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.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.
4.Reducing language barriers, promoting information absorption, and communication using fanyi
Difei WANG ; Guannan CHEN ; Lin LI ; Shaodi WEN ; Zijing XIE ; Xiao LUO ; Li ZHAN ; Shuangbin XU ; Junrui LI ; Rui WANG ; Qianwen WANG ; Guangchuang YU
Chinese Medical Journal 2024;137(16):1950-1956
Interpreting genes of interest is essential for identifying molecular mechanisms, but acquiring such information typically involves tedious manual retrieval. To streamline this process, the fanyi package offers tools to retrieve gene information from sources like National Center for Biotechnology Information (NCBI), significantly enhancing accessibility. Additionally, understanding the latest research advancements and sharing achievements are crucial for junior researchers. However, language barriers often restrict knowledge absorption and career development. To address these challenges, we developed the fanyi package, which leverages artificial intelligence (AI)-driven online translation services to accurately translate among multiple languages. This dual functionality allows researchers to quickly capture and comprehend information, promotes a multilingual environment, and fosters innovation in academic community. Meanwhile, the translation functions are versatile and applicable beyond biomedicine research to other domains as well. The fanyi package is freely available at https://github.com/YuLab-SMU/fanyi.
5.Safety and efficacy of domestically produced novel bioabsorbable vascular scaff old in the treatment of complex coronary artery lesions for 3 years
Deng-Shuang ZHOU ; Qiong YOU ; Hai-Liang MO ; Zi-Jun WU ; Yu-Biao LIN ; Lu-Jun CHEN ; Jun-Yu FAN ; Yong-Jian LIN ; Rui-Sheng ZHANG ; Pei-Shan WAN ; Wei-Guo ZHOU ; Keng WU
Chinese Journal of Interventional Cardiology 2024;32(9):509-515
Objective To investigate the safety and efficacy of novel bioabsorbable vascular scaffold(BVS)in the treatment of patients with complex coronary artery disease.Methods This was a retrospective,matched,single-center observational study.45 patients with coronary atherosclerotic cardiopathy received BVS treatment in the cardiovascular medicine department Department of the Affiliated Hospital of Guangdong Medical University from June 2020 to June 2021(BVS),and 45 patients treated with drug-eluting stents(DES)group were selected according to matching study requirements during the same period.Baseline,surgical,and follow-up data were compared between the two groups to evaluate safety and efficacy.The main measures of safety were:surgical time,intraoperative adverse events,etc.,and the end point of efficacy was target lesion failure(TLF),including cardiac death,target vessel myocardial infarction,and ischa-driven target lesion revascularization.Results A total of 90 patients were enrolled in this study,all of whom were followed up for at least 3 years.There were 20 cases of bifurcation lesions and 25 cases of diffuse long lesions in the two groups,and 50 cases of imaging were reviewed among the 90 patients.The proportion of stable coronary heart disease,history of diabetes,history of hypertension,history of smoking,pre-dilated balloon pressure and postoperative diastolic blood pressure in BVS group was higher than that in DES group,and the proportion of family history was lower than that in DES group(all P<0.05).There were no statistically significant differences in the rates of cardiac death,target vessel myocardial infarction,and ischemia-driven revascularization of target lesions between the two groups(all P>0.05).Binary Logistic regression model analysis showed that the diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis(OR 2.786,95%CI 1.096-7.081,P=0.031).Conclusions Compared with traditional DES,BVS implantation has consistent safety and efficacy in the treatment of complex coronary artery disease within 3 years.The diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis.
6.Changing resistance profiles of Enterobacter isolates in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Shaozhen YAN ; Ziyong SUN ; Zhongju CHEN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yi XIE ; Mei KANG ; Fengbo ZHANG ; Ping JI ; Zhidong HU ; Jin LI ; Sufang GUO ; Han SHEN ; Wanqing ZHOU ; Yingchun XU ; Xiaojiang ZHANG ; Xuesong XU ; Chao YAN ; Chuanqing WANG ; Pan FU ; Wei JIA ; Gang LI ; Yuanhong XU ; Ying HUANG ; Dawen GUO ; Jinying ZHAO ; Wen'en LIU ; Yanming LI ; Hua YU ; Xiangning HUANG ; Bin SHAN ; Yan DU ; Shanmei WANG ; Yafei CHU ; Yuxing NI ; Jingyong SUN ; Yunsong YU ; Jie LIN ; Chao ZHUO ; Danhong SU ; Lianhua WEI ; Fengmei ZOU ; Yan JIN ; Chunhong SHAO ; Jihong LI ; Lixia ZHANG ; Juan MA ; Yunzhuo CHU ; Sufei TIAN ; Jinju DUAN ; Jianbang KANG ; Ruizhong WANG ; Hua FANG ; Fangfang HU ; Yunjian HU ; Xiaoman AI ; Fang DONG ; Zhiyong LÜ ; Hong ZHANG ; Chun WANG ; Yong ZHAO ; Ping GONG ; Lei ZHU ; Jinhua MENG ; Xiaobo MA ; Yanping ZHENG ; Jinsong WU ; Yuemei LU ; Ruyi GUO ; Yan ZHU ; Kaizhen WEN ; Yirong ZHANG ; Chunlei YUE ; Jiangshan LIU ; Wenhui HUANG ; Shunhong XUE ; Xuefei HU ; Hongqin GU ; Jiao FENG ; Shuping ZHOU ; Yan ZHOU ; Yunsheng CHEN ; Qing MENG ; Bixia YU ; Jilu SHEN ; Rui DOU ; Shifu WANG ; Wen HE ; Longfeng LIAO ; Lin JIANG
Chinese Journal of Infection and Chemotherapy 2024;24(3):309-317
Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5%in all clinical isolates amd 5.7%in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7%(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)%,followed by secretions/pus(16.4±2.3)%and urine(16.0±0.9)%.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9%),and only(7.1±0.8)%of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)%compared to the inpatients in any other departement.Overall,≤ 7.9%of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6%of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7%vs 3.9%).Overall,≤8.1%of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5%of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0%over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.
7.Prognostic Significance of Progression of Disease within 24 Months in Mantle Cell Lymphoma
Rui-Xue MA ; Qian-Qian ZHANG ; Hui-Min CHEN ; Jin HU ; Feng-Yi LU ; Qian-Nan HAN ; Zhen-Yu LI ; Kai-Lin XU ; Wei CHEN
Journal of Experimental Hematology 2024;32(3):702-707
Objective:To investigate the effect of progression of disease within 24 months(POD24)on overall survival(OS)in patients with mantle cell lymphoma(MCL),and compare the clinical characteristics between POD24 and non-POD24 patients.Methods:A retrospective analysis was performed on 50 MCL patients with treatment indications and regular treatment who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to August 2020.According to the occurrence of POD24,the patients were grouped for prognostic evaluation and clinical characteristics comparison.Results:Univariate Cox regression analysis showed that POD24,PLT,albumin,MIPI score,ECOG PS score,LDH were the factors influencing OS in newly diagnosed MCL patients(all P<0.05).The results of multivariate Cox regression analysis showed that POD24[HR=16.797(95%CI:3.671-76.861),P<0.001],albumin<40 g/L[HR=3.238(95%CI:1.095-9.572),P=0.034]and ECOG PS score≥2[HR=4.005(95%CI:1.033-15.521),P=0.045]were independent risk factors influencing OS in MCL patients.The incidence of PLT<100 × 109/L(33.3%vs 5.9%,P=0.033)and ECOG PS score≥2(45.5%vs 5.9%,P=0.040)were significantly higher in POD24 patients than those in non-POD24 patients.Conclusion:POD24 is an independent poor prognostic factor affecting the OS of MCL patients,and the patients with PLT<100 × 109/L and ECOG PS score ≥2 at diagnosis have a higher probability of POD24.
8.Effect of Endothelial Activation and Stress Index(EASIX)on Prognosis of Peripheral T-Cell Lymphoma Patients
Hui-Min CHEN ; Rui-Xue MA ; Qian-Qian ZHANG ; Feng-Yi LU ; Jin HU ; Qian-Nan HAN ; Zhen-Yu LI ; Kai-Lin XU ; Wei CHEN
Journal of Experimental Hematology 2024;32(5):1394-1400
Objective:To investigate the effect of endothelial activation and stress index(EASIX)on the prognosis of patients with angioimmunoblastic T-cell lymphoma(AITL)and peripheral T-cell lymphoma,not otherwise specified(PTCL-NOS),and to compare the clinical characteristics of patients in the low EASIX and high EASIX groups.Methods:The clinical data of 59 newly diagnosed AITL and PTCL-NOS patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to September 2021 were retrospectively analyzed.The optimal cut-off value of EASIX was determined by receiver operating characteristic(ROC)curve;The chi-square test was used to analyze the correlation between EASIX and clinical features of patients with AITL and PTCL-NOS;The Kaplan-Meier survival curve was used to analyze the overall survival(OS)and progression-free survival(PFS)of the patients;Univariate and multivariate analyses were performed by using Cox proportional hazards model.Results:The optimal cut-off value of EASIX was 0.95,based on which the patients were divided into a low EASIX(<0.95)group and a high EASIX(≥ 0.95)group.Compared with the low EASIX group,the high EASIX group had a higher proportion of patients with advanced Ann Arbor stage,higher risk according to IPI,elevated LDH,hypoproteinemia,anemia,B symptoms,extranodal involvement,and bone marrow involvement.Survival analysis showed that the OS and PFS of patients in the high EASIX group were significantly shorter than those in the lower EASIX group(P<0.001).The multivariate analysis showed that EASIX was an independent risk factor for OS[HR=7.217(95%CI:1.959-26.587),P=0.003]and PFS[HR=2.718(95%CI:1.032-7.161),P=0.043]of PTCL patients.Conclusion:High EASIX in newly diagnosed patients with AITL and PTCL-NOS suggests a poor prognosis,and high EASIX is a risk factor affecting prognosis of the patients.
9.Comparing Outcomes of Banana-Shaped and Straight Cages in Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Diseases: A Systematic Review and Meta-Analysis
Guang-Xun LIN ; Li-Ru HE ; Jin-Niang NAN ; Wen-Bin XU ; Keyi XIAO ; Zhiqiang QUE ; Shang-Wun JHANG ; Chien-Min CHEN ; Ming-Tao ZHU ; Gang RUI
Neurospine 2024;21(1):261-272
Objective:
This meta-analysis aims to refine the understanding of the optimal choice between different cage shapes in transforaminal lumbar interbody fusion (TLIF) by systematically comparing perioperative data, radiological outcomes, clinical results, and complications associated with banana-shaped and straight bullet cages.
Methods:
A meticulous literature search encompassing PubMed, Embase, Scopus, Web of Science, China Knowledge Network, and Wanfang Data was executed up to October 5, 2023. Inclusion criteria focused on studies comparing banana-shaped and straight bullet cages in TLIF. The quality of included studies was assessed using appropriate tools such as the Newcastle-Ottawa Scale (NOS) for nonrandomized studies. Rigorous evaluations were performed for radiographic outcomes, including disc height (DH), segmental lordosis (SL), lumbar lordosis (LL), subsidence, and fusion rates. Clinical outcomes were meticulously evaluated using visual analogue scale (VAS), Oswestry Disability Index (ODI), and complications.
Results:
The analysis incorporated 7 studies, involving 573 patients (297 with banana-shaped cages, 276 with straight cages), all with NOS ratings exceeding 5 stars. No statistically significant differences were observed in operative time, blood loss, or hospitalization between the 2 cage shapes. Banana-shaped cages exhibited greater changes in DH (p = 0.001), SL (p = 0.02), and LL (p = 0.01). Despite statistically higher changes in ODI for straight cages (26.33, p < 0.0001), the actual value remained similar to banana-shaped cages (26.15). Both cage types demonstrated similar efficacy in VAS, complication rates, subsidence, and fusion rates.
Conclusion
Although banana-shaped cages can excel in restoring DH, SL, and LL, straight bullet cages can provide comparable functional improvements, pain relief, and complication rates.
10.Efficacy and safety of tirzepatide for weight reduction in Chinese adults with overweight/obesity: A randomized clinical trial
Lin ZHAO ; Zhifeng CHENG ; Yibing LU ; Ming LIU ; Hong CHEN ; Min ZHANG ; Rui WANG ; Yuan YUAN ; Xiaoying LI
Chinese Journal of Endocrinology and Metabolism 2024;40(8):637-640
This article introduces a recent paper published in JAMA titled " Tirzepatide for weight reduction in Chinese adults with obesity: The SURMOUNT-CN randomised clinical trial". The paper details the design, results, and implications of a randomized controlled clinical study of the efficacy and safety of tirzepatide in overweight/obese adults in China(SURMOUNT-CN). This study represents the first Chinese evidence supporting tirzepatide for the treatment of obesity, offering a potent therapeutic option for the prevention and treatment of obesity and weight-related comorbidity.

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