1.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.
2.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.
3.Predictive value of triglyceride, glycosylated hemoglobin and their interactions on gestational diabetes mellitus
Zichao BAO ; Cheng TAO ; Dianchen CHEN
Shanghai Journal of Preventive Medicine 2025;37(4):361-367
ObjectiveTo investigate the diagnostic value of triglyceride (TG) and glycosylated hemoglobin (HbA1c) and their interactions on gestational diabetes mellitus (GDM), so as to provide a basis for future pregnancy monitoring and clinical decision-making. MethodsData of 100 full-term singleton pregnant women who were examined and delivered in the Second People’s Hospital of Wuhu City from January 2020 to January 2023 were retrospectively collected, and they were divided into GDM group (n=33) and non-GDM group (n=67) according to the results of oral glucose tolerance test (OGTT). The general clinical data of the two groups were compared, and the independent risk factors affecting the occurrence of GDM were analyzed using logistic regression analysis. Furthermore, the diagnostic value of the interaction of HbA1c and TG on GDM was analyzed using additive interaction model. A nomogram model to predict the occurrence of GDM was constructed and verified. The effects of HbA1c, TG and their interactions on the occurrence of GDM were analyzed using the receiver operating characteristic curve (ROC). ResultsHbA1c and TG were significantly higher in the GDM group than those in the non-GDM group (P<0.001). History of GDM, family history of diabetes mellitus, body mass index (BMI) before pregnancy, hypertension, TG, frequent consumption of high-calorie food during pregnancy, and HbA1c were the influencing factors for the occurrence of GDM in pregnant women (P<0.001). The nomogram model was constructed according to the seven factors screened by logistic regression analysis, and the average absolute error between the predicted probability by the nomogram model and actual probability of the occurrence of GDM was 0.039. The ROC results showed that the area under the curve (AUC) value of HbA1c was 0.765, the AUC value of TG was 0.833, and the AUC value of the interaction between TG and HbA1c was 0.894, with a statistically significant difference (P<0.05). ConclusionHbA1c and TG are not only influencing factors for GDM, but also their interactions are positively correlated with the occurrence of GDM. The diagnostic value of the two synergistically interacting on GDM is greater than that of them independently on GDM. The nomogram model constructed in this study has good differentiation, accuracy and clinical practicability for predicting the incidence of GDM.
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.Analysis of Alleviating Effect of Calcium Cyanamide on Replanting Problems of Rehmannia glutinosa
Lianghua LIN ; Hengrui ZHANG ; Haoxiang YU ; Fan YANG ; Yufei WANG ; Caixia XIE ; Tao GUO ; Zhongyi ZHANG ; Liuji ZHANG ; Bao ZHANG ; Suiqing CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):212-222
ObjectiveTo investigate the alleviating effect of calcium cyanamide (CaCN2) soil fumigation on replanting problems of Rehmannia glutinosa. MethodsNewly soil (NP) was used as the control group, while three treatment groups were established: replanted soil (RP), newly soil treated with CaCN2 (120 g·m², tillage depth 25 cm) (NPCC), and replanted soil treated with CaCN2 (RPCC). R. glutinosa was cultivated in all groups. At harvest, the tuber agronomic traits (number of enlarged roots, maximum root diameter, fresh weight, dry weight) were measured. The content of catalpol and rehmannioside D was quantified by ultra-high-performance liquid chromatography (UPLC) to evaluate medicinal quality. Rhizosphere soil available nutrients and enzyme activities were analyzed by assay kits. The community structure and composition of fungi and bacteria in rhizosphere soil were assessed via internal transcribed spacer 2 (ITS2) sequencing and 16S rDNA sequencing, respectively. ResultsCompared with NP, the RP group showed obviously reduced in tuber agronomic traits and quality indicators (P0.05). However, the RPCC group showed significant improvement in agronomic traits and a notable increase in rehmannioside D content compared to RP (P0.05). The contents of available phosphorus and potassium in RPCC and NP groups were obviously lower than those in RP (P0.05). The polyphenol oxidase soil (S-PPO) activity in RP was obviously lower than in NP (P0.05), while sucrose soil (S-SC), acid phosphatase soil (S-ACP), and S-PPO activities in RPCC were obviously higher than in RP (P0.05). Microbial richness and diversity in RP were obviously higher than in NP (P0.05), whereas no significant differences were observed between the RPCC and NP. The relative abundances of fungal genera Nectria, Myrothecium, Tomentella, and bacterial genus Skermanella were obviousl lower in RPCC and NP than in RP (P0.05). Correlation analysis that S-ACP activity was positively correlated with the content of rehmannioside D (P0.05). Fungal genera Engyodontium and Alternaria, and bacterial genera Pir4 lineage, Pirellula, Methyloversatilis, Brevundimonas, Ralstonia, and Acidibacter were obviously positively correlated with tuber dry weight (P0.05). Conversely, fungal genera Pseudaleuria, Nectria, Haematonectria, Ceratobasidium, and bacterial genera Streptomyces, Skermanella, RB41, Gemmatimonas, and Bacillus were obviously negatively correlated with dry weight (P0.05). The fungal genus Alternaria and bacterial genera Brevundimonas, Ralstonia, Acidibacter, and Dongia showed positive correlations with medicinal quality of R.glutinosa tuber, while fungal genera Pseudaleuria, Nectria, Stachybotrys, Fusarium, Gibberella, Ceratobasidium, and bacterial genera Sphingomonas, Skermanella, RB41, Gemmatimonas, and Bacillus were obviously negatively correlated (P0.05). ConclusionCaCN2 soil fumigation can significantly improve enzyme activities in replanted Rehmannia rhizosphere soil, enhance the utilization of available nutrients, reshape microbial community structure of replanted R.glutinosa at the family and genus level, and notably improve tuber agronomic traits and medicinal quality. This study provides a novel approach to alleviating replanting problems and offers insights for the integrated development of standardized cultivation techniques, including soil disinfection, nutrient-targeted regulation, and microbial inoculant application.
6.Construction and evaluation of novel self-assembled nanoparticles of Herpetospermum caudigerum Wall.
Yu-wen ZHU ; Xiang DENG ; Li CHEN ; Jian-tao NING ; Yu-ye XUE ; Bao-de SHEN ; Ling-yu HANG ; Hai-long YUAN
Acta Pharmaceutica Sinica 2024;59(2):448-454
It has become an industry consensus that self-assembled nanoparticles (SAN) are formed by molecular recognition of chemical components in traditional Chinese medicine during the decoction process. The insoluble components in the decoction are mostly in the form of nanoparticles, which can improve the problem of poor water solubility. However, the transfer rate of these insoluble components in the decoction is still very low, which limits the efficacy of the drug. This study aimed to refine the traditional decoction self-assembly phenomenon. The self-assembled nanoparticles were constructed by micro-precipitation method (MP-SAN), and characterized by particle size, zeta potential, stability index and morphology. The formation of MP-SAN and alterations in related physicochemical properties were evaluated using modern spectroscopic and thermal analysis techniques. The quality value transmitting pattern of lignan components within the MP-SAN was assessed
7.Investigation of Pharmacodynamic Components of Allii Macrostemonis Bulbus in Treatment of Hyperlipidemia by Ultra-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry and Targeted Network Pharmacology Combined with Molecular Docking
Yi-Kai WANG ; Jin-Xu DONG ; Yu-Tao BAI ; Rui WANG ; Xin HUANG ; Chang-Bao CHEN ; Hao YUE ; Tong LIU ; De-Hui YANG
Chinese Journal of Analytical Chemistry 2024;52(4):578-586
The main chemical components of Allii Macrostemonis Bulbus and components in serum were analyzed and identified rapidly and precisely by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)technique in this study.The compounds were identified based on the relative molecular mass,fragmentation ions,and retention time of chromatographic peaks.A total of 36 kinds of chemical components were identified from Allii Macrostemonis Bulbus,including 28 kinds of saponins,3 kinds of amino acids,2 kinds of flavonoids,one kind of organosulfur compound,one kind of nucleoside,and one kind of hormone-lipid compound.In addition,8 kinds of compounds of Allii Macrostemonis Bulbus were identified from the serum.Based on the intersection compounds of which detected in serum and screened out by TCMSP platform database,by using targeted network pharmacology and molecular docking technology,a"drug-component-target-pathway"association network was constructed.Naringenin,quercetin,macrostemonoside E and 25(R)-26-O-β-D-glucopyranosyl-22-hydroxy-5β-furostan-3-O-β-D-glucopyranosyl(1→2)-β-D-glucopyranoside were screened as the main active constituents of Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.In addition,adenosine 5′-monophosphate-activated protein kinase(AMPK),tumor necrosis factor(TNF),vascular endothelial growth factor A(VEGFA)and matrix metallopeptidase 9(MMP9)were the key action targets for Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.Molecular docking was performed using the main pharmacodynamic components and key action targets.The results indicated that all the four active components showed strongly bound to AMPK.This suggested that the regulation of lipid metabolism might be the key mechanism of Allii Macrostemonis Bulbus in antihyperlipidemic effect.This study provided a data reference for the research on the pharmacodynamic components of Allii Macrostemonis Bulbus,and provided a basis for the improvement of quality standard of Allii Macrostemonis Bulbus.
8.Three-dimensional finite element analysis of lumbar disc herniation under different body positions
Ben-Jing YIN ; Yu LU ; Fu-Tao JI ; Rong-Neng QIU ; Yuan-Yang XIE ; Ge CHEN ; Tian-Li XU ; Chao-Yu BAO ; Ju-Bao LI
China Journal of Orthopaedics and Traumatology 2024;37(6):599-604
Objective To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation(LDH)by finite element analysis.Methods Lumbar CT image of a 48-year-old female patient with LDH(heighted 163 cm,weighted 53 kg)was collected.Mimics 20.0,Geomagic Studio,Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments.Compression techniques under horizon-tal position,30° forward bending and 10° backward extension were simulated respectively.After applying the pressure,the ef-fects of compression techniques under different positions on stress,strain and displacement of various tissues of intervertebral disc and nerve root were observed.Results L4,5 segment finite element model was successfully established,and the model was validated.When compression manipulation was performed on the horizontal position,30° flexion and 10° extension,the annular stress were 0.732,5.929,1.286 MPa,the nucleus pulposus stress were 0.190,1.527,0.295 MPa,and the annular strain were 0.097,0.922 and 0.424,the strain sizes of nucleus pulposus were 0.153,1.222 and 0.282,respectively.The overall displace-ment distance of intervertebral disc on Y direction were-3.707,-18.990,-4.171 mm,and displacement distance of nerve root on Y direction were+7.836,+5.341,+3.859 mm,respectively.The relative displacement distances of nerve root and interverte-bral disc on Y direction were 11.543,24.331 and 8.030 mm,respectively.Conclusion Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend,by increasing the distance between herniated interverte-bral disc and nerve root,to reduce symptoms of nerve compression,to achieve purpose of treatment for patients with LDH,in which the compression manipulation is more effective when the forward flexion is 30°.
9.Effect of polydimethylsiloxane membrane on the quality characteristics of medium borosilicate glass tube injection bottles
Jianzhang LIU ; Tao ZHANG ; Jian BAO ; Yuchi HU ; Zhishun CHEN ; Xu LIU ; Nan JIANG
Drug Standards of China 2024;25(3):307-312
Objective:To investigate effects of polydimethylsiloxane coating on the quality characteristics and qual-ity control methods of medium borosilicate glass tube injection bottles,including appearance,identification,physi-cal properties,water resistance of inner surface and element leaching amount.Methods:Nine batches of coated medium borosilicate glass tube injection bottles and corresponding medium borosilicate glass tube injection bottles from three companies were used to evaluate whether the quality control method of medium borosilicate glass tube in-jection bottles after polydimethylsiloxane film was modified,and to evaluate the effect of coating on the quality char-acteristics of bottles.Results:The coating did not have effect on appearance,identification and physical properties of medium borosilicate glass tube injection bottle.The coating process did not damage the original performance of the medium borosilicate glass tube injection bottle,and lead to the matters with special attention on the inspection method.The water resistance of the inner surface of the coated medium borosilicate glass tube injection bottle was improved.The leaching amounts of harmful elements such as arsenic,antimony,lead and cadmium before and after coating were low,indicating that the coating process did not increase the leaching risk of these harmful elements.The leaching amounts of elements were determined by ICP-OES,and no significant changes were found in most metal elements.Conclusion:The appearance,identification,physical properties and element leaching quality con-trol method of medium borosilicate glass tube injection bottle after poly dimethylsiloxane film coating do not need to be changed.The water resistance of the inner surface after coating is improved,and there is no significant adverse effect on other quality characteristics.
10.Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome (version 2024)
Junyu WANG ; Hai JIN ; Danfeng ZHANG ; Rutong YU ; Mingkun YU ; Yijie MA ; Yue MA ; Ning WANG ; Chunhong WANG ; Chunhui WANG ; Qing WANG ; Xinyu WANG ; Xinjun WANG ; Hengli TIAN ; Xinhua TIAN ; Yijun BAO ; Hua FENG ; Wa DA ; Liquan LYU ; Haijun REN ; Jinfang LIU ; Guodong LIU ; Chunhui LIU ; Junwen GUAN ; Rongcai JIANG ; Yiming LI ; Lihong LI ; Zhenxing LI ; Jinglian LI ; Jun YANG ; Chaohua YANG ; Xiao BU ; Xuehai WU ; Li BIE ; Binghui QIU ; Yongming ZHANG ; Qingjiu ZHANG ; Bo ZHANG ; Xiangtong ZHANG ; Rongbin CHEN ; Chao LIN ; Hu JIN ; Weiming ZHENG ; Mingliang ZHAO ; Liang ZHAO ; Rong HU ; Jixin DUAN ; Jiemin YAO ; Hechun XIA ; Ye GU ; Tao QIAN ; Suokai QIAN ; Tao XU ; Guoyi GAO ; Xiaoping TANG ; Qibing HUANG ; Rong FU ; Jun KANG ; Guobiao LIANG ; Kaiwei HAN ; Zhenmin HAN ; Shuo HAN ; Jun PU ; Lijun HENG ; Junji WEI ; Lijun HOU
Chinese Journal of Trauma 2024;40(5):385-396
Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

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