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.Comparison of esketamine versus dexmedetomidine in improving adverse mood after cesarean section
Dongmei ZHU ; Fengzhi LIU ; Ximing LI ; Xiaoyan ZHANG ; Benjuan LIU ; Lina ZHONG ; Peng XIA
Chinese Journal of Anesthesiology 2024;44(3):277-281
Objective:To compare esketamine versus dexmedetomidine in improving the adverse mood after cesarean section.Methods:One hundred and fourteen pregnant women undergoing elective cesarean section, aged 20-45 yr, with body mass index≤33 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, were divided into 3 groups ( n=38 each) by the random number table method: esketamine group (group S), dexmedetomidine group (group D) and control group (group C). After delivery, esketamine was intravenously injected as a bolus of 0.3 mg/kg, followed by an infusion of 0.3 mg·kg -1·h -1 throughout the surgery in group S, dexmedetomidine was intravenously injected as a bolus of 0.6 μg/kg, followed by an infusion of 0.6 μg·kg -1·h -1 throughout the surgery in group D, while the equal volume of normal saline was given instead, followed by an infusion of 14 ml/h throughout the surgery in group C. Patient-controlled intravenous analgesia was performed after the end of surgery. Esketamine 50 mg, sufentanil 50 μg and ondansetron 8 mg were given in group S, dexmedetomidine 200 μg, sufentanil 50 μg and ondansetron 8 mg were given in group D, while sufentanil 50 μg and ondansetron 8 mg were given in group C. When the visual analog scale score ≥4 within 48 h after operation, flurbiprofen axidate was intravenously injected as a rescue analgesic. Self-rating Anxiety Scale (SAS) scores and Edinburgh Postnatal Depression Scale (EPDS) scores were assessed at 1 day before surgery and 2 and 7 days after surgery. Serum levels of brain-derived neurotrophic factor (BDNF) were measured by enzyme-linked immunosorbent assay at 1 day before surgery and 2 days after surgery. The effective pressing times of patient-controlled analgesia (PCA) and requirement for rescue analgesia after operation were recorded. The occurrence of adverse reactions during operation and within 48 h after operation was also recorded. Results:Compared with group C, SAS scores and EPDS scores were significantly decreased at 2 and 7 days after surgery, serum BDNF concentrations were increased at 2 days after surgery, the effective pressing times of PCA were reduced, the requirement for rescue analgesia was decreased, and the incidence of intraoperative nausea and vomiting was reduced in S and D groups ( P<0.05). Compared with group D, SAS scores and EPDS scores were significantly decreased at 7 days after surgery, the effective pressing times of PCA were reduced ( P<0.05), and no significant change was found in serum BDNF concentrations at 2 days after surgery and requirement for rescue analgesia in group S ( P>0.05). The incidence of dreaminess was significantly higher in group S than in group C and group D ( P<0.05). Conclusions:Esketamine is better than dexmedetomidine in improving the adverse mood after cesarean section.
3.Study on Quality Evaluation of Notopterygii Rhizoma et Radix through UPLC Fingerprint Combined with Chemometrics Analysis and Multi Index Component Content Determination
Guangming HE ; Xiaoying LU ; Tianrui XIA ; Feifei XIE ; Rui LUO ; Weisheng LYU ; Yueyi LIANG ; Zhenyu LI ; Xiuzhi LI ; Jianxiang ZHANG ; Xiangdong CHEN ; Dongmei SUN
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(8):126-132
Objective To establish the ultra-high performance liquid chromatography(UPLC)chromatographic fingerprint of Notopterygii Rhizoma et Radix;To determine the contents of ferulic acid,nodakenin,ammijin,notopterol,isoimperatorin and volatile oil of Notopterygii Rhizoma et Radix from different producing areas;To provide reference for quality evaluation of Notopterygii Rhizoma et Radix.Methods Waters BEH C18 chromatographic column(2.1 mm×150 mm,1.7 μm)was used,with mobile phase acetonitrile-0.02%formic acid aqueous solution gradient elution,flow rate 0.25 mL/min,column temperature 25℃,detection wavelength 330 nm,injection volume 2 μL.UPLC fingerprints of 25 batches of Notopterygii Rhizoma et Radix were established,and the similarity analysis and chemometrics analysis were carried out.The contents of ferulic acid,nodakenin,ammijin,notopterol and isoimperatorin were determined simultaneously,and the contents of volatile oil was determined by steam distillation method.Results Totally 23 common fingerprint peaks were calibrated,11 known components were identified.According to the results of the cluster analysis and principal component analysis,25 batches of Notopterygii Rhizoma et Radix samples were divided into 3 categories,and the 6 potential differential components were screened out by orthogonal partial least squares-discriminant analysis(OPLS-DA).The results showed that the contents of notopterol and volatile oil from Sichuan Province were higher than those from Gansu Province and Qinghai Province.Conclusion The method established in the study is accurate and reliable,which can provide scientific basis and reference for the quality evaluation and control of Notopterygii Rhizoma et Radix.
4.Cystatin C combined with prothrombin time for assessing the condition and outcome of patients with severe fever with thrombocytopenia syndrome
Guangshun SHI ; Dongmei XIA ; Liyu ZHU
Chinese Journal of Infection and Chemotherapy 2024;24(5):553-557
Objective To investigate the value of early cystatin C(Cys-C)combined with prothrombin time(PT)for assessing the severity and outcome of patients with severe fever with thrombocytopenia syndrome(SFTS).Methods The data of 101 patients with SFTS diagnosed and treated in Chaohu Hospital of Anhui Medical University from April 2021 to August 2023 were reviewed retrospectively.The patients were assigned to non-severe group or severe group according to the severity of the disease,and assigned to survivors group or deaths group according to the treatment outcome.The clinical manifestations and early laboratory test results were compared between groups.Logistic regression model was used to analyze the factors for predicting the outcome.The receiver operating characteristic(ROC)curve was used to evaluate the ability of Cys-C and PT levels alone and in combination to distinguish survivors from deaths.Results In the early stage,the patients in severe group and deaths group showed significantly higher levels of serum Cys-C,blood urea nitrogen(BUN),creatinine(Cr),uric acid(UA),PT,activated partial thromboplastin time(APTT),creatine kinase(CK)and creatine kinase MB(CKMB)but significantly lower lymphocyte count compared to the patients in the non-severe group and survivors group(P<0.05).Multivariate binary Logistic regression analysis showed that age(OR=1.146,95%CI:1.036-1.267),PT(OR=2.643,95%CI:1.323-5.281),and Cys-C(OR=5.039,95%CI:1.548-16.395)were independent risk factors for the outcome of SFTS patients.Serum Cys-C was valuable in distinguishing survivors from deaths,the area under the ROC curve of which was 0.831.When Cys-C,PT and age were combined,the AUC was up to 0.930.Conclusions SFTS mainly occurs in farmers and elderly people.Serum PT and Cys-C levels at early stage can effectively predict the outcome of patients with SFTS.PT and Cys-C levels are expected to be biomarkers for distinguishing survivors from deaths.
5.Study on UPLC fingerprint of Mume flos at different flowering stages based on chemometrics analysis
Shuang HUANG ; Yueyi LIANG ; Jie YANG ; Weisheng LYU ; Xiaoying LU ; Guangming HE ; Zhipeng CHEN ; Xuxuan HOU ; Tianrui XIA ; Zhenyu LI ; Congyou DENG ; Xiangdong CHEN ; Dongmei SUN
International Journal of Traditional Chinese Medicine 2024;46(7):898-904
Objective:To establish the ultra high performance liquid chromatography (UPLC) fingerprints of Mume flos at different flowering stages; To provide reference for the quality research of Mume flos.Methods:The fingerprints of Mume flos were established by UPLC method, and the common peaks were identified by high performance liquid chromatography high resolution mass spectrometry (LC-MS). Chemometrics analysis was carried out with the fingerprints' common peak area of plum blossom at different flowering stages as a variable. Semiquantitative analysis of changes in flavonoids and phenolic acids in Mume flos at different flowering stages was conduct using peak area calculation method.Results:Totally 31 common peaks were identified in the fingerprints of plum blossom medicinal materials at different flowering stages and 9 components were identified. Clustering analysis (HCA) and principal component analysis (PCA) both classified plum blossom medicinal herbs at different flowering stages into three categories. Among them, there were significant differences between the groups at the bud stage, blooming period, and final flowering period, while the differences between the groups at blooming period and final flowering period were relatively small. The orthogonal partial least squares discriminant analysis (OPLS-DA) screened 16 different components with VIP>1.0. The contents of phenolic acids in different flowering stages were as follows: bud stage>blooming period>final flowering period, while the contents of flavonoids were as follows: blooming period>final flowering period>bud stage.Conclusions:This method is simple and reliable, and can provide reference for the quality evaluation of plum blossom medicinal materials at different flowering stages.
6.Analysis of serum allergen detection results in patients with allergic rhinitis in Fengtai district of Beijing
Xing XIA ; Hui JIANG ; Zitong WANG ; Dongmei WANG ; Jiaxi WANG
Chinese Journal of Clinical Laboratory Science 2024;42(9):712-717
Objective To retrospectively analyze the allergen detection results of 1 193 patients with allergic rhinitis(AR)in Fengtai district of Beijing,and provide clinical evidence for the prevention and diagnosis of AR.Methods 1 193 patients diagnosed with AR and undergone the detection of serum specific IgE against allergens at the Department of Otolaryngology,Dongfang Hospital,Beijing University of Chinese Medicine from January to December 2022 were included,and the correlations between the allergen test results and the patients'gender and age,and season were analyzed.Results Among the 1 193 patients,a total of 947 patients had positive serum allergy test results,with a positive detection rate of 79.38%.The main allergens of the AR patients in Fengtai district of Beijing were Cyperus/Birch,Artemisia,and Candida/Penicillium nodosum/Mycosphaerella/Streptomyces/Aspergillus niger.The positive rate of allergens in male AR patients(82.15%)was higher than that in females(77.23%),and the difference was statistically significant(P<0.05).The highest positive rate(85.35%)of allergens was found in autumn,and there was a statistically significant difference in the positive rates of allergens between different seasons(P<0.05).The positive rate(95.68%)of allergens was the highest in the≤14-year-old group,and there was a statistically significant difference in the positive rates of allergens among patients of different age groups(P<0.001).Conclusion The allergens of AR patients in Fengtai district of Beijing have difference and diversity,and the difference is related to gender,season and age.
7.Analysis of typical experiences of public hospital salary system reform in Sichuan province
Xiaochun ZHANG ; Dongmei XIE ; Wen CHEN ; Yi YANG ; Lei LUO ; Yashu RAO ; Xia ZHONG ; Yue HU ; Jia HE ; Jie XIAO ; Tao WU
Chinese Journal of Hospital Administration 2023;39(2):102-107
Objective:To analyze the experiences and practice in the reform of public hospital salary system in Sichuan province, summarize the typical modes of such reform in the province, and provide references for further reform.Methods:As of October 29, 2021, the research group received 77 sets of typical experience materials submitted by the health commissions and public hospitals in Sichuan province on enforcing the reform of the public hospital salary system. The analysis framework was based on the five main elements proposed in the Guidance to Deepening the Reform of the Salary System of Public Hospitals for the purpose of furthering the reform. These five elements refer to " reasonably determining the level of salary in public hospitals" " fully implementing the autonomy of internal distribution in public hospitals " " establishing and improving the incentive and restraint mechanism for the remuneration of public hospital leaders" " improving the assessment and evaluation mechanism oriented to public welfare" and " funding sources ". A quantitative analysis was made on the typical experience materials using the social network analysis method, while a qualitative analysis was made on the typical experience materials using the content analysis method. Results:The results of social network analysis showed that the network density was 0.272; the highest point centrality was " fully implement the autonomy of internal distribution in public hospitals" (0.935), and the highest intermediary centrality was " improving the assessment and evaluation mechanism oriented to public welfare" (0.870), while the closeness to centrality of " establishing and improving the incentive and constraint mechanism for the salary of public hospital leaders" (0.434) and " funding sources" (0.421) were relatively low. The results of content analysis showed that the ones with higher frequency among all the typical experience materials were " fully implementing the autonomy of internal distribution of hospitals" (72 times) and " improving the assessment and evaluation mechanism oriented to public welfare" (67 times), while the ones with lower frequency were " establishing and improving the salary incentive and constraint mechanism for public hospital leaders" (17 times) and " funding sources" (14 times). In terms of unity and synergy, the typical models of public hospital salary system reform in the province could be categorized as the fine standard mode, the fair value mode, the autonomous synergy mode and the circular symbiosis mode.Conclusions:Deepening the reform of the salary system of public hospitals should unify the standards and improve the fair and refined assessment and evaluation mechanism; explore various forms of distribution and build an internal autonomous and synergistic incentive mechanism; pay attention to the weak remuneration incentive mechanism for hospital leaders and the problem of a relatively single source of funding.
8.Research progress on the bone-marrow sparing intensity-modulated radiotherapy for cervical cancer
Jia'nan WANG ; Xi YU ; Qiuyue SU ; Dongmei LIU ; Jingqi XIA ; Shanshan YANG
Chinese Journal of Radiation Oncology 2023;32(8):731-735
The cisplatin-based concurrent chemoradiotherapy (CCRT) has been accepted as a standard treatment for most locally advanced cervical cancer. Compared with radiation therapy alone, CCRT can increase tumor control and survival rates, whereas it also can increase the incidence of acute hematological toxicity, which results in the treatment interruption or delay, and may even affect clinical efficacy and prognosis of patients. Therefore, how to reduce the incidence and severity of acute hematological toxicity induced by CCRT is a hot spot of clinical research. Previous studies have demonstrated that the occurrence of hematological toxicity is associated with the volume and dose of irradiated pelvic bone marrow. With the development of modern radiotherapy technology, precise radiotherapy technologies, such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), not only guaranteed the enough dose for tumor, but also realized the protection of normal tissues. This article will focus on the feasibility of bone marrow sparing during CCRT for cervical cancer, and summarize the research progress in recent years.
9.The role of SUMOylation in the protective mechanisms of therapeutic hypothermia on neonatal hypoxic-ischemic encephalopathy
Xiaozhi LIU ; Panpan XU ; Chunyan ZHANG ; Xia GAO ; Guangbi LIU ; Dongmei CHU ; Yang LIU ; Xiuying TIAN ; Jun ZHENG
Chinese Journal of Neonatology 2023;38(5):294-300
Objective:To study the role of SUMOylation in the process of therapeutic hypothermia on neural stem cells (NSCs) in neonatal hypoxic-ischemic encephalopathy.Methods:SUMOylation is an essential post-translational modification involving small ubiquitin-like modifiers (SUMOs). Primary-cultured NSCs from mice were assigned into four groups: control group, hypoxia group, hypothermia group and hypoxia+hypothermia group. Western Blot was used to detect the protein levels of SUMO2/3, hypoxia-inducible factor-1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator factor 1α (PGC-1α) and octamer binding transcription factor 4 (Oct4). The diameters of NSCs were compared. ELISA was used to detect lactate dehydrogenase (LDH) level. Apoptosis was examined using flow cytometry. Immunofluorescence method was used to measure the differentiation of NSCs into neuronal cells.Results:Compared with the control group, the levels of SUMO2/3, HIF-1αand PGC-1α in NSCs of the hypoxia group increased 33%, 126% and 140%, respectively ( P<0.05). Compared with the control group, the levels of SUMO2/3 and PGC-1α in NSCs of the hypothermia group increased 52% and 536%, respectively ( P<0.05). Compared with the hypoxia group, the levels of SUMO2/3, HIF-1α, PGC-1α and Oct4 in the hypoxia+hypothermia group increased 44%, 40%, 230% and 59%, respectively ( P<0.05). The diameters of NSCs in hypoxia group, hypothermia group and hypoxia+hypothermia group were smaller than control group, and hypoxia+hypothermia group smaller than hypoxia group ( P<0.05). No significant differences existed in LDH levels between hypothermia group and control group ( P>0.05). LDH level in hypoxia+hypothermia group were significantly lower than hypoxia group ( P<0.05). No significant differences existed in the cell death rates between hypothermia group and control group ( P>0.05). The cell death rate in hypoxia+hypothermia group was significantly lower than hypoxia group ( P<0.05). Compared with the control group, the expressions of Nestin in both hypoxia group and hypothermia group were increased, but neuron specific enolase (NSE) were decreased ( P<0.05). Compared with hypoxia group and hypothermia group, the level of Nestin in hypoxia+hypothermia group was further increased, while NSE was further decreased ( P<0.05). Conclusions:Therapeutic hypothermia may increase the tolerance of NSCs to hypoxia by enhancing SUMO modification of proteins, providing theoretical basis for the treatment of hypoxic-ischemic encephalopathy with therapeutic hypothermia.
10.Retrospective analysis of HIV infection among blood donors in Beijing Area from 1994 to 2021
Dong ZHANG ; Xiaoyan GONG ; Dongmei CHEN ; Hongyin XIA ; Zhuoyan WANG ; Yan QIU ; Li CHEN
Chinese Journal of Experimental and Clinical Virology 2023;37(4):377-382
Objective:To understand the status of human immunodeficiency virus (HIV)infection among blood donors in Beijing from 1994 to 2021, analyze the prevalence characteristics and influencing factors of HIV infection among blood donors, and provide reference for blood donor management and blood safety assurance.Methods:Using descriptive epidemiological method to analyze the situation of HIV enzyme-linked immunosorbent assay (ELISA) combined with nucleic acid detection (NAT), third-party confirmatory laboratory test western blot (WB) result and basic demographic information of infected patients among blood donors.Results:From 1994 to 2021, a total of 6 450 244 person-times participated in blood donation, of which 7 622 were reactive in the primary screening, and 1 553 were positive after the HIV confirmation test, average detection rate is (2.14 per 10 000), the vary of detection rates were statistically significant from year to year( χ2=899.690, P<0.01), with the highest detection rate in 2015 (5.93 per 10 000) and the lowest in 1994 (0). From 2011 to 2021, 3 802 primary screening reactive specimens detected by ELISA combined with NAT were confirmed by WB test, of which 1 191 were positive in the confirmatory test, all of which were ELISA seropositive, of which 682 were NAT (+ ). The gender distribution of the infected population is mainly male (95.30%); the age distribution is mainly 18-30 years old (62.40%); in terms of occupation, the detection rate of infected people is higher among employees, workers and others (including unknown), accounting for 83.26% of the total number of infected persons. The ABO blood group system was dominated by A, B and O (89.7%) and the Rh blood group system was dominated by Rh-positive (99.25%); the detection rate of infection was higher among first-time donors than repeat donors ( χ2=39.587, P<0.01). Conclusions:From 1994 to 2021, the annual number of HIV-infected blood donors in Beijing was greatly affected by the external environment. Although the current screening strategy can reasonably shield HIV-infected people, the detection rate of HIV-infected people in this area is relatively high. In view of the different characteristics of HIV-infected people, follow-up treatment plans should be made to ensure blood safety.

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