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.Epidemiological characteristics of pertussis in Harbin City from 2015 to 2024
ZHANG Junjie ; LUO Chao ; JIANG Likun ; ZHANG Huiying
Journal of Preventive Medicine 2025;37(9):941-944
Objective:
To investigate the epidemiological characteristics of pertussis in Harbin City from 2015 to 2024, so as to provide the basis for formulating pertussis prevention and control measures.
Methods:
The incidence data of pertussis in Harbin City from 2015 to 2024 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System, and the vaccination data were collected through the Immunization Program Information System of Heilongjiang Province. Descriptive epidemiological methods were used to analyze the temporal, regional and population distribution characteristics of pertussis incidence as well as the immunization history of pertussis cases.
Results:
A total of 417 cases of pertussis were reported in Harbin City from 2015 to 2024, with an average annual reported incidence of 0.41/100 000. The reported incidence increased from 0.18/100 000 in 2015 to 0.64/100 000 in 2024, showing an overall upward trend (P<0.05). The peak incidence period was from August to November, with 253 cases, accounting for 60.67%. The average annual reported incidences of pertussis in Shuangcheng District, Nangang District and Daoli District were relatively high, at 1.09/100 000, 0.93/100 000 and 0.52/100 000, respectively. There were 223 male cases and 194 female cases, with a male-to-female ratio of 1.15∶1. The average annual reported incidence of pertussis was 0.45/100 000 in males and 0.39/100 000 in females, with no statistically significant difference (P>0.05). Cases were predominantly distributed among children under 6 months and those aged 6 to under 10 years, with 176 and 144 cases, accounting for 42.21% and 34.53% respectively. The majority of cases were scattered children, with 266 cases (63.79%). There were 175 cases (41.97%) without diphtheria-tetanus-pertussis (DTP) vaccine and 172 cases (41.25%) who had completed the full course of immunization.
Conclusions
The incidence of pertussis in Harbin City showed an upward trend from 2015 to 2024. Autumn was identified as the peak season for disease onset. Shuangcheng District and Nangang District were the high-incidence areas. Children under 6 months, those aged 6 to under 10 years, scattered children, and those who had not received the DTP vaccine were the high-risk groups. It is recommended to improve pertussis surveillance strategies and strengthen childhood immunization programs.
7.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.
8.Prediction of early treatment outcomes in patients with traumatic brain injury using transcranial Doppler ultrasound combined with invasive intracranial pressure
Meng'ai ZHAI ; Li ZHANG ; Yang YANG ; Yuhai WANG ; Likun YANG ; Yang YANG
Journal of Army Medical University 2025;47(22):2783-2791
Objective To investigate the predictive role of transcranial Doppler(TCD)ultrasound combined with invasive intracranial pressure(ICP)monitoring in the early outcomes for patients with moderate-to-severe traumatic brain injury(msTBI)after ICP probe insertion surgery.Methods A retrospective case-control analysis was conducted on the clinical data of 65 msTBI patients who underwent invasive ICP probe insertion surgery within 24 h after injury and routine TCD examination postoperatively in No.904 Hospital of Joint Logistic Support Force of Chinese PLA between January 2021 and March 2025.Based on whether disease progression met the indications for craniotomy,they were divided into a failed conservative treatm ent group(n=28)and a successful conservative treatment group(n=37).Baseline clinical data,and parameters of TCD and ICP monitoring were collected in both groups.Univariate analysis was used for comparing differences in various parameters between the groups.The variables related to ICP and TCD were denoted as Model 1,and variables that significantly affected the outcome were incorporated as potential confounding factors into Model 2 based on clinical experience.Multivariate logistic regression analysis was performed to screen for independent predictors of conservative treatment failure.Receiver operating characteristic(ROC)curves were plotted to evaluate the diagnostic efficacy of each predictive factor.Results Statistical differences were observed between the 2 groups in terms of Glasgow Coma Scale(GCS)score at admission,postoperative mean intracranial pressure(ICPm),postoperative mean cerebral perfusion pressure(CPPm),and pulsatility index(PI)of the ipsilateral internal carotid artery extracranial segment(ICAt),and mean flow velocity(Vm)and pulsatility index(PI)of the ipsilateral middle cerebral artery(MCA)(all P<0.01).After adjusting for age,GCS score at admission,hematoma volum,and mean postoperative brain temperature,multivariate logistic regression analysis revealed that ICPm(OR=1.248,95%CI:1.044~1.491,P=0.015),ipsilateral MCA.Vm(OR=0.964,95%CI:0.933~0.997,P=0.034),and ipsilateral MCA.PI(OR=1.612,95%CI:1.026~2.533,P=0.038)were independent predictors of failure in conservative treatment in msTBI patients.After adjustment,ROC curve analysis demonstrated that the combined model of ipsilateral MCA.PI,ipsilateral MCA.Vm,and ICPm achieved a predictive efficacy of 0.931(95%CI:0.873~0.988),which was obviously higher than that of the single model of ICPm(0.875,95%CI:0.791~0.959).Conclusion Combined monitoring of TCD and ICP can provide a more accurate prediction of the early outcomes for msTBI patients after ICP probe insertion,providing a more effective assessment for clinical diagnosis and treatment.
9.Research and verification of oxygen consumption forecast model for extravehicular activity
Changsheng TIAN ; Wanxin ZHANG ; Zongbao FU ; Likun YAO ; Qianfang LIAO ; Shiyao LUO ; Qi TIAN
Space Medicine & Medical Engineering 2025;36(2):178-182
Aiming at the problem that the amount of Oxygen remaining and available time can not be accurately predicted while an astronaut conducting extravehicular activities(EVAs)in EVA spacesuit.Research the oxygen consumption process of EVA spacesuit.The model and algorithm of oxygen consumption are established by the gas state equation including compressibility and temperature coefficient,combined with human metabolism and micro leakage characteristics of spacesuit.Experimental data show that the orecast model and algorithm hasing high accuracy and practicability.
10.Rational analysis of the use of antiemetic drugs in tumor chemotherapy patients in our hospital
Danjun REN ; Juanli ZHANG ; Meiyou LIU ; Likun DING ; Tingting FAN ; Di ZHANG ; Jingwen WANG ; Aidong WEN
China Pharmacy 2024;35(12):1495-1499
OBJECTIVE To provide reference for the rational use of antiemetic drugs in tumor chemotherapy patients. METHODS The data of tumor patients who were given antiemetic drugs were collected from 9 departments of our hospital with hospital information system from Oct. 1st to Nov. 30th in 2022, such as oncology department, radiotherapy department, gynecology department, and gastroenterology department. The application of chemotherapy drugs and the use of antiemetic drugs were analyzed statistically, and the irrational use of antiemetic drugs was analyzed. RESULTS A total of 520 patients were included, involving 248 (47.69%) using chemotherapy drugs with a moderate emetogenic risk level and 135 (25.96%) with a high emetogenic risk level. A total of 461 cases (73.06%) of 5-hydroxytryptamine 3-receptor antagonists were used, including palonosetron in 333 cases, ondansetron in 106 cases, tropisetron in 15 cases and granisetron in 7 cases, and only 148 cases of patients were prioritized for the use of nationally procured medicines and national essential medicines (32.10%). Neurokinin-1 receptor antagonists were used in 170 cases (26.94%), including fosaprepitant in 112 cases and aprepitant in 58 cases. The use of antiemetic drugs was unreasonable in 162 patients (31.15%); among the types of irrational drugs, the antiemetic regimen was unreasonable in the largest number of cases (22.40%), followed by the irrational pharmacoeconomics (19.13%). CONCLUSIONS The emetogenic risk levels of chemotherapy drugs used for tumor patients in our hospital are primarily moderate to high, and there is irrational use of antiemetic regimen and pharmacoeconomics. Clinicians, nurses, pharmacists and hospital departments should collaborate as multiple teams to strengthen full supervision of the standardization of antiemetic drugs, reasonably select antiemetic drugs based on emetogenicity rating, and improve the compliance of doctors with the guidelines to ensure the safety, effectiveness, and cost-effective of patient medication.


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