1.The role of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in liver diseases
Yangling ZENG ; Yunyong WANG ; Haimei GUAN ; Tianwen WANG ; Baohua XIE ; Guobao LI ; Riyun ZHANG ; Tingshuai WANG ; Dewen MAO
Journal of Clinical Hepatology 2025;41(5):983-990
Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation, and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis, uptake, secretion, and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important, and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism, the degradation and regulatory mechanisms of HMGCR, and the application of inhibitors, as well as the role of HMGCR in liver diseases, in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.
2.Mechanism of action and potential value of the IRE1α/TRAF2/JNK pathway in the progression of acute liver failure
Haimei GUAN ; Kan ZHANG ; Weiyu CHEN ; Guobao LI ; Yangling ZENG ; Riyun ZHANG ; Tianwen WANG ; Baohua XIE ; Dewen MAO
Journal of Clinical Hepatology 2024;40(6):1281-1288
Acute liver failure(ALF)is one of the most critical liver diseases in clinical practice and seriously affects the life and health of Chinese people.Due to its high morbidity and mortality rates,unclear pathogenesis,and limited treatment methods,ALF has become a major problem that needs to be solved urgently in the field of liver diseases.In recent years,more and more studies have shown that endoplasmic reticulum stress is a key biological process in the progression of ALF,and the IRE1α/TRAF2/JNK pathway,as a part of endoplasmic reticulum stress signaling,plays a role in amplifying inflammatory response,promoting hepatocyte apoptosis,and inhibiting liver regeneration ability during the progression of diseases.As a traditional treasure of China,traditional Chinese medicine has become a research hotspot in search for effective prevention and treatment drugs for ALF from monomers of Chinese herbs.This article elaborates on the mechanism of action of the IRE1α/TRAF2/JNK pathway in the progression of ALF and summarizes the potential value of several monomers of Chinese herbs in regulating this pathway,such as salidroside,Fructus Broussonetiae,Fructus Psoraleae+Schisandra chinensis,baicalein,genipin,kaempferol,resveratrol,sea buckthorn polysaccharide extract,and luteol,in order to provide a reference for further research and clinical practice of ALF.
3.Exercise intervention for spinal curvature abnormality in children and adolescents:a bibliometrics analysis
Xuan LI ; Peng DOU ; Xuanchao WANG ; Haimei JIANG ; Jingyi RAO ; Shuping QIAN ; Chuhuai WANG ; Yi XU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(10):1140-1150
Objective To analyze the hotspots and frontiers of researches related to exercise intervention for spinal curvature abnor-malities in children and adolescents. Methods Articles related to exercise intervention for spinal curvature abnormalities in children and adolescents were re-trieved from CNKI and Web of Science Core Collection,from January,2014 to December,2023.The literatures were analyzed wtih CiteSapce 6.2.R3 in terms of disciplines,countries,institutes and keywords. Results A total of 233 articles were retrived,including 71 articles in Chinese and 162 articles in English.The annual pub-lication volume was on the rise.China was the country with the highest number of publications.South Korea was seen a sudden increase in recent literature.For Chinese,the institutions with the largest number of publication were the Department of Health and Exercise Science in Tianjin University of Sport and Luoyang Orthopedic-Traumatological Hospital of Henan Province(Henan Provincial Orthopedic Hospital).While the institutions with the largest number of publication in English were Marmara University and Hong Kong Polytechnic University.The English literatures covered a wide range of disciplines,including clinical medicine,sports medicine,neurolo-gy and psychology.Common high-frequency keywords in both Chinese and English literatures were idiopathic scoliosis,Cobb's angle and Schroth exercise.The latest bursting words included physical health in Chinese,and health-related quality of life and respiratory muscle strength in English. Conclusion The research popularity related to exercise intervention for spinal curvature abnormality in children and ado-lescents is generally on the rise.The research hotspots focus on four main areas:disease,quality of life,research advances and clinical treatment.More attention should be paid to the effect and dosage of exercise intervention on the respiratory function,as well as the effect of Chinese medicine exercise therapy on pediatric patients with abnormal spinal curvature diseases.Future work should focus on constructing an evidence-based Chinese/West-ern medicine exercise prevention and treatment system in the context of China's national conditions,advancing high-quality randomized controlled trials,strengthening interdisciplinary and international collaborations,and fo-cusing on the development and evaluation of personalized exercise intervention programs.
4.The Modulatory Effect of Yulian Pills on Memory Follicular Helper T Cells in Mice with Dextran Sulfate Sodium-Induced Ulcerative Colitis
Wen ZHOU ; Zheyan ZHANG ; Li HUANG ; Bailing DENG ; Duanyong LIU ; Wenxiao CHEN ; Haimei ZHAO
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(2):183-190
Objective To investigate the modulatory effect of Yulian Pills(composed of Coptidis Rhizoma and Euodiae Fructus)on splenic memory follicular T helper cell(mTfh)in mice with dextran sodium sulfate(DSS)-induced ulcerative colitis.Methods Forty BALB/c mice were randomly divided into normal group,model group,Yulian Pills group(0.5 g·kg-1)and Mesalazine group(0.3 g·kg-1),10 mice in each group.The mouse model of ulcerative colitis was induced by ad libitum drinking 3%DSS solution for 7 days.During the experiment,the mental state,faecal characteristics,blood in stool and body mass of the mice were recorded daily,and the length and mass of the colon were measured and the colon mass index was calculated;HE staining was used to observe the pathological and morphological changes of the colon tissue;ELISA was used to determine the expression levels of interleukin(IL)-6 and IL-15 in the colon tissues;flow cytometry was used to determine the mTfh cell subpopulation in the spleen tissue expression;Western Blot was used to determine the protein expression levels of Roquin-1,AMPK-α,p-AMPK-α in colon tissues.Results Compared with the normal group,the mice in the model group showed a significant decrease in body mass(P<0.01),a significant shortening of colon length(P<0.01),significant increase in colon mass(P<0.05)and colon mass index(P<0.01),and severe pathological damage to colon tissues;the expression levels of the pro-inflammatory cytokines IL-6 and IL-15 in the colon tissues were significantly increased(P<0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+ GL7+,CD4+CCR7-CXCR5+GL7+ were significantly increased in spleen tissues(P<0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly decreased(P<0.01);and protein expression levels of Roquin-1,AMPK-α,p-AMPK-α were significantly reduced in the colonic tissues(P<0.05).Compared with the model group,mice in the Yulian Pills group and Mesalazine group showed a significant increase in body mass(P<0.05),a significant extension of colon length(P<0.01),a significant reduction in colon mass(P<0.05),a significant decrease in the colon mass index(P<0.01),and a more obvious improvement in pathological damage of the colon tissues;a significant decrease in the expression levels of IL-6 and IL-15 in the colon tissues(P<0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+GL7+,CD4+CCR7-CXCR5+GL7+ in splenic tissues was significantly reduced(P<0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly increased(P<0.01);the protein expression levels of Roquin-1,AMPK-α,and p-AMPK-α were significantly increased in colon tissues(P<0.05,P<0.01).Conclusion The therapeutic effect of Yulian Pills on DSS-induced ulcerative colitis mice can ameliorate the histopathological damage of colon,which may be related to the activation of the Roquin-1/MPK-α signalling pathway,the down-regulation of the expressions of inflammatory cytokines IL-6 and IL-15,and the modulation of the homeostasis of the mTfh cell subpopulation.
5.Characteristics of brain cortical morphology in children with attention deficit hyperactivity disorder co-occurred with oppositional defiant disorder
Feifei SI ; Lu LIU ; Haimei LI ; Min DONG ; Qingjiu CAO ; Li SUN ; Qiujin QIAN ; Yufeng WANG
Chinese Mental Health Journal 2024;38(2):97-103
Objective:To investigate the characteristics of cortical morphology in children with attention defi-cit hyperactivity disorder(ADHD)and those with oppositional defiant disorder(ODD)from both categorical and dimensional analyses.Methods:A total of 72 children were enrolled,including 16 children with ADHD and ODD,20 children with ADHD without ODD,and 36 age-gender-matched normal children.The diagnoses were made ac-cording to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)criteria.The Chi-nese Wechsler Intelligence Scale for Children(C-WISC)was used to access intelligence quotient.All subjects par-ticipated in the magnetic resonance imaging(MRI)scan.The features of cortical morphology were determined using FreeSurfer software.Results:Children with ADHD and ODD[(6 528.1±857.5)mm3 vs.(7 591.2±657.3)]and children with ADHD only[(6 867.2±41.3)mm3 vs.(7 591.2±657.3)mm3]had smaller volume in the left later-al superior temporal gyrus(P<0.05)than controls.No difference was found between ADHD with ODD group and ADHD without ODD group.There was no correlation between the cortical volume of left lateral superior temporal gyrus and ODD symptoms.Conclusion:The reduced cortical volume of left lateral superior temporal gyrus may be an important indication of the abnormal brain structure of ADHD in children.And comorbid status of ODD dose not change this structural variation.
6.Correlation between parental emotional regulation difficulties and emotional regulation in children with attention deficit hyperactivity disorder
Xinxin YUE ; Ruonan LIU ; Qianrong LIU ; Haimei LI ; Yufeng WANG ; Lu LIU ; Qiujin QIAN
Chinese Mental Health Journal 2024;38(7):553-558
Objective:To explore the characteristics of parental emotional regulation(ER)and its influence on the ER of children with attention deficit hyperactivity disorder(ADHD).Methods:A total of 140 children with ADHD meeting the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)criteria and their parents,68 normal controls and their parents were recruited.ER was assessed using the Difficulties in Emotion Regulation Scale(DERS),Emotion Regulation Questionnaire(ERQ)and Emotion Regulation Checklist(ERC).Re-sults:Higher scores of DERS in emotion regulation strategies,impulse control and goal-directed behavior were found in parents of children with ADHD compared with parents of normal controls(Ps<0.05).The higher emo-tional lability(EL)of ERC and lower ER of ERC detected in children with ADHD were correlated with the emo-tion regulation strategies,impulse control and goal-directed behavior of their parents(Ps<0.01).The mediation an-alyses suggested that ER in children with ADHD may mediate the relationship of parental emotion regulation strate-gies and parental impulse control with children's EL.Conclusion:Parents of children with ADHD may exhibit emo-tional dysregulation in multiple subdimensions which might affect emotional regulation and aggravate the emotional lability of children with ADHD.
7.Characteristics of intertemporal choice in adults with attention deficit hyperactivity disorder
Haiheng HONG ; Caili CHEN ; Shiyu ZHANG ; Yi ZHOU ; Haimei LI ; Lu LIU ; Qiujin QIAN ; Yufeng WANG
Chinese Mental Health Journal 2024;38(12):1039-1044
Objective:To explore the characteristics of delay discounting and non-systematic response data in intertemporal choice of adults with attention deficit hyperactivity disorder(ADHD),and to explore the best data processing strategy for delay discounting task.Methods:Totally 108 adults with ADHD meeting the diagnostic cri-teria of the Diagnostic and Statistical Manual of Mental Health Disorder,Fifth Edition(DSM-5)and 87 gender matched normal controls were enrolled.ADHD symptoms were assessed using the ADHD Symptom Rating Scale,the delay discounting task was used to measure the delay discounting rate,and a model-free algorithm was used to i-dentify non-systematic response data.Results:There was no significant difference in the proportion of non-systemat-ic response data between ADHD group and normal control group(P>0.05).In the data sets using different data screening strategies,the delay discounting rates were higher in the ADHD group than in the normal control group(Ps<0.05).The delay discounting rates were positively correlated with the hyperactive impulse scores(r=0.24,P=0.001),the inattention scores(r=0.20,P<0.01)and the total scores of ADHD symptom Rating Scale(r=0.22,P<0.01).Conclusion:Adults with ADHD prefer to obtain immediate small rewards in intertemporal choice.The immediate preference of intertemporal choice may be mainly related to hyperactive impulsive symp-toms.Exclusion strategy of non-systematic response data may be more applicable to delay discount task research.
8.Cerebral Blood Flow Characteristics of Boys with Different Subtypes of Attention Deficit Hyperactivity Disorder and Their Relationship with Executive Function
Xinyi ZHANG ; Ningning LIU ; Haimei LI ; Yufeng WANG ; Lu LIU ; Qiujin QIAN
Medical Journal of Peking Union Medical College Hospital 2024;16(2):314-320
To analyze the differences in cerebral blood flow (CBF) characteristics among children with different subtypes of attention deficit and hyperactivity disorder (ADHD) and their relationship with executive function using arterial spin labeling (ASL) technology. A case-control study was conducted, including children diagnosed with ADHD at the outpatient clinic of Peking University Sixth Hospital from July 2015 to December 2019 as the ADHD group, and typically developing schoolchildren from January to December 2021 as the healthy control group. Both groups underwent pseudo-continuous ASL (pCASL) scanning to measure CBF, and executive function was assessed using the parent version of the Behavior Rating Inventory of Executive Function (BRIEF). Differences in CBF between ADHD children and healthy controls were compared. For brain regions showing significant group differences, CBF values were extracted and linear regression models were constructed with BRIEF scores to further explore the relationship between regional CBF and executive function. A total of 134 boys with ADHD were included[83 with ADHD predominantly inattentive subtype (ADHD-I) and 51 with ADHD combined subtype (ADHD-C)], along with 25 healthy control boys. Intergroup comparisons revealed that the CBF in the left middle temporal gyrus was significantly lower in ADHD-C children compared to both ADHD-I children ( The CBF in the left middle temporal gyrus of boys with ADHD-C is significantly lower than that of boys with ADHD-I and healthy controls. This reduced regional CBF may be associated with executive function deficits in organization and planning abilities in ADHD-C, providing new insights into the neurobiological mechanisms underlying ADHD subtypes.
9.Polymorphism of Estrogen Receptor Genes and Its Interactions With Neurodevelopmental Genes in Attention Deficit Hyperactivity Disorder Among Chinese Han Descent
Yiwei LIN ; Haimei LI ; Jing ZHANG ; Ziqi YANG ; Yi ZHOU ; Lu LIU ; Qiujin QIAN
Psychiatry Investigation 2023;20(8):775-785
Objective:
Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder with significant gender differences. The sexual dimorphism of ADHD may be associated with estrogen acting through estrogen receptors (ESR). This study investigates the impact of ESR gene polymorphism and its interactions with neurodevelopmental genes on ADHD susceptibility.
Methods:
The study compared genotyping data of single nucleotide polymorphisms in ESR1 and ESR2 in 1,035 ADHD cases and 962 controls. The gene-gene interactions between ESR genes and three neurodevelopmental genes (brain-derived neurotrophic factor [BDNF], synaptosomal-associated protein of 25 kDa gene [SNAP25], and cadherin-13 [CDH13]) in ADHD were investigated using generalized multifactor dimensionality reduction and verified by logistic regression analysis.
Results:
The G allele of rs960070/ESR2 (empirical p=0.0076) and the A allele of rs8017441/ESR2 (empirical p=0.0426) were found significantly higher in ADHD cases than in the controls but not in male or female subgroups. Though no difference was found in all subjects or females, the A allele of rs9340817/ESR1 (empirical p=0.0344) was found significantly higher in ADHD cases than controls in males. We also found genetic interaction models between ESR2 gene, neurodevelopmental genes and ADHD susceptibility in males (ESR2 rs960070/BDNF rs6265/BDNF rs2049046/SNAP25 rs362987/CDH13 rs6565113) and females (ESR2 rs960070/BDNF rs6265/BDNF rs2049046) separately, though it was negative in overall subjects.
Conclusion
The ESR gene polymorphism associates with ADHD among Chinese Han children, with interactions between ESR genes and neurodevelopmental genes potentially influencing the susceptibility of ADHD.
10.The Clinical Manifestation, Executive Dysfunction, and Caregiver Strain in Subthreshold Attention-Deficit/Hyperactivity Disorder
Yajing TANG ; Sunwei QIU ; Haimei LI ; Feifei SI ; Mengjie ZHAO ; Min DONG ; Meirong PAN ; Xinxin YUE ; Lu LIU ; Qiujin QIAN ; Yufeng WANG
Psychiatry Investigation 2023;20(9):789-798
Objective:
Subthreshold attention-deficit/hyperactivity disorder (ADHD) has been suggested to be a “morbid condition” which also needs medical attention.
Methods:
The present study recruited 89 children with subthreshold ADHD (sADHD), 115 children with diagnosed ADHD (cADHD), and 79 healthy controls (HC) to explore the clinical manifestation, executive functions (EFs) of sADHD, and the caregiver strain. The clinical manifestation was evaluated through clinical interviews and parent-reports. Executive functions were assessed both experimentally and ecologically. Caregiver strain was measured by a parent-reported questionnaire.
Results:
For the clinical manifestation, both sADHD and cADHD indicated impairments when compared with HC. The comorbidities and the scaled symptoms indicated that the externalizing behaviors were relatively less serious in sADHD than cADHD, whereas the internalizing behaviors between two groups were comparable. For ecological EFs, sADHD scored between cADHD and HC in inhibition and working memory. For experimental EFs, sADHD was comparable to cADHD in inhibition, shifting, and was worse than cADHD in verbal working memory. For the caregiver strain, all scores of sADHD were between that in cADHD and that in HC.
Conclusion
Our present findings supported the suggestion of subthreshold ADHD as “morbid condition,” which should be treated with caution in clinical practice, especially for the internalizing behaviors and some key components of EFs.

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