Objective To utilize a comprehensive two-sample Mendelian randomized analysis for determining the causal relation-ship between immune cells and heart failure.Methods Immune cell data were collected from the genome-wide association analysis da-tabase,while the data of heart failure were obtained from the FinnGen database.The inverse variance weighted method,MR-Egger re-gression method,weighted median method,and weighted model method were employed to analyze the causal relationship between immune cells and heart failure.Comprehensive sensitivity analysis was utilized to verify the robustness,heterogeneity,and level pleiotropy of the results.The Stsiger test was applied to determine whether there was a reverse causal relationship between heart failure and immune cells.Results A total of 2557single nucleotide polymorphisms(SNP)were obtained from 731 immune cells.A total of 25 immunophenotypes were identified as having a causal function before the adjustment.After Bonferroni adjustment,only three results retained statistical signifi-cance.The inverse variance weighted analysis showed that there was a significant causal relationship between the absolute lymphocyte count and the increased risk of heart failure(HF)(OR=1.199,95％CI:1.104-1.302,P=1.70 × 10-5).The absolute count of T cells(OR=1.186,95％CI:1.095-1.284,P=2.84×10-5),and the absolute count of plasma-like dendritic cells(OR=1.137,95％CI:1.056-1.224,P=0.0007)were positively correlated with HF.The Stsiger test did not detect a causal relationship between heart failure and immune cells.Conclusion There exists a causal relationship between immune cells and the risk of heart failure.

BACKGROUND:Studies at home and abroad have shown that sarcopenia is closely related to metabolites.At present,the relationship between the latest 1400 blood metabolites and sarcopenia is still unknown.OBJECTIVE:To analyze the causal relationship between 1 400 metabolites and sarcopenia and its relevance with cardiovascular disease using Mendelian randomization.METHODS:Genome-wide association study(GWAS)data of sarcopenia-related characteristics(grip strength,limb muscle lean body mass,and walking speed)were obtained from the OPEN GWAS website as outcome data.A GWAS containing 1 400 metabolites was used as an exposure factor,and single nucleotide polymorphisms significantly associated with exposure factors were selected as instrumental variables.The causal association between 1 400 metabolites and sarcopenia was analyzed by"TwoSampleMR"and"gwasglue"packages of R software(V4.3.2).The research methods included inverse variance weighting,MR-Eggeer regression intercept,weighted median method,and simple mode.Heterogeneity,pleiotropic,sensitivity and other verification analysis were performed.Finally,reverse Mendelian randomization analysis was performed.RESULTS AND CONCLUSION:(1)The causal relationship between 1 400 serum metabolites and sarcopenia was analyzed by inverse variance weighting.The results showed that 1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate were protective factors,and the risk of disease decreased with the increase of metabolites(P＜0.01).(2)Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate were risk factors.With the increase of two unknown metabolites(X-12822 and X-15486),the degree of low grip strength of male hands increased.Similarly,with the increase of trans-3,4-methylene heptanoate,the risk of disease also increased(P＜0.01).(3)To conclude,1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate have inhibitory effects on sarcopenia.Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate can promote sarcopenia.This may be a new idea and new basis for sarcopenia research and treatment in the future.This study will also provide a reference for the study of the role of related metabolites in the Chinese population.

Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

OBJECTIVE To observe the effect of electroacupuncture(EA)preconditioning at Tianshu(ST25)and Neiguan(PC6)on cardiac function and UCP1/BMP3b signaling pathway in brown adipose tissue(BAT)in mice with acute myocardial infarc-tion(AMI),so as to explore the potential mechanism of EA at different acupoints in improving myocardial infarction.METHODS Healthy adult mice and BAT excision mice were selected as the research objects,and they were divided into sham operation group,model group,PC6 group,and ST25 group.After one week of adaptive feeding,the mice in the intervention group were pretreated with bilateral EA at PC6 or ST25 for 20 minutes,respectively,and the AMI model was established by ligating the left anterior descending branch of the coronary artery.In the BAT resection group,BAT resection of the scapular region was performed before EA,and the rest of the intervention remained the same as before.Echocardiography was used to detect the changes in cardiac function.TTC staining was used to observe the myocardial infarct size.ELISA was used to detect the serum levels of cTnT and BMP3b in each group.The qPCR was used to detect the relative expression of β3-AR,UCP1 and BMP3b mRNA in mouse BAT.The protein expression of BMP3b in BAT and p-Smad1/5 in the heart were detected by Western blot.RESULTS Compared with the sham operation group,the left ven-tricular EF and FS of the model group mice were decreased(P<0.001),the white infarct area was increased(P<0.001),the cTnT level in serum was increased(P<0.001),the mRNA expression levels of β3-AR,UCP1,and BMP3b in BAT were increased(P<0.05,P<0.01),and the protein expression of BMP3b was increased(P<0.01).The BMP3b content in serum was increased(P<0.001),and the protein expression of p-Smad1/5 in the heart was increased(P<0.01).Compared with the model group,the left ventricular EF and FS of mice in the ST25 and PC6 group were increased(P<0.001),the area of white infarction was reduced(P<0.001),and the cTnT level in serum was decreased(P<0.05,P<0.01).The mRNA contents of β3-AR,UCP1,and BMP3b in BAT of the ST25 group were significantly increased(P<0.05,P<0.01,P<0.001),the protein expression of BMP3b was increased(P<0.01),and the protein expression of p-Smad1/5 in the heart was increased(P<0.01),while there was no significant change in the PC6 group.After BAT resection,compared with the model group,the left ventricular EF and FS of the mice in the PC6 group were increased(P<0.001),the area of white infarction was reduced(P<0.001),and the cTnT in serum was decreased(P<0.001),while there was no significant change in the ST25 group;there was no significant change in the protein expression of p-Smad1/5 in the heart and the BMP3b content in the serum of the PC6 and ST25 groups.CONCLUSION EA pretreatment at either ST25 or PC6 acupoints can produce myocardial protective effects.The protective effect of ST25 may be through influencing the UCP1/BMP3b signaling path-way in BAT,while PC6 does not depend on this pathway.

Objective To investigate the neurovascular coupling(NVC)status in the acute phase of patients with minor ischemic stroke(MIS)or transient ischemic attack(TIA)due to intracranial large artery moderate-to-severe stenosis or occlusion using multimodal MRI techniques and to explore its correlation with quality of life(QoL).Methods This prospective,consecutive study enrolled patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion form the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,between June 2022 and October 2023.Recruit healthy subjects with matched age,sex,and handedness form the community during the same period.Patients were divided into left-sided involvement and right-sided involvement groups based on the affected side of the responsible vessel,while the healthy subjects were set as the healthy control group.Post-hoc power analysis was performed using G*Power 3.1 software.General characteristics(age,gender,body mass index,education level)were collected and compared across all three groups.Clinical data and QoL assessment were collected and compared between the two patient groups.Collected clinical data including type of cerebrovascular events(TIA,MIS),the National Institutes of Health stroke scale(NIHSS)score at admission,the responsible vessel(internal carotid artery,middle cerebral artery)and its side location,the degree of responsibility artery stenosis(moderate-severe stenosis[50%-99%stenosis rate],occlusion[100%stenosis rate]),the intracranial collateral circulation status(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASITN/SIR]collateral circulation grading),cerebrovascular risk factors(hypertension,diabetes,hyperlipidemia,smoking history),and the laboratory test indicators at admission(glycated hemoglobin,triglycerides,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,blood uric acid,blood homocysteine).QoL was assessed using the stroke impact scale(SIS),covering eight functional domains and a patient-reported overall recovery item.Multimodal MR data were acquired for all subjects.Whole-brain cerebral blood flow(CBF)images were generated using statistics parameter mapping 12(SPM 12)software,while regional homogeneity(ReHo)images were generated using DPABI software.The voxel-wise ratio of CBF to ReHo(CBF/ReHo)was calculated as the regional NVC parameter.Differences in regional NVC characteristics were compared between patient groups and the healthy control group.Correlations between NVC parameters and SIS scores within patient groups were explored.Results(1)A total of 38 patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion were included(26 males,12 females,aged 36-69 years,with mean age of[52±11]years),with 23 in the left-sided involvement group and 15 in the right-sided involvement group.Nineteen healthy subjects were included(10 males,9 females,aged 37-67 years,with mean age of[53±10]years).Post-hoc power analysis showed statistical power of 0.808 for comparing the left-sided involvement group with the healthy control group and 0.762 for comparing the right-sided involvement group with control group.(2)No statistically significant differences were found on gender,age,education level,or body mass index across the three groups(all P＞0.05).No statistically significant differences were observed on the type of cerebrovascular event,cerebrovascular risk factors,distribution of the responsible vessel,degree of stenosis in the responsible vessel,admission NIHSS score,or laboratory test results between the two patient groups(all P＞0.05).There were no statistically significant differences in the total SIS score and the scores of subscales between the two patient groups(all P＞0.05).(3)Compared with the healthy control group,the left-sided involvement group exhibited reduced CBF/ReHo values in the left superior and middle temporal gyri,supramarginal gyrus,middle and inferior frontal gyri,precentral gyrus,angular gyrus,postcentral gyrus,insula,and posterior cerebellar lobe(FDR-corrected,all P＜0.05).In the right-sided involvement group,reduced CBF/ReHo values were observed in the right supramarginal gyrus,right postcentral gyrus,inferior temporal gyrus,and insula(FDR-corrected,all P＜0.05).(4)Correlation analysis revealed that the SIS total score in the left-sided involvement group negatively correlated with CBF/ReHo values in the right inferior frontal gyrus(T=-5.91)and the right middle temporal gyrus(T=-6.65,FDR-corrected,both P＜0.05).The SIS subscale score for activities of daily living in the left-sided involvement group showed negative correlations with CBF/ReHo values in the right angular gyrus(T=-7.36),right medial superior frontal gyrus(T=-6.97),right orbitofrontal cortex(T=-8.99),and left thalamus(T=-7.51,FDR-corrected,all P＜0.05).No significant correlation was observed between the SIS total score and CBF/ReHo values in patients with right-sided involvement group.The SIS subscale for communication score in the right-sided involvement group correlated with CBF/ReHo in the left lingual gyrus(T=-12.15),left olfactory cortex(T=-7.68),and right anterior cingulate and paracingulate cortex(T=-9.46,FDR-corrected,all P＜0.05).Conclusions Patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion show abnormal NVC in the acute phase,especially those with left hemisphere involvement,who exhibit more extensive impairments.QoL in left-sided involvement patients is strongly linked to NVC in the right orbitofrontal cortex and right middle temporal gyrus.These findings require further validation in larger-scale studies.

BACKGROUND:The relationship between rheumatoid arthritis and coronary atherosclerosis has received extensive attention.Inflammation is related to rheumatoid arthritis and coronary atherosclerosis,indicating that there may be a common pathophysiological pathway between the two diseases.However,observational studies have not yet clarified the causal relationship.OBJECTIVE:To explore whether there is a causal relationship between rheumatoid arthritis and coronary atherosclerosis,as well as the potential causal relationship with 1 400 serum metabolites and 91 inflammatory factors through a Mendelian randomization analysis.METHODS:Coronary atherosclerosis data are from Finngen database,rheumatoid arthritis data are from IEU OpenGWAS database,serum metabolites data are from Canadian Longitudinal Study on Aging,Augsburg Cooperative Health Research and British Twin Project Research,and data of 91 inflammatory proteins are from research published in Nature Immunology in 2023.Mendelian randomization analysis was performed using data from genome-wide association studies,and causal effects were evaluated using inverse variance weighting,MR-Egger regression,weighted median,weighted model,and simple model methods,with inverse variance weighting being the primary analysis method.To enhance robustness,Cochran's Q-test MR-Egger intercept was used for sensitivity analysis.RESULTS AND CONCLUSION:(1)Inverse variance weighting results showed that rheumatoid arthritis was positively correlated with the increased relative risk of coronary atherosclerosis(odds ratio=1.002,95％confidence interval=1.001-1.003,P=0.003).There was no reverse causal relationship between coronary atherosclerosis and rheumatoid arthritis.In addition,96 serum metabolites and 9 inflammatory factors were found to have causal relationships with coronary atherosclerosis.There was a causal relationship between 51 serum metabolites and 7 inflammatory factors and rheumatoid arthritis.(2)This study provided epidemiological evidence between rheumatoid arthritis and coronary atherosclerosis,and emphasized the potential role of serum metabolites and inflammatory factors in the pathogenesis of these diseases.These findings may contribute to the development of new treatment strategies.Due to the limited inclusion of data from Asian populations,most contemporary studies used international databases and European population analyses.By collecting and analyzing the health data of European populations,it is conducive to a better understanding of the effects and potential role of Chinese medicine in Europe,and to further promote the practice of modern integration of Western and Chinese medicine.Meanwhile,through the comparative study with the European databases,it is possible to reveal the genetic differences and susceptibility to diseases among different populations,providing more dimensions and perspectives for global health research.

OBJECTIVE To observe the effect of electroacupuncture(EA)preconditioning at Tianshu(ST25)and Neiguan(PC6)on cardiac function and UCP1/BMP3b signaling pathway in brown adipose tissue(BAT)in mice with acute myocardial infarc-tion(AMI),so as to explore the potential mechanism of EA at different acupoints in improving myocardial infarction.METHODS Healthy adult mice and BAT excision mice were selected as the research objects,and they were divided into sham operation group,model group,PC6 group,and ST25 group.After one week of adaptive feeding,the mice in the intervention group were pretreated with bilateral EA at PC6 or ST25 for 20 minutes,respectively,and the AMI model was established by ligating the left anterior descending branch of the coronary artery.In the BAT resection group,BAT resection of the scapular region was performed before EA,and the rest of the intervention remained the same as before.Echocardiography was used to detect the changes in cardiac function.TTC staining was used to observe the myocardial infarct size.ELISA was used to detect the serum levels of cTnT and BMP3b in each group.The qPCR was used to detect the relative expression of β3-AR,UCP1 and BMP3b mRNA in mouse BAT.The protein expression of BMP3b in BAT and p-Smad1/5 in the heart were detected by Western blot.RESULTS Compared with the sham operation group,the left ven-tricular EF and FS of the model group mice were decreased(P<0.001),the white infarct area was increased(P<0.001),the cTnT level in serum was increased(P<0.001),the mRNA expression levels of β3-AR,UCP1,and BMP3b in BAT were increased(P<0.05,P<0.01),and the protein expression of BMP3b was increased(P<0.01).The BMP3b content in serum was increased(P<0.001),and the protein expression of p-Smad1/5 in the heart was increased(P<0.01).Compared with the model group,the left ventricular EF and FS of mice in the ST25 and PC6 group were increased(P<0.001),the area of white infarction was reduced(P<0.001),and the cTnT level in serum was decreased(P<0.05,P<0.01).The mRNA contents of β3-AR,UCP1,and BMP3b in BAT of the ST25 group were significantly increased(P<0.05,P<0.01,P<0.001),the protein expression of BMP3b was increased(P<0.01),and the protein expression of p-Smad1/5 in the heart was increased(P<0.01),while there was no significant change in the PC6 group.After BAT resection,compared with the model group,the left ventricular EF and FS of the mice in the PC6 group were increased(P<0.001),the area of white infarction was reduced(P<0.001),and the cTnT in serum was decreased(P<0.001),while there was no significant change in the ST25 group;there was no significant change in the protein expression of p-Smad1/5 in the heart and the BMP3b content in the serum of the PC6 and ST25 groups.CONCLUSION EA pretreatment at either ST25 or PC6 acupoints can produce myocardial protective effects.The protective effect of ST25 may be through influencing the UCP1/BMP3b signaling path-way in BAT,while PC6 does not depend on this pathway.

Objective To utilize a comprehensive two-sample Mendelian randomized analysis for determining the causal relation-ship between immune cells and heart failure.Methods Immune cell data were collected from the genome-wide association analysis da-tabase,while the data of heart failure were obtained from the FinnGen database.The inverse variance weighted method,MR-Egger re-gression method,weighted median method,and weighted model method were employed to analyze the causal relationship between immune cells and heart failure.Comprehensive sensitivity analysis was utilized to verify the robustness,heterogeneity,and level pleiotropy of the results.The Stsiger test was applied to determine whether there was a reverse causal relationship between heart failure and immune cells.Results A total of 2557single nucleotide polymorphisms(SNP)were obtained from 731 immune cells.A total of 25 immunophenotypes were identified as having a causal function before the adjustment.After Bonferroni adjustment,only three results retained statistical signifi-cance.The inverse variance weighted analysis showed that there was a significant causal relationship between the absolute lymphocyte count and the increased risk of heart failure(HF)(OR=1.199,95％CI:1.104-1.302,P=1.70 × 10-5).The absolute count of T cells(OR=1.186,95％CI:1.095-1.284,P=2.84×10-5),and the absolute count of plasma-like dendritic cells(OR=1.137,95％CI:1.056-1.224,P=0.0007)were positively correlated with HF.The Stsiger test did not detect a causal relationship between heart failure and immune cells.Conclusion There exists a causal relationship between immune cells and the risk of heart failure.

BACKGROUND:Studies at home and abroad have shown that sarcopenia is closely related to metabolites.At present,the relationship between the latest 1400 blood metabolites and sarcopenia is still unknown.OBJECTIVE:To analyze the causal relationship between 1 400 metabolites and sarcopenia and its relevance with cardiovascular disease using Mendelian randomization.METHODS:Genome-wide association study(GWAS)data of sarcopenia-related characteristics(grip strength,limb muscle lean body mass,and walking speed)were obtained from the OPEN GWAS website as outcome data.A GWAS containing 1 400 metabolites was used as an exposure factor,and single nucleotide polymorphisms significantly associated with exposure factors were selected as instrumental variables.The causal association between 1 400 metabolites and sarcopenia was analyzed by"TwoSampleMR"and"gwasglue"packages of R software(V4.3.2).The research methods included inverse variance weighting,MR-Eggeer regression intercept,weighted median method,and simple mode.Heterogeneity,pleiotropic,sensitivity and other verification analysis were performed.Finally,reverse Mendelian randomization analysis was performed.RESULTS AND CONCLUSION:(1)The causal relationship between 1 400 serum metabolites and sarcopenia was analyzed by inverse variance weighting.The results showed that 1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate were protective factors,and the risk of disease decreased with the increase of metabolites(P＜0.01).(2)Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate were risk factors.With the increase of two unknown metabolites(X-12822 and X-15486),the degree of low grip strength of male hands increased.Similarly,with the increase of trans-3,4-methylene heptanoate,the risk of disease also increased(P＜0.01).(3)To conclude,1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate have inhibitory effects on sarcopenia.Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate can promote sarcopenia.This may be a new idea and new basis for sarcopenia research and treatment in the future.This study will also provide a reference for the study of the role of related metabolites in the Chinese population.