1.Literature case analysis of drug-induced liver injury induced by GLP-1 receptor agonists
Menghua ZHANG ; Ying ZHU ; Ziyang WU ; Yanhua WANG ; Xiangzun XIONG ; Liyan MIAO
China Pharmacy 2025;36(20):2561-2565
OBJECTIVE To investigate the clinical characteristics of drug-induced liver injury (DILI) induced by glucagon- like peptide-1 receptor agonists (GLP-1RAs), and to provide a reference for safe clinical medication. METHODS Using search terms such as “GLP-1”“GLP-1RAs”“semaglutide” “drug-induced liver injury”, relevant studies from PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data and VIP were retrieved. Descriptive analysis was performed on cases of DILI induced by GLP-1RAs. RESULTS A total of 11 studies, comprising 11 patients, were included. Among them, 4 were male (36.4%) and 7 were female (63.6%). Patient ages ranged from 17 to 64 years; 5 patients (45.5%) were between 50 and 65 years old. Six patients were treated for diabetes, and five for weight loss. Ten patients had underlying diseases. The shortest time to the onset of DILI was 5 days after medication, while the longest was approximately 180 days. The DILIs induced by GLP-1RAs were mainly hepatocellular injury type (6 cases); severity levels included severe (3 cases), moderate (6 cases), and mild (2 cases). Gastrointestinal symptoms and jaundice were the most common clinical manifestations. The association between DILI and GLP- 1RAs was assessed as “probable” in 10 cases and “possible” in 1 case. All 11 patients improved after drug discontinuation and (or) corresponding treatment. CONCLUSIONS DILI induced by GLP-1RAs is relatively concentrated in patients aged 50-65, with a higher incidence in females. The risk may be further increased in patients with underlying diseases. Clinical use of these agents should enhance pharmaceutical care, including identification of high-risk populations and patient education (especially symptom recognition). When relevant symptoms appear, the drug should be discontinued immediately, with liver-protective therapy initiated when necessary, to ensure patient safety of drug use.
3.A practice guideline for therapeutic drug monitoring of mycophenolic acid for solid organ transplants.
Shuang LIU ; Hongsheng CHEN ; Zaiwei SONG ; Qi GUO ; Xianglin ZHANG ; Bingyi SHI ; Suodi ZHAI ; Lingli ZHANG ; Liyan MIAO ; Liyan CUI ; Xiao CHEN ; Yalin DONG ; Weihong GE ; Xiaofei HOU ; Ling JIANG ; Long LIU ; Lihong LIU ; Maobai LIU ; Tao LIN ; Xiaoyang LU ; Lulin MA ; Changxi WANG ; Jianyong WU ; Wei WANG ; Zhuo WANG ; Ting XU ; Wujun XUE ; Bikui ZHANG ; Guanren ZHAO ; Jun ZHANG ; Limei ZHAO ; Qingchun ZHAO ; Xiaojian ZHANG ; Yi ZHANG ; Yu ZHANG ; Rongsheng ZHAO
Journal of Zhejiang University. Science. B 2025;26(9):897-914
Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C0), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug-drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage*
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Drug Monitoring/methods*
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Humans
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Organ Transplantation
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Immunosuppressive Agents/administration & dosage*
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Delphi Technique
4.Interleukin-33 Knockout Promotes High Mobility Group Box 1 Release from Astrocytes by Acetylation Mediated by P300/CBP-Associated Factor in Experimental Autoimmune Encephalomyelitis.
Yifan XIAO ; Liyan HAO ; Xinyi CAO ; Yibo ZHANG ; Qingqing XU ; Luyao QIN ; Yixuan ZHANG ; Yangxingzi WU ; Hongyan ZHOU ; Mengjuan WU ; Mingshan PI ; Qi XIONG ; Youhua YANG ; Yuran GUI ; Wei LIU ; Fang ZHENG ; Xiji SHU ; Yiyuan XIA
Neuroscience Bulletin 2025;41(7):1181-1197
High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals
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Encephalomyelitis, Autoimmune, Experimental/metabolism*
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Astrocytes/metabolism*
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Interleukin-33/metabolism*
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HMGB1 Protein/metabolism*
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Acetylation
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Mice, Knockout
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Mice, Inbred C57BL
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p300-CBP Transcription Factors/metabolism*
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Mice
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Spinal Cord/metabolism*
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Cells, Cultured
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Female
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Signal Transduction
5.The effect of silica in soil on the extraction of biological evidence DNA at the crime scene using the silica bead method
Lu LU ; Zehua GAO ; Tianquan WU ; Liyan YU ; Shenbing GU ; Dongtao JIA
Chinese Journal of Forensic Medicine 2024;39(1):112-114
Objective To study the effect of silica in soil on the extraction of biological evidence DNA at the crime scene using the silica bead method.Methods Mud suspension and diluted blood were mixed to prepare biological samples mixed with dust and soil,which is to simulate biological evidence at the crime scene.Cell lysis was performed using heating lysis and guanidine salt chemical lysis,respectively.DNA was extracted using the silica bead method,amplified by PCR using Identifiler Plus kit and detected by capillary electrophoresis.The electrophoresis results were compared.Using mud suspension instead of silica beads to extract diluted blood DNA to validate the effect of silica in soil on the extraction of biological evidence DNA at crime scene using silica beads method.Results The complete STR loci were obtained after the extraction and amplification of 4 μL,20 μL dilute blood mixed with mud and lysed with heating cracking,whoes average peak heights arel 969.7±376.9 RFU and 9 706.7±349.8 RFU.For the 4 μL dilute blood mixed with mud guanidine salt chemical lysis,it cannot obtain complete STR loci after extraction and amplification.20 μL dilute blood mixed with mud guanidine salt was chemically cleaved and amplified to obtain complete STR loci with an average peak height of 1 899.8±801.3 RFU.After extraction and amplification by mud suspension instead of silica beads to extract 20 μL diluted blood DNA,complete STR loci were obtained.Conclusion Silicon dioxide in soil can bind to DNA in the presence of guanidine salts,leading to a decrease in the efficiency of recovering on-site biological evidence DNA using the silicon bead method.
6.Effect of rope-assisted proprioceptive neuromuscular facilitation combined with rope-assisted brain-computer in-terface training on upper limb function in stroke patients with hemiplegia:a randomized controlled trial
Tianjia LIANG ; Yaobin LONG ; Liyan LU ; Jinying ZHOU ; Fucai HUANG ; Linpeng HUANG ; Yingchao WU ; Yaoxiang LONG ; Xiaocui WEI ; Zhong LIU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(8):972-978
Objective To investigate the effect of combination of rope-assisted proprioceptive neuromuscular facilitation(PNF)training and rope-assisted brain-computer interface(BCI)training on upper limb function in stroke patients with hemiplegia. Methods From March,2022 to February,2023,96 inpatients with stroke hemiplegia from the Second Affiliated Hospital of Guangxi Medical University were randomly divided into conventional group(n=32),PNF group(n=32)and combined group(n=32).All the groups received routine rehabilitation treatment.The conventional group re-ceived upper limb PNF training,the PNF group received upper limb rope-assisted PNF training,and the com-bined group received both upper limb rope-assisted PNF training and upper limb rope-assisted BCI training,for four weeks.They were assessed with Functiongal Test for the Hemiplegic Upper Extremity-Hong Kong version(FTHUE-HK),Fugl-Meyer Assessment-Upper Extremities(FMA-UE)and modified Barthel Index(MBI)before and after treatment. Results The intra-group effect(F>341.219,P<0.001),inter-group effect(F>21.705,P<0.001)and interaction effect(F>3.171,P<0.05)were significant in the scores of FTHUE-HK and MBI.The intra-group effect(F=520.472,P<0.001)and inter-group effect(F=41.939,P<0.001)were significant in the scores of FMA-UE,and the interaction effect was not(P>0.05).After treatment,the FTHUE-HK,FMA-UE and MBI scores were the best in the combined group(P<0.05). Conclusion The combination of rope-assisted PNF training with rope-assisted BCI device training could further improve the motor function of the upper limbs in stroke patients with hemiplegia,and enhance their activities of daily liv-ing.
7.Analysis of the Difference of Plasma Soluble Glycoprotein A Expression in Positive and Negative Anti-M and Anti-"Mia"Levels in Healthy Blood Donors
Yanlian LIANG ; Linfeng WU ; Xiongchi TANG ; Yuqing SU ; Fan WU ; Shuang LIANG ; Liyan SUN
Journal of Modern Laboratory Medicine 2024;39(1):123-125
Objective To analyze the correlation between the expression of soluble glycoprotein A(GPA)in plasma of healthy blood donors and anti-M and anti-"Mia"antibodies.Methods Plasma from healthy donors from February 9,2022 to February 15,2023 was collected:irregular antibody-negative NN type(group Ⅰ,n=118)and MM type(group Ⅱ,n=51),anti-M antibody positive NN type(group Ⅲ,n=145)and anti-"Mia"antibody positive companion type(group Ⅳ,n= 87),the GPA content in plasma of different individuals in 4 groups was detected,and the difference in GPA expression was analyzed by t-test.Results The average plasma GPA contents in groupsⅠ,Ⅱ,Ⅲ and Ⅳ were 9.941±0.252,10.97±0.256,5.139±0.129 and 4.28±0.139ng/ml,respectively.The average GPA content of groups Ⅰ and Ⅱ was higher,and the average GPA content of groups Ⅲ and Ⅳ was lower,and the differences were statistically significant(all P<0.01).Conclusion The GPA content in plasma of healthy donors with anti-M and anti-"Mia"antibodies was significantly lower than that of the antibody-negative group.The results of this study lay a foundation for further investigation of whether GPA in plasma has the ability to neutralize anti-M and anti-"Mia"antibodies,improve disease diagnosis and safe blood transfusion.
8.Preliminary study on establishing diagnostic criteria for cold-dampness syndrome in rheumatoid arthritis based on Delphi method
Yunting XIAO ; Xiaodong WU ; Maojie WANG ; Kaixin GAO ; Liyan MEI ; Runyue HUANG ; Xiumin CHEN
International Journal of Traditional Chinese Medicine 2024;46(11):1393-1400
Based on the Delphi method, combined with the results of the previous literature study and expert interviews, 3 rounds of expert consultation were conducted to evaluate the degree of concentration of expert opinions and their importance from 3 aspects: arithmetic mean, full score ratio ( Ki), and rank sum ( Si), to construct a diagnostic scale for rheumatoid arthritis (RA) cold-dampness syndrome. In this study, 30 expert questionnaires were distributed in the 1st round, 30 questionnaires were recovered, and the expert coordination coefficient was 0.309; 30 expert questionnaires were distributed in the 2nd round, 30 questionnaires were recovered, and the expert coordination coefficient was 0.320; and 30 expert questionnaires were distributed in the 3rd round, 29 questionnaires were recovered, and the expert coordination coefficient was 0.387. The maximum value of the coefficient of variation of the experts of the 3 rounds was 0.27, and the minimum value was 0.09, suggesting that the consistency and credibility of the experts' evaluation of the importance of the entries of cold-dampness syndrome were high. In this study, the mean values and weights of 17 entries were finally obtained, of which the top 5 entries were cold pain in joints (4.793, 0.066 6); aggravated by cold (4.586, 0.063 7); white tongue coating (4.552, 0.063 2); aggravated in cloudy and rainy days (4.448, 0.061 8); and painful joints that are not warm to the touch (4.379, 0.060 8). This study completed the screening of relevant entries and conducted preliminary discussions, laying the foundation for constructing a diagnostic scale for RA cold-dampness syndrome and forming the final diagnostic criteria. The research method is scientific and reliable, which can provide reference for the diagnostic standard of RA cold-dampness syndrome, but further clinical practice research is still needed.
9.Development and Analysis of the Standard for Drug Use Monitoring and Evaluation
Jingjing ZHANG ; Liyan MIAO ; Jiancun ZHEN ; Jianguo ZHU ; Jun ZHANG ; Luwen SHI ; Ting XU ; Shiting LIU ; Bin WU
Herald of Medicine 2024;43(8):1212-1216
Drug use monitoring and evaluation play a key role in promoting drugs to return to clinical value,optimizing the basic medicine system,and improving the drug supply guarantee system.In order to promote the implementation of drug use monitoring and evaluation in medical institutions,the Pharmaceutical Affairs Committee of the Chinese Hospital Association led the efforts of organizing relevant domestic experts to follow the group standard development process.It successfully formulated the group standard of Drug Use Monitoring and Evaluation through the steps of problem sorting,framework construction,evidence collection,draft writing,opinion consultation,and standard formation.This article introduces the standard formulation process in detail,and explains and analyzes the content of the standard,aiming to help readers better understand the connotation of drug use monitoring and evaluation,and provide practical guidance.
10.Effects and Mechanisms of Chronic Intermittent Alcohol Exposure on Fear,Anxiety and Depression Behavior in Post-Traumatic Stress Mice
Liyan HAO ; Yibo ZHANG ; Yangxingzi WU
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2024;53(5):591-598
Objective This study aimed to explore the effects and mechanisms of chronic intermittent exposure to alcohol on fear,anxiety and depression behavior in post-traumatic stress disorder mice.Methods Thirty-six 8-week-old male C57BL/6J mice were randomly divided into a control group(Control),a traumatic stress disorder(PTSD)group and a chronic intermittent alcohol exposure(PTSD+Alcohol)group.The PTSD mice were prepared via the plantar electric shock method and then chroni-cally exposed to alcohol for 14 days.The fear,anxiety and depression behaviors of each group of mice were observed via a behav-ioral test.Western blotting was used to detect the expression levels of the microglial markers ionized calcium binding adapter molecule 1(IBA1),postsynaptic density protein 95(PSD95),and synaptotagmin Ⅰ(SYT1)in the hippocampal tissue of the mice in each group.Immunofluorescence staining was performed to assess the expression levels of IBA1 and Synaptophysin(SYN)in the hippocampal tissue.An enzyme-linked immunosorbent assay(ELISA)was used to measure the release of tumor necrosis fac-tor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the hippocampal tissue.Results Compared with those in the control group,the ratio of freezing time in the conditioned fear chamber significantly increased,the number of open arm entries decreased,the immobility time in the forced swim test increased in the PTSD group,and the expression of IBA1 protein and TNF-α release increased,with decreased expression of SYN,PSD95 and SYT1(all P<0.05).Compared with the PTSD group,the PTSD+Alcohol group presented significantly increased freezing time in the conditioned fear chamber,decreased locomotor distance and time spent in the center zone in the open field test,increased IBA1 protein expression,and increased release of TNF-α and IL-1β(all P<0.05).Conclusion Chronic intermittent alcohol exposure can aggravate fear,anxiety and depression in post-traumatic stress model mice,and the mechanism may be related to the activation of microglia.

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