1.Dissecting Causal Relationships Between Gut Microbiota, 1400 Blood Metabolites, and Intervertebral Disc Degeneration
Yuxi LIU ; Daxiong FENG ; Hong ZHANG ; Likun WANG
Neurospine 2025;22(1):211-221
Objective:
The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis.
Methods:
We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites.
Results:
Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041).
Conclusion
The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.
2.Dissecting Causal Relationships Between Gut Microbiota, 1400 Blood Metabolites, and Intervertebral Disc Degeneration
Yuxi LIU ; Daxiong FENG ; Hong ZHANG ; Likun WANG
Neurospine 2025;22(1):211-221
Objective:
The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis.
Methods:
We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites.
Results:
Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041).
Conclusion
The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.
3.Dissecting Causal Relationships Between Gut Microbiota, 1400 Blood Metabolites, and Intervertebral Disc Degeneration
Yuxi LIU ; Daxiong FENG ; Hong ZHANG ; Likun WANG
Neurospine 2025;22(1):211-221
Objective:
The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis.
Methods:
We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites.
Results:
Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041).
Conclusion
The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.
4.Dissecting Causal Relationships Between Gut Microbiota, 1400 Blood Metabolites, and Intervertebral Disc Degeneration
Yuxi LIU ; Daxiong FENG ; Hong ZHANG ; Likun WANG
Neurospine 2025;22(1):211-221
Objective:
The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis.
Methods:
We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites.
Results:
Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041).
Conclusion
The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.
5.Dissecting Causal Relationships Between Gut Microbiota, 1400 Blood Metabolites, and Intervertebral Disc Degeneration
Yuxi LIU ; Daxiong FENG ; Hong ZHANG ; Likun WANG
Neurospine 2025;22(1):211-221
Objective:
The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis.
Methods:
We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites.
Results:
Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041).
Conclusion
The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.
6.IMM-H007 promotes hepatic cholesterol and triglyceride metabolism by activating AMPKα to attenuate hypercholesterolemia.
Jiaqi LI ; Mingchao WANG ; Kai QU ; Yuyao SUN ; Zequn YIN ; Na DONG ; Xin SUN ; Yitong XU ; Liang CHEN ; Shuang ZHANG ; Xunde XIAN ; Suowen XU ; Likun MA ; Yajun DUAN ; Haibo ZHU
Acta Pharmaceutica Sinica B 2025;15(8):4047-4063
Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N 6-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe -/- and Ldlr -/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.
7.Value of diffusion tensor imaging in evaluating prognosis of cerebral hemorrhage related cerebral function
Lei HUANG ; Fei YE ; Likun WANG ; Guofeng WU
Chongqing Medicine 2024;53(12):1896-1900,1905
Intracerebral hemorrhage(ICH)is a nervous system disease that seriously endangers human health,with a very high rate of disability and fatality.Most survivors will leave behind varying degrees of neu-rological dysfunction.Therefore,early assessment of neurological function in the patients with cerebral hemor-rhage has an important clinical significance.Diffusion tensor imaging(DTI)is a nuclear magnetic resonance technique to noninvasively reconstruct the structure and path of nerve fiber bundles in vivo,which can be used to the condition evaluation and prognosis judgment after ICH,and has an important clinical significance for the evaluation of neurological dysfunction.This paper reviews the related value of DTI in the prognosis evaluation of the patients with ICH.
8.4 cases of occupational lung cancer caused by chloromethyl ether and dichloromethyl ether in a chemical enterprise
Likun SONG ; Jiechao WANG ; Qiuju TIAN ; Pan ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(10):772-775
Chloromethyl ether and diclomethyl ether are statutory substances that cause occupational lung cancer. From 2021 to 2022, the Department of Occupational Diseases of the Eighth People's Hospital of Hebei Province successively received 4 cases of lung cancer from a chemical company that required occupational disease diagnosis. All four patients had a clear occupational history of chloromethyl ether and diclomethyl ether for more than 1 year, diagnosis of primary small cell lung cancer supported by relevant histopathology, immunohistochemistry, and tumor markers. All the 4 patients were diagnosed as occupational lung cancer (chloromethyl ether, diclomethyl ether) .
9.4 cases of occupational lung cancer caused by chloromethyl ether and dichloromethyl ether in a chemical enterprise
Likun SONG ; Jiechao WANG ; Qiuju TIAN ; Pan ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(10):772-775
Chloromethyl ether and diclomethyl ether are statutory substances that cause occupational lung cancer. From 2021 to 2022, the Department of Occupational Diseases of the Eighth People's Hospital of Hebei Province successively received 4 cases of lung cancer from a chemical company that required occupational disease diagnosis. All four patients had a clear occupational history of chloromethyl ether and diclomethyl ether for more than 1 year, diagnosis of primary small cell lung cancer supported by relevant histopathology, immunohistochemistry, and tumor markers. All the 4 patients were diagnosed as occupational lung cancer (chloromethyl ether, diclomethyl ether) .
10.Correlation Between TyG Index,MHR and Coronary Lesions,Myocardial Ischemia in Patients with Coronary Heart Disease,and the Value of Combined Detection
Shuangshuang XU ; Wei ZHAO ; Lei JIANG ; Huajiang LIU ; Fang WANG ; Zhisheng TAN ; Likun ZHOU
Journal of Kunming Medical University 2024;45(3):65-71
Objective To investigate the correlation of triacylglycerol glucose(TyG)index,monocyte to high-density lipoprotein cholesterol ratio(MHR)with coronary artery disease and myocardial ischemia degree in coronary heart disease(CHD),and to analyze the two Predictive value of coronary artery disease and myocardial ischemia degree.Methods CHD patients from the 920th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force from January 2019 to January 2022 were selected as the study group(n = 150),and healthy physical examination subjects from the same period were selected as the control group(n = 75).The TyG index and MHR of the two groups were compared and analyzed.The extent of coronary artery disease was evaluated based on the Gensini score,and the TyG index and MHR of patients with different coronary lesions and myocardial ischemia were compared,and their correlation with Gensini score and myocardial ischemia was analyzed.The predictive value of TyG index,MHR,and the combined detection of both for coronary lesions and myocardial ischemia was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC).Results The TyG index and MHR of the study group were(4.12±0.35)and(0.26±0.08)×109,respectively,which were higher than those of the control group(4.94±0.55)and(0.43±0.12)×109,and the TyG index and MHR of severe coronary artery disease>moderate coronary artery disease>mild coronary artery disease,acute myocardial infarction TyG index,MHR>unstable angina pectoris>stable angina pectoris(P<0.05);TyG index and MHR were positively correlated with Gensini score(r = 0.621,0.635,P<0.05),and positively correlated with the severity of myocardial ischemia(r = 0.617,0.642,P<0.05).The AUC of TyG index and MHR for the joint identification of mild coronary artery disease and moderate coronary artery disease was 0.917,which was greater than the AUCs of 0.749 and 0.832 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of mild to moderate coronary artery disease and severe coronary artery disease was 0.935,which was greater than the AUCs of 0.770 and 0.767 for the two conditions individually(P<0.05).The AUC of TyG index and MHR for the joint identification of stable angina pectoris and unstable angina pectoris was 0.922,which was greater than the AUCs of 0.812 and 0.824 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of stable angina pectoris,unstable angina pectoris,and acute myocardial infarction was 0.913,which was greater than the AUCs of 0.708 and 0.714 for the two conditions individually(P<0.05).Conclusions TyG index and MHR are positively correlated with Gensini score and myocardial ischemia degree.The combined detection of the two has a higher application value in the evaluation of coronary artery disease and myocardial ischemia degree.

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