1.Mechanism related to bile acids metabolism of liver injury induced by long-term administration of emodin.
Jing-Zhuo TIAN ; Lian-Mei WANG ; Yan YI ; Zhong XIAN ; Nuo DENG ; Yong ZHAO ; Chun-Ying LI ; Yu-Shi ZHANG ; Su-Yan LIU ; Jia-Yin HAN ; Chen PAN ; Chen-Yue LIU ; Jing MENG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(11):3079-3087
Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage*
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Bile Acids and Salts/metabolism*
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Animals
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Male
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Liver/injuries*
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Chemical and Drug Induced Liver Injury/genetics*
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Drugs, Chinese Herbal/adverse effects*
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Humans
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Rats, Sprague-Dawley
;
Mice
;
Rats
2.The role of Gas6/MerTK/GPX4 signal pathway in iron-induced cell death in diabetic retinopathy
Li DENG ; Ling LI ; Jiang YUE ; Zhengqun LIU ; Juanping YIN ; Xiaoli CAI
Acta Universitatis Medicinalis Anhui 2024;59(10):1777-1784
Objective To investigate the role of growth arrest-specific 6(Gas6)/Mer tyrosine kinase(MerTK)signaling pathway in ferroptosis in diabetes retinopathy(DR).Methods Human retinal pigment epithelial cells(ARPE-19)were divided into control group,HG group,HG+sh-Gas6 group,and HG+Gas6 group.Cells were exposed to 25 mmol/L D-glucose for simulating an in vitro hyperglycemic(HG)environment.The control group was exposed to a 20 mmol/L mannitol+5.5 mmol/L glucose environment.Rats were randomly divided into normal control group,DR group,and DR+Gas6 group,with 20 rats in each group.A DR model was established by intra-peritoneal injection of STZ solution.Cell proliferation was evaluated using the cell count kit 8(CCK-8)assay.Lip-id reactive oxygen species(ROS)levels were measured by flow cytometry,and levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)were measured by biochemical assays to eval-uate iron death.The expression of Gas6 and MerTK proteins was analyzed by Western blot.Results Compared with HG group,the cell viability,SOD,GSH-Px levels in HG+Gas6 group increased significantly(P<0.05),while the levels of lipid-ROS and MDA decreased significantly(P<0.05).In HG+sh-Gas6 group,the cell via-bility,SOD and GSH-Px levels decreased significantly(P<0.05),while the levels of lipid-ROS and MDA in-creased significantly(P<0.05).In addition,the expression of GPX4 protein in HG+Gas6 group was significant-ly higher than that in HG group(P<0.05),and the expression of GPX4 protein in HG+sh-Gas6 group was sig-nificantly lower than that in HG group(P<0.05).Compared with the control group,the average thickness of reti-nal nerve fiber layer in DR group significantly decreased(P<0.05),while that in DR+Gas6 group increased sig-nificantly(P<0.05).In addition,the levels of MDA and iron in retinal pigment epithelium(RPE)tissues of DR+Gas6 group decreased significantly(P<0.05),while the levels of GSH and the expressions of Gas6,MerTK and GPX4 proteins increased significantly(P<0.05).Conclusion HG treatment accelerates the clearance of GPX4 by inhibiting the Gas6/MerTK signaling pathway,inducing ferroptosis and cell growth inhibition in ARPE-19 cells.In addition,up-regulating the expression of Gas6/MerTK signal in DR rat retina can alleviate ferroptosis and oxidative stress in RPE tissue,and help to restore the average retinal nerve fiber layer thickness.
3.Scholars'consensus on the construction and development of chinese medical humanities:summary of"seminar on the construction of Chinese medical humanities"held in Harbin in August 2023
Jinfan WANG ; Mei YIN ; Yue WANG ; Huan LIU ; Zhong HE ; Yunzhang LIU ; Rui DENG ; Min CHEN ; Junrong LIU ; Yongfu CAO ; Donghong WANG ; Hongjiang ZHANG ; Fengxiang LU ; Yu CHENG ; Yuan HE ; Fang SHAN
Chinese Medical Ethics 2024;37(2):248-252
On August 2-4,2023,the"Third Summit Forum on'Building a Community of Shared Future for Doctors and Patients'"was jointly organized by institutions such as the Chinese Medical Ethics,the Hospital Humanities Management and Talent Training Special Committee of the China Population and Culture Promotion Association,Center for Ethical Studies of Renmin University of China,the Newspaper for China's Physicians,the China Health Law Society,the China Anti-Cancer Association,and the China Association For Ethical Studies in Harbin.The conference arranged a sub-forum for the"Seminar on the Construction of Chinese Medical Humanities",with domestic medical humanities scholars attending the conference.After heated discussions at the seminar,the Scholars'Consensus on the Construction and Development of Chinese Medical Humanities was formed.It was proposed that in the new era,it is urgent to build the medical humanities discipline,as well as lead the academic integration and development of medical humanities under the core socialist values.At the same time,for the construction of the medical humanities discipline,it is necessary to optimize the organizational mechanism,prosper and develop the overall framework of the medical humanities discipline,accelerate the construction of a professional teaching team for the medical humanities discipline,promote the establishment of a new carrier medical humanities education and teaching in cultivating morality and nurturing talents,as well as focus on solving problems related to the cultivation of medical humanities graduate students.
4.Evaluation of Burosumab in the treatment of X-linked hypophosphatemic rickets in children
Shaohan FANG ; Fang DENG ; Yue YUAN ; Xu LI ; Zhen ZHAO ; Ying ZHU ; Yin PENG ; Luodan ZHANG
Chinese Journal of Endocrinology and Metabolism 2024;40(1):11-16
Objective:To evaluate the efficacy and safety of Burosumab in patients with X-linked hypophosphatemic rickets.Methods:Clinical data of 9 children diagnosed with X-linked hypophosphatemic rickets and treated with Burosumab in the Department of Pediatric Nephrology, Anhui Children′s Hospital from November 2021 to September 2023 were retrospectively analyzed, including the general information, clinical manifestations, auxiliary examination, Burosumab treatment and follow-up.Results:Among the 9 cases, there were 5 males and 4 females, with a median age at diagonosis of 2 years. After traditional treatment, the fluctuation of serum phosphorus ranged from 0.7 to 0.9 mmol/L. The median age at the initiation of Burosumab treatment was 2.8 years, and the initial dosage was 0.8 mg/kg, administrated subcutaneously every 2 weeks. The laboratory and imaging indexes were improved after 6 months of Burosumab treatment, and the mean serum phosphorus level increased from(0.81±0.14) mmol/L to(1.02±0.10) mmol/L at 1 month( t=3.85, P=0.001) and(1.14±0.25) mmol/L at 6 months( t=3.58, P=0.002). The average alkaline phosphatase(ALP) level decreased from(509.89±110.10) U/L before treatment to(447.89±106.76) U/L after 1 month( t=1.21, P=0.243). After 6 months, the ALP level significantly decreased to(385.89±60.33) U/L ( t=2.96, P=0.009). The average height percentile increased from 18.42±10.09 before treatment to 26.56±16.59 after 6 months( t=1.26, P=0.227). Rachitis severity scores of both lower limbs ranged from 4.61±1.36 before treatment to 3.06±1.51 after 6 months( t=2.29, P=0.036). No serious adverse events occurred during treatment. Conclusion:Burosumab is safe and effective in treating X-linked hypophosphatemic rickets, exhibiting minimal side effects and significant clinical applicability value.
5.Evaluation of the safety of radial artery puncture in neurointerventional surgery in elderly patients aged 75 years and older
Qiuju LI ; Ke PANG ; Hanlin CHEN ; Yue YIN ; Feng GAO ; Xuan SUN ; Ligang SONG ; Ning MA ; Dapeng MO ; Yiming DENG ; Zhongrong MIAO
Chinese Journal of Geriatrics 2024;43(10):1255-1259
Objective:To compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.
6.MicroRNA-148a-3p enhances sensitivity of radiotherapy of lung adenocarcinoma cells by targeting core 1β13-galactosyltransferase 1
Lin SHEN ; Yue REN ; Yizhou DENG ; Xudong YIN ; Yong CHEN
Journal of Clinical Medicine in Practice 2024;28(6):1-8
Objective To investigate the expression and clinical significance of microRNA-148a-3p (miR-148a-3p) in lung adenocarcinoma and analyze the effect and mechanism of miR-148a-3p on radiotherapy sensitivity of lung adenocarcinoma cells by targeting the protein core 1β13-galactosyltransferase 1(C1GALT1). Methods Seventy-six patients' tumor tissues from lung adenocarcinoma tissue microarrays and lung adenocarcinoma A549 cell line were selected for the study. The miR-148a-3p in situ hybridizations (ISH) and C1GALT1 immunohistochemical staining were performed on the tissue microarrays to analyze the correlations of miR-148a-3p expression with clinical pathology, prognosis and C1GALT1 expression in the tumor tissues of the 76 patients with lung adenocarcinoma. A549 cells were transfected with miR-148a-3p overexpression plasmid by using cell transfection technique; the clone formation assay was used to detect the sensitivity of the transfected cells for radiotherapy after receiving 2 Gy radiotherapy; the protein expression level of cellular C1GALT1 was detected by western blot; the targeted regulatory relationship between miR-148a-3p and C1GALT1 was verified by dual-luciferase reporter gene experiment; the mechanism of miR-148a-3p regulating the sensitivity of A549 cells to radiotherapy was analyzed by co-transfection technique. Results Low expression of miR-148a-3p in 76 cases of lung adenocarcinoma tissues was significantly associated with lymph node metastasis (
7.Machine and deep learning-based clinical characteristics and laboratory markers for the prediction of sarcopenia.
He ZHANG ; Mengting YIN ; Qianhui LIU ; Fei DING ; Lisha HOU ; Yiping DENG ; Tao CUI ; Yixian HAN ; Weiguang PANG ; Wenbin YE ; Jirong YUE ; Yong HE
Chinese Medical Journal 2023;136(8):967-973
BACKGROUND:
Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts.
METHODS:
We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models.
RESULTS:
The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749).
CONCLUSIONS:
The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population.
TRIAL REGISTRATION
Chictr.org, ChiCTR 1800018895.
Humans
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Aged
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Sarcopenia/diagnosis*
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Deep Learning
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Aging
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Algorithms
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Biomarkers
8.Interpretation of the clinical guideline for point-of-care ultrasonography in the neonatal intensive care unit in the United States.
Wen-Hui DONG ; Bo-Yin DENG ; Guang YUE ; Yasser ELSAYED ; Rong JU ; Jian-Hui WANG ; Yuan SHI
Chinese Journal of Contemporary Pediatrics 2023;25(7):672-677
In December 2022, the American Academy of Pediatrics released a clinical guideline for point-of-care ultrasonography (POCUS) in the neonatal intensive care unit (NICU). The guideline outlined the development and current status of POCUS in the NICU, and summarized the key elements and implementation guidelines for successful implementation of POCUS in the NICU. This article provides an overview of the key points of the clinical guideline and analyzes the current status of POCUS in China, providing a reference for the implementation of POCUS in neonatal care in China.
Infant, Newborn
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Humans
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United States
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Child
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Intensive Care Units, Neonatal
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Point-of-Care Systems
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Ultrasonography
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China
9.Investigation of the status of disaster preparedness and the influence path of psychological capital and perceived organizational support on it among pediatric nurses in Henan province
Shanshan WU ; Yuge PENG ; Meisu LU ; Wuying QIU ; Gaigai ZHENG ; Yue YIN ; Yufang DENG
Chinese Journal of Practical Nursing 2023;39(27):2120-2126
Objective:To investigate the status of disaster preparedness of pediatric nurses and its influencing factors, as well as the impact path of psychological capital and perceived organizational support on disaster preparedness.Methods:This was a cross-sectional study. A total of 361 pediatric nurses from Henan Provincial People ′s Hospital, the Third Affiliated Hospital of Zhengzhou University, Fuwai Central China Cardiovascular Hospital were sampled from August to October 2021. They were investigated by the general information questionnaire, psychological capital questionnaire, perceived organizational support questionnaire and disaster preparedness questionnaire. SPSS25.0 was used to analyze the questionnaire and scale data, and AMOS23.0 was used to construct a structural equation model about the disaster preparedness of pediatric nurses. Results:The scores of disaster preparedness from pediatric nurses was 4.65 ± 0.92. The level of disaster preparedness was significantly positively correlated with psychological capital and perceived organizational support ( r=0.690, 0.525, both P<0.05). Disaster training and emergency drill 2 dimensions of psychological capital questionnaire (hope, resilience), perceived organizational support were independent contributing factors ( P<0.05). Psychological capital had direct effect on disaster preparedness. And the direct effect was 0.77, the indirect effect was 0.11, the total effect was 0.88, and the direct effect of perceived organizational support on disaster preparedness was 0.21. Conclusions:The score of disaster preparedness of pediatric nurses was in the middle level. Hospital managers should strengthen the training of pediatric nurses in disaster knowledge, operational and simulation exercise, pay attention to the level of nurses' psychological capital and perceived organizational support, so as to provide reference for the follow-up clinical pediatric disaster nursing education and management.
10. METTL3-mediated m6A modification involved in electrical remodeling of atrial cardiomyocytes under high hydrostatic pressure
Pan-Yue LIU ; Fei-Fei XIAO ; Pan-Yue LIU ; Long ZENG ; Hai-Yin XIAO ; Fei-Fei XIAO ; Rui ZHU ; Hui YANG ; Su-Juan KUANG ; Chun-Yu DENG ; Fang RAO ; Wei WEI
Chinese Pharmacological Bulletin 2023;39(12):2258-2265
To investigate the regulation of N6- methyladenosine ( m6A ) modification on L-type calcium channels in atrial myocytes under high hydrostatic pressure, mediated by methyltransferase-like protein 3 ( METTL3 ). Methods C57BL/6J mice were randomly assigned to the control group and the hypertension group ( treated with continuous administration of angiotensin for four weeks ). Masson staining was used to observe the fibrosis of mouse atrial tissue, while dot blot assay and Western blot were used to detect the levels of m6A, METTL3, and Cavi1 2 in the atrial tissue. A high hydrostatic pressure model was constructed using the HL-1 cell line cultured in vitro, and METTL3 was intervened to observe changes in m6A expression levels, METTL3 and Cavi1 2 levels in cells,and action potential duration ( APD ) and L-type calcium current ( I


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