoction Combined with Ethinylestradiol and Cyproterone Acetate,Metformin in Patients with Spleen Deficiency Phlegm-Dampness Type Polycystic Ovary Syndrome Accompanied by Insulin Resistance
Jing LIN ; Fan CHEN ; Yan-hua CHEN ; Ying XU ; Lin-lin WANG ; Hong WANG ; Xi-na LIAN ; Rong-qian XU
Progress in Modern Biomedicine 2025;25(17):2768-2775,2739
Objective:To observe the clinical effect of Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type polycystic ovary syndrome(PCOS)accompanied by insulin resistance.Methods:80 patients with PCOS accompanied by insulin resistance who were admitted to our hospital from June 2023 to June 2024 were included.The patients were divided into control group(treated with ethinylestradiol and cyproterone acetate,metformin)and study group(treated with modified Cangfu Daotan Decoction combine with ethinylestradiol and cyproterone acetate,metformin)by the random number table method,with 40 cases in each group.The total clinical effective rate,TCM syndrome score,sex hormone levels[prolactin(PRL),estradiol(E2),follicle-stimulating hormone(FSH),testosterone(T),and luteinizing hormone(LH)],insulin resistance indicators[fasting insulin(FINS),fasting blood glucose(FBG),homeostatic model assessment of insulin resistance(HOMA-IR)],and endometrial receptivity[pulsatile index(PI),resistance index(RI),endometrial thickness(ET),ovulation rate]and the occurrence of adverse reactions were compared between the two groups.Results:Compared with the control group after treatment,the total clinical effective rate,PRL,E2,FSH level,ET and the ovulation ratein the study group were higher,while the main symptoms,secondary symptoms,total score,T,LH levels,FBG,FINS levels,HOMA-IR,PI and RI were lower(P<0.05).There was no difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type PCOS accompanied by insulin resistance,can improve the clinical symptoms,increase the total clinical effective rate,it may be related to the regulation of insulin resistance,sex hormone levels,and endometrial receptivity,it is safe and reliable.

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