1.Influencing Factors of Urate Crystal Deposition in Patients with Hyperuricemia and Prediction Model of TCM Syndrome Types-inflammatory Indicators
Jiaqi XU ; Bin AI ; Chao LIN ; Qiaoxuan LIN ; Changning LI ; Jing CAI ; Yan XIAO ; Jiemei GUO ; Youxin SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):66-73
ObjectiveTo identify potential influencing factors of urate crystal deposition at ankle/foot in patients with hyperuricemia (HUA), and to analyze the predictive value of inflammatory indicators for urate crystal deposition in patients with different traditional Chinese medicine (TCM) syndromes, so as to provide potential reference for clinical risk assessment and individualized TCM intervention. MethodsA retrospective study was carried out with the enrollment of 231 HUA patients from The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2021 and December 2024. The enrolled patients were further divided into a crystal deposition-positive group (143 cases) and a crystal deposition-negative group (88 cases) according to the results of dual-energy computed tomography (CT). Sociodemographic data, living habits, serum uric acid levels, and inflammatory indicators of the enrolled patients were collcted, and TCM syndrome differentiation was performed. Furthermore, univariate analysis was used to compare inter-group differences in clinical characteristics. MMultivariate Logistic regression was applied to identify the influencing factors of urate crystal deposition. In addition, the receiver operating characteristic (ROC) curves were plotted to evaluate the predictive efficacy of inflammatory indicators for crystal deposition across different TCM syndromes. ResultsThere were statistically significant inter-group differences in the proportion of males, age, body mass index, proportion of mental labor, rate of low water intake, and rate of high-sugar beverage consumption (P<0.05),whereas no significant difference in low exercise intensity was found between the two groups. Furthermore, compared with the negative group, the positive group had higher serum uric acid level, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), but lower systemic immune-inflammation index (SIRI) (P<0.05). Regarding the distribution of TCM syndromes, the positive group was dominated by the dampness-heat accumulation syndrome (55/143,38.46%), while the negative group was mainly characterized by the phlegm-turbidity obstruction syndrome (44/88,50.00%). Multivariate Logistic regression analysis revealed that high-sugar beverage consumption, elevated NLR, and elevated PLR were risk factors for urate crystal deposition [odd ratio (OR) = 8.002, 5.377, 1.034, respectively; 95% CI 1.572-40.732, 2.179-13.270, 1.013-1.054,all P<0.05], while SIRI was a protective factor (OR = 0.869, 95% CI 0.778-0.971, P<0.05). In the positive group, patients with the dampness-heat accumulation syndrome exhibited the highest NLR, while the lowest PLR and SIRI, showing statistically significant differences with those of other syndromes (all P<0.05). In addition, ROC curve analysis indicated that for the dampness-heat accumulation syndrome, the combined "NLR + PLR" model had an area under the curve (AUC) of 0.901 (95% CI 0.850-0.951, P<0.01), with a sensitivity of 89.1% and a specificity of 79.5%; for the blood stasis-heat obstruction syndrome, the combined "NLR + PLR" model had an AUC of 0.880 (95% CI 0.825-0.934, P<0.01), with a sensitivity of 100.0% and a specificity of 67.3%; for the liver-kidney Yin-deficiency syndrome, the single PLR model had an AUC of 0.842 (95% CI 0.731-0.952, P<0.01), with a sensitivity of 83.3% and a specificity of 84.0%. ConclusionUrate crystal deposition in HUA patients exhibits intimate associations with high-sugar beverage consumption as well as elevated NLR and PLR levels. Meanwhile, TCM syndrome differentiation has potential correlation with inflammatory characteristics. The inflammatory indicator-based prediction model constructed based on TCM syndromes exhibits good predictive value.
2.Research on Development Path and Strategy of Human Use Experience in Traditional Chinese Medicine Based on Bibliometrics and Thematic Analysis
Yundan WU ; Qun CHEN ; Jie CHEN ; Yuhang OU ; Jindong WU ; Yan XIAO ; Jiemei GUO ; Jing CAI ; Youxin SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):118-128
ObjectiveThe development trend and knowledge structure of the research on human use experience (HUE) of traditional Chinese medicine (TCM) were systematically reviewed, and the core challenges and future directions were identified. This study aims to provide reference for the construction of a scientific and feasible research and development framework and evidence transformation system. MethodsLiterature related to "human use experience" published from January 1, 2019 to July 31, 2025 was retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang, China Science and Technology Journal Database (VIP), and PubMed databases. Bibliometric visualization was conducted using Excel, VOSviewer, and CiteSpace, followed by in-depth reading and thematic summarization of core literature. ResultsA total of 181 papers were included for bibliometric analysis, with 45 articles used for in-depth thematic mining. The analysis showed that the number of publications on HUE research has increased in a stepwise manner over the past five years. Yang Zhongqi (24 times) was the core of the author network, the journal with the highest number of publications was China Journal of Chinese Materia Medica, the institutions publishing the most articles were mainly research institutions, regulatory agencies, hospitals, and universities, high-frequency keywords included "new TCM drugs", "real-world studies", and "clinical comprehensive evaluation", keyword clustering analysis formed three major clusters: Policy orientation, application fields, and methodological approaches. Thematic analysis reveals that HUE-based evaluation should be integrated throughout the research and development process, encompassing three dimensions: TCM theory, clinical value, and pharmaceutical fundamentals, with toxic herbs and compatibility contraindications being key foci. Data collection primarily relies on empirical data, while real-world data constitute the primary source for clinical research, with efficacy and safety as the shared core. Data management emphasizes quality control and statistical analysis; however, the management of bias and confounding remains a critical bottleneck in evidence transformation. In practice, HUE-based approaches have successfully supported the registration and evaluation of multiple categories of new TCM drugs. ConclusionThe research on HUE of TCM has formed a policy-driven pattern characterized by, rapid development and close link with regulatory practice. A technical framework covering the whole chain of research and development has been constructed with clinical value as the core, which provides methodological basis and strategy reference for the scientific transformation of HUE of TCM from "experience" to "evidence".
3.Neuroelectromagnetic Activities Across Temporal Scales
Zhuo-Qun SHEN ; Xiao-Fei XU ; Yan-Qing WANG ; Jing-Xin LI ; Lan TIAN ; Wei GUO ; Jing-Jing XU
Progress in Biochemistry and Biophysics 2026;53(6):1541-1560
Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.
4.GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in metabolic dysfunction-associated steatohepatitis livers
Yi-Tong LI ; Wei-Qing SHAO ; Zhen-Mei CHEN ; Xiao-Chen MA ; Chen-He YI ; Bao-Rui TAO ; Bo ZHANG ; Yue MA ; Guo ZHANG ; Rui ZHANG ; Yan GENG ; Jing LIN ; Jin-Hong CHEN
Clinical and Molecular Hepatology 2025;31(2):409-425
Background/Aims:
Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation.
Methods:
The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation.
Results:
MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs.
Conclusions
In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.
5.GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in metabolic dysfunction-associated steatohepatitis livers
Yi-Tong LI ; Wei-Qing SHAO ; Zhen-Mei CHEN ; Xiao-Chen MA ; Chen-He YI ; Bao-Rui TAO ; Bo ZHANG ; Yue MA ; Guo ZHANG ; Rui ZHANG ; Yan GENG ; Jing LIN ; Jin-Hong CHEN
Clinical and Molecular Hepatology 2025;31(2):409-425
Background/Aims:
Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation.
Methods:
The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation.
Results:
MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs.
Conclusions
In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.
6.Risk factors of malaria infection and risk prediction model research in in labor export in Langfang City
Xuejun ZHANG ; Kun ZHAO ; Jing ZHAO ; ZHUO WANG ; Qiang GUO ; Jie XIAO ; Juanjuan GUO ; Jinhong PENG
Journal of Public Health and Preventive Medicine 2025;36(1):118-122
Objective To analyze the influencing factors of malaria infection of labor service exported to overseas in Langfang City, in order to establish a visualization tool to assist clinicians in predicting the risk of malaria. Methods A total of 4 774 expatriate employees of the Nibei Pipeline Project of the Pipeline Bureau from October 2021 to August 2023 were taken as the subjects, and the gender, age, overseas residence area and Knowledge of malaria controlscores of the study subjects were investigated by questionnaire survey, and the possible risk factors of malaria were screened by logistic regression model. At the same time, the nomogram prediction model was established, and the subjects were divided into the training group and the validation group at a ratio of 2:1, and the area under the curve (ROC) and the decision curve were plotted to evaluate the prediction ability and practicability of the prediction model in this study. Results Among the 4 774 study subjects, 96 cases of malaria occurred, and the detection rate was 2.01%. Junior school (OR=1.723,95% CI:1.361-2.173), and residence in rural areas(OR=2.091,95%CI:1.760 -3.100)were risk factors (OR>1), while protective measures(OR=0.826,95% CI : 0.781 - 0.901) and high malaria education scores (OR=0.872,95% CI : 0.621 - 0.899)were protective factors.The nomogram prediction model results showed that the area under the curve of the nomogram prediction model in the training group was 0.94 (95% CI : 0.85 - 1.00), while the validation group was 0.93 (95% CI : 0.80 - 1.00). The results of the decision curve showed that when the threshold probability of the population was 0-0.9, the nomogram model was used to predict the risk of malaria occurrence with the highest net income. Conclusion The nomogram prediction model (including gender, education, region, protection and malaria education score) established and validated in this study is of great value for clinicians to screen high-risk patients with malaria.
7.Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: A resting-state functional magnetic resonance imaging study.
Xuan YIN ; Xiao-Ling ZENG ; Jing-Jing LIN ; Wen-Qing XU ; Kai-Yu CUI ; Xiu-Tian GUO ; Wei LI ; Shi-Fen XU
Journal of Integrative Medicine 2025;23(2):159-168
OBJECTIVE:
Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA.
METHODS:
Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment.
RESULTS:
Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex.
CONCLUSION
EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals
;
Electroacupuncture
;
Male
;
Magnetic Resonance Imaging
;
Depression/diagnostic imaging*
;
Mice, Inbred C57BL
;
Brain/diagnostic imaging*
;
Disease Models, Animal
;
Mice
;
Pain/diagnostic imaging*
;
Acupuncture Points
8.Current situation of clinical trial registration in acupuncture anesthesia: A scoping review.
Yue LI ; You-Ning LIU ; Zhen GUO ; Mu-En GU ; Wen-Jia WANG ; Yi ZHU ; Xiao-Jun ZHUANG ; Li-Ming CHEN ; Jia ZHOU ; Jing LI
Journal of Integrative Medicine 2025;23(3):256-263
BACKGROUND:
Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias.
OBJECTIVE:
Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP).
SEARCH STRATEGY:
We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics.
INCLUSION CRITERIA:
Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review.
DATA EXTRACTION AND ANALYSIS:
Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment.
RESULTS:
A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41).
CONCLUSION
The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans
;
Acupuncture Analgesia
;
Acupuncture Therapy
;
Anesthesia
;
Clinical Trials as Topic
;
Registries
9.Associations of Exposure to Typical Environmental Organic Pollutants with Cardiopulmonary Health and the Mediating Role of Oxidative Stress: A Randomized Crossover Study.
Ning GAO ; Bin WANG ; Ran ZHAO ; Han ZHANG ; Xiao Qian JIA ; Tian Xiang WU ; Meng Yuan REN ; Lu ZHAO ; Jia Zhang SHI ; Jing HUANG ; Shao Wei WU ; Guo Feng SHEN ; Bo PAN ; Ming Liang FANG
Biomedical and Environmental Sciences 2025;38(11):1388-1403
OBJECTIVE:
The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress.
METHODS:
A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators.
RESULTS:
Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function.
CONCLUSION
Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans
;
Oxidative Stress/drug effects*
;
Male
;
Cross-Over Studies
;
Female
;
Young Adult
;
Environmental Pollutants/toxicity*
;
Environmental Exposure/adverse effects*
;
Biomarkers/blood*
;
Adult
;
Blood Pressure/drug effects*
;
Polycyclic Aromatic Hydrocarbons/urine*
;
Beijing
10.GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in metabolic dysfunction-associated steatohepatitis livers
Yi-Tong LI ; Wei-Qing SHAO ; Zhen-Mei CHEN ; Xiao-Chen MA ; Chen-He YI ; Bao-Rui TAO ; Bo ZHANG ; Yue MA ; Guo ZHANG ; Rui ZHANG ; Yan GENG ; Jing LIN ; Jin-Hong CHEN
Clinical and Molecular Hepatology 2025;31(2):409-425
Background/Aims:
Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation.
Methods:
The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation.
Results:
MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs.
Conclusions
In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.


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