OBJECTIVE: To explore the potential causal relationship between intervertebral disc degeneration and certain autoimmune diseases. METHODS: Genome-wide association study (GWAS) data of 5 autoimmune diseases were obtained from large-scale GWAS databases. Data on internal vertebral disc degeneration (IVDD) were derived from the FinnGen consortium, which included 294, 770 controls and 41, 669 cases. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to investigate the potential causal relationship between the 5 autoimmune diseases and IVDD. Multiple analytical methods were adopted, including MR methods such as inverse variance weighting(IVW), MR-Egger, weighted median, weighted mode, and simple mode. Cochran's Q test, leave-one-out analysis, and MR-Egger intercept test were conducted to assess heterogeneity, robustness, and pleiotropy. For the robustness of the results, MR-PRESSO was used to detect outliers, and MR analysis was re-conducted after removing the outliers. RESULTS: The MR analysis results showed that there might be a bidirectional causal relationship between ankylosing spondylitis(AS) and IVDD:AS on IVDD, OR=1.038, 95%CI (1.024, 1.053), P=0.000;and IVDD on AS, OR=2.117, 95%CI(1.065, 4.207), P=0.032. There might be a positive correlation between IVDD and rheumatoid arthritis(RA) as well as systemic lupus erythematosus(SLE):IVDD on RA, OR=1.184, 95%CI(1.071, 1.309), P=0.001;and IVDD on SLE, OR=1.678, 95%CI(1.187, 2.372), P=0.003. There was no significant correlation between ulcerative colitis(UC), autoimmune thyroiditis(ATD) and IVDD. After removing outliers by MR-PRESSO and re-conducting MR analysis, the results did not change qualitatively. Sensitivity analysis indicated that the results were robust to potential sources of bias. CONCLUSION AS and IVDD may be risk factors for each other, and IVDD may be a potential risk factor for RA and SLE. These findings provide a basis for guiding the prevention and combined diagnosis and treatment of IVDD, AS, RA, and SLE, while the specific underlying mechanisms still require further experimental basic research.
Humans ; Intervertebral Disc Degeneration/etiology* ; Mendelian Randomization Analysis ; Autoimmune Diseases/complications* ; Genome-Wide Association Study ; Spondylitis, Ankylosing/genetics* ; Arthritis, Rheumatoid/genetics*

Aim To investigate the effects of endur-ance exercise(EE)on rats following cerebral ischemi-a/reperfusion injury(CI/RI)and to explore its rela-tionship with the Mas signaling pathway.Methods Seventy-two adult male SD rats were randomly divided into four groups(n=18 each):sham group,model group,EE group(group E),and A779 pretreatment group(group A).The CI/RI model was established u-sing middle cerebral artery occlusion method Rats in both group E and group A underwent regular running for four weeks before model preparation,while rats in group A were injected with A779 30 minutes before model preparation.The cognitive function of rats was evaluated using the Neurological Disability Score(NDS)and Morris water maze test.After intravenous injection of Evans blue(EB)for one hour,the rats were euthanized,and brain tissues were collected to measure the infarction volume,EB content,ROS con-tent,and the percentage of apoptotic neurons of the hippocampal CA1 region.The protein expression relat-ed to the Mas pathway was detected by Western blot.Results Compared with the model group,the learning and memory ability as well as the neurological function in group E exhibited a significant improvement(P＜0.05).Both the cerebral infarction volume and the ap-optotic neuron percentage in the ischemic hippocampal CA1 region showed a significant reduction in group E(P＜0.05).The ROS content along with the EB con-tent in the brain tissue significantly decreased in group E(P＜0.05).Furthermore,the expressions of Mas/PKA/CREB/UCP2 pathway related proteins were sig-nificantly enhanced in group E(P＜0.05).However,the Mas receptor antagonist A779 significantly inhibited these neurological effects(P＜0.05).Conclusion EE may inhibit oxidative stress and alleviate CI/RI in rats by activating the Mas/PKA/CREB/UCP2 signaling pathway.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Objective:To explore the hemodynamic characteristics of the middle cerebral artery (MCA) in atherosclerotic stenosis using four-dimensional flow (4D Flow) MRI, and combining high-resolution magnetic resonance vessel wall imaging (HR VW-MRI) to analyze the relationship between hemodynamics and the degree of stenosis, as well as the morphological characteristics of plaques.Methods:The study was a cross-sectional study. A total of 24 patients with middle cerebral artery(MCA) M1 atherosclerotic stenosis and 10 age and sex matched healthy controls (HC group) were prospectively recruited from September 2018 to March 2021 at Beijing Tiantan Hospital, Capital Medical University. All subjects underwent MRI examination. The hemodynamic of MCA were collected by 4D Flow MRI, and the hemodynamic parameters of proximal and distal MCA stenosis were calculated by blood flow post-processing software, including average blood flow rate (FR avg), average blood flow velocity (V avg), peak blood flow velocity (V pk), time average wall shear stress (TAWSS), minimum wall shear stress (WSS min) and oscillatory shear index (OSI). The differences in hemodynamic parameters among the proximal and distal ends of MCA stenosis and the HC group were compared using one-way ANOVA or Kruskal-Wallis H test. The stenosis rate and characteristics of MCA plaque were analyzed by HR VW-MRI, including remodeling index (RI), normalized wall index (NWI) and plaque length. Pearson or Spearman correlation analysis was used to explore the correlation between stenosis rate and hemodynamic parameters. Taking the stenosis rate as the control variable, partial correlation analysis was used to explore the correlation between plaque morphological characteristics and hemodynamic parameters. Results:There were statistically significant differences in FR avg, V avg, V pk, TAWSS, OSI, WSS min among the proximal and distal stenosis of MCA and HC groups ( P<0.05). The proximal end of the MCA stenosis had significantly higher FR avg, V avg, TAWSS and WSS min than those of the distal end of the stenosis ( P<0.01). The FR avg, V avg, V pk, TAWSS, and WSS min in the distal end of MCA stenosis were lower than those in the HC group, while the OSI was higher than that in the HC group ( P<0.01). The correlation analysis results showed that the MCA proximal V pk ( r=-0.425, P=0.027) and distal V pk ( r=-0.538, P=0.004) were negatively correlated with the diameter stenosis rate. When the stenosis rate was taken as the control factor, in the MCA proximal stenosis, V avg ( r=0.553, P=0.003), TAWSS ( r=0.543, P=0.004) and WSS min ( r=0.547, P=0.004) were positively correlated with RI, proximal OSI was negatively correlated with RI ( r=-0.492, P=0.011), and was positively correlated with the plaque length ( r=0.437, P=0.026). At the distal end of the stenosis, V pk was negatively correlated with NWI ( r=-0.556, P=0.003), OSI was negatively correlated with RI ( r=-0.511, P=0.008), NWI ( r=-0.390, P=0.049). TAWSS was positively correlated with RI ( r=0.393, P=0.047). Conclusions:The 4D Flow MRI demonstrates characteristic hemodynamic changes in the proximal and distal ends of the stenotic MCA. The local hemodynamic characteristics of the stenotic MCA are correlated with plaque morphological parameters, including lumen stenosis, plaque load, and RI. It suggests an interaction between the occurrence and development of MCA plaque and local hemodynamic changes.

Purpose To explore the characteristics of gray matter(GM)volume changes in migraine patients using 7T MRI and voxel-based morphometry(VBM).Materials and Methods This prospective study enrolled 30 migraine patients and 41 age-and gender-matched healthy controls from Beijing Tiantan Hospital,Capital Medical University between November 2023 and November 2024.All participants underwent 7T MRI with 3D T1-weighted magnetization-prepared two rapid gradient-echo(MP2RAGE)sequences for structural brain imaging.VBM analysis was performed to quantify GM,white matter,cerebrospinal fluid and total brain volumes,followed by calculations of their relative percentages.The difference in GM volume between the two groups was compared to identify brain regions with characteristic GM volume changes in migraine patients.And the correlation between these characteristic GM volume alterations and clinical scales was analyzed.Results Migraine patients exhibited significantly lower total GM volume compared to healthy controls(t=2.096,P=0.040),while no group differences were observed in white matter or cerebrospinal fluid volumes(t=0.980,0.151;P=0.330,0.880).VBM analysis revealed reduced GM volume in the left orbitofrontal cortex(t=4.301,P=0.022),left hippocampus(t=5.226,P=0.006)and left parahippocampal gyrus(t=3.960,P=0.040)in the migraine group.Negative correlations were identified between:left orbitofrontal cortex GM volume and headache duration(r=-0.506,P=0.008),left hippocampal GM volume and patient health questionnaire-9 scores(r=-0.620,P=0.003),and left parahippocampal GM volume and visual analogue scale scores(r=-0.449,P=0.019).Conclusion VBM analysis based on 7T MP2RAGE data demonstrates characteristic GM volume reductions in the left orbitofrontal cortex,left hippocampus and left parahippocampal gyrus in migraine patients,with these structural alterations significantly correlate with depressive symptoms and headache burden.The observed microstructural abnormalities may reflect underlying pathophysiological mechanisms related to pain processing,emotional regulation and long-term disease burden in migraine.

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.

Objective To explore the effect of modified Buzhong Yiqi decoction(MBZYQ)on thyroid function in rats with Hashimoto's thyroiditis(HT)by regulating the Toll-like receptor 2(TLR2)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway.Methods The HT rat model was constructed.The successfully modeled rats were divided into the HT group,L-MBZYQ,M-MBZYQ,H-MBZYQ(intragastric administration of 11.35,22.70,and 45.40 g/kg MBZYQ granules,respectively),and the MBZYQ+Pam3CSK4 group(intragastric administration of 45.40 g/kg MBZYQ granules+intraperitoneal injection of 20 μg TLR2 agonist Pam3CSK4),with 10 rats in each group.Another 10 normally raised rats were selected as the control group.The pathological changes of thyroid tissues and the apoptosis of thyroid tissue cells in each group were observed by HE staining and TUNEL staining respectively.The expressions of serum thyroglobulin antibody(TGAb),thyroid peroxidase antibody(TPOAb),free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH),interleukin-17(IL-17),and interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the protein expression of TLR2,MyD88 and NF-κB in thyroid tissues.Results The pathological damage of thyroid tissues in the L-MBZYQ,M-MBZYQ and H-MBZYQ groups was alleviated.The apoptosis rate of cells,the expressions of TGAb,TPOAb,TSH,IL-17,TLR2,MyD88 and NF-κB were lower than those in the HT group,while the expressions of FT3,FT4 and IL-10 were higher than those in the HT group.Moreover,the degree of decrease or increase in the M-MBZYQ and H-MBZYQ groups was greater than that in the L-MBZYQ group,and the changes in the H-MBZYQ group were greater than those in the M-MBZYQ group(P<0.05).The pathological damage of thyroid tissue in the MBZYQ+Pam3CSK4 group was further aggravated.The apoptosis rate of cells,the expressions of TGAb,TPOAb,TSH,IL-17,TLR2,MyD88 and NF-κB were higher than those in the H-MBZYQ group,while the expressions of FT3,FT4 and IL-10 were lower than those in the H-MBZYQ group(P<0.05).Conclusion MBZYQ can protect the thyroid function of HT rats,and its mechanism of action may be achieved by inhibiting the TLR2/MyD88/NF-κB signaling pathway.

Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.

Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.

Objective To explore the effect of modified Buzhong Yiqi decoction(MBZYQ)on thyroid function in rats with Hashimoto's thyroiditis(HT)by regulating the Toll-like receptor 2(TLR2)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway.Methods The HT rat model was constructed.The successfully modeled rats were divided into the HT group,L-MBZYQ,M-MBZYQ,H-MBZYQ(intragastric administration of 11.35,22.70,and 45.40 g/kg MBZYQ granules,respectively),and the MBZYQ+Pam3CSK4 group(intragastric administration of 45.40 g/kg MBZYQ granules+intraperitoneal injection of 20 μg TLR2 agonist Pam3CSK4),with 10 rats in each group.Another 10 normally raised rats were selected as the control group.The pathological changes of thyroid tissues and the apoptosis of thyroid tissue cells in each group were observed by HE staining and TUNEL staining respectively.The expressions of serum thyroglobulin antibody(TGAb),thyroid peroxidase antibody(TPOAb),free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH),interleukin-17(IL-17),and interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the protein expression of TLR2,MyD88 and NF-κB in thyroid tissues.Results The pathological damage of thyroid tissues in the L-MBZYQ,M-MBZYQ and H-MBZYQ groups was alleviated.The apoptosis rate of cells,the expressions of TGAb,TPOAb,TSH,IL-17,TLR2,MyD88 and NF-κB were lower than those in the HT group,while the expressions of FT3,FT4 and IL-10 were higher than those in the HT group.Moreover,the degree of decrease or increase in the M-MBZYQ and H-MBZYQ groups was greater than that in the L-MBZYQ group,and the changes in the H-MBZYQ group were greater than those in the M-MBZYQ group(P<0.05).The pathological damage of thyroid tissue in the MBZYQ+Pam3CSK4 group was further aggravated.The apoptosis rate of cells,the expressions of TGAb,TPOAb,TSH,IL-17,TLR2,MyD88 and NF-κB were higher than those in the H-MBZYQ group,while the expressions of FT3,FT4 and IL-10 were lower than those in the H-MBZYQ group(P<0.05).Conclusion MBZYQ can protect the thyroid function of HT rats,and its mechanism of action may be achieved by inhibiting the TLR2/MyD88/NF-κB signaling pathway.