Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low pe...Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.展开更多
Objective:Hypertension is a serious public health concern that is influenced by a variety of body composition parameters.This study examines the associations between body composition metrics and blood pressure(BP)in a...Objective:Hypertension is a serious public health concern that is influenced by a variety of body composition parameters.This study examines the associations between body composition metrics and blood pressure(BP)in a rural population,specifically how variations in body fat distribution and other metrics affect systolic blood pressure(SBP)and diastolic blood pressure(DBP).Methods:A cross-sectional study of 226 participants examined the relationships between body composition metrics—such as total body fat,visceral fat,and body mass index(BMI)—and BP.Correlation and regression analyses were used to assess these relationships.Results:The study found substantial positive correlations between visceral fat and total body fat with both SBP and DBP.Visceral fat was strongly connected with both SBP(r=0.145,P=0.030)and DBP(r=0.331,P<0.01),while total body fat was significantly correlated with DBP(r=0.268,P<0.01)but not SBP.Body composition variables explained 12.8% of the variance in SBP(R^(2)=0.128,P=0.001)and 15.0% in DBP(R^(2)=0.150,P<0.001).Conclusions:The study found substantial connections between body composition,particularly visceral and subcutaneous fat and systolic and DBP.Higher levels of visceral fat were linked to elevate BP.Body composition accounted for a significant amount of BP fluctuation.展开更多
Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the bl...Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.展开更多
While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the assoc...While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence.Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline,we employed structural equation modeling to assess the mediating effects of systolic(SBP)and diastolic(DBP)blood pressure.During the follow-up,2811 incident stroke cases were identified.A healthy lifestyle was significantly associated with a reduced risk of stroke,with SBP mediating 44.70%(β=-0.0014,95%confidence interval[CI]:-0.0016 to-0.0012)and DBP mediating 37.81%(β=-0.0012,95%CI:-0.0015 to-0.0009)of this association.The mediating effects were attenuated but remained significant for ischemic stroke(SBP:33.21%;DBP:27.24%).In conclusion,approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP.These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.展开更多
Sport-related concussion(SRC)and its potential neurological sequela represent an emerging global health concern,requiring improved recovery management and strategies for return-to-play(RTP)to enhance brain health in a...Sport-related concussion(SRC)and its potential neurological sequela represent an emerging global health concern,requiring improved recovery management and strategies for return-to-play(RTP)to enhance brain health in athletes.Given the dynamic and multifaceted nature of SRC recovery,the purpose of this review is to synthesize existing literature on post-SRC outcomes in adult athletes,and to outline the temporal trajectories of key recovery indicators(symptoms,cognitive function,blood biomarkers)across distinct recovery phases until resolution.In the acute phase of SRC(first 48 h),symptom scores and brain damage markers peaked immediately,while cognitive impairments and neuroinflammation emerged with a slight delay.Following the initial rise,brain damage marker concentrations rapidly dropped below baseline levels at approximately 48 h following SRC injury.During the early recovery phase,neuroinflammation and most cognitive alterations resolved after 3–5 days,though symptom burden and attention deficits persisted for up to 7 days.Despite prolonged alterations reported in some individuals,recovery markers typically returned to pre-injury levels in the transition phase(≤2 weeks),though mild attention deficits were detected up to 3 weeks,and TNF-α concentrations remained elevated throughout late recovery(>2 weeks).These results reveal distinct temporal discrepancies across recovery markers and emphasize that physiological disturbances can outlast symptom resolution,underscoring the need for both multimodal assessments and appropriately timed evaluations to accurately track recovery progression.Incorporating structured follow-ups at key time points,particularly beyond symptom resolution,may improve RTP decision-making and reduce the risk of premature return and long-term neurological consequences.展开更多
Accurate blood pressure(BP)monitoring is essential for preventing and managing cardiovascular disease.Advancements in materials science,medicine,flexible electronic,and artificial intelligence(AI)have enabled cuffless...Accurate blood pressure(BP)monitoring is essential for preventing and managing cardiovascular disease.Advancements in materials science,medicine,flexible electronic,and artificial intelligence(AI)have enabled cuffless,unobtrusive BP monitoring systems,offering an alternative to traditional sphygmomanometers.However,extending these advances to real-world cardiovascular care particularly in resource-limited settings remains challenging due to constraints in computational resources,power efficiency,and deployment scalability.This review presents a comprehensive synthesis of AI-enhanced wearable BP monitoring,emphasizing its potential for personalized,scalable,and accessible healthcare.We systematically analyze the end-to-end system architecture,from mechano-electric sensing principles and AI-based estimation models to edge-aware deployment strategies tailored for low-resource environments.We further discuss clinical validation metrics and implementation barriers and prospective strategies.To bridge lab-to-field translation,we propose an innovative"sensor-model-deployment-assessment"co-design framework.This roadmap highlights how AI-enhanced BP technologies can support proactive hypertension control and promote cardiovascular health equity on a global scale.展开更多
Objective:To explore the intervention effect of comprehensive perioperative blood glucose management on patients with diabetes complicated with cataract surgery.Method:A total of 68 patients in our hospital from July ...Objective:To explore the intervention effect of comprehensive perioperative blood glucose management on patients with diabetes complicated with cataract surgery.Method:A total of 68 patients in our hospital from July 2024 to July 2025 were selected and randomly divided into the experimental group and the control group,with 34 cases in each group.The control group received routine blood glucose management,while the experimental group,on this basis,implemented individualized intervention 3 days before the operation,real-time regulation during the operation,dynamic management 7 days after the operation,and self-management training.Result:The blood glucose control in the experimental group was more stable 7 days after the operation.The total incidence of complications(2.9%)was significantly lower than that in the control group(38.2%),and the average hospital stay(5.1±1.0 days)was shorter than that in the control group(7.3±1.4 days).One week after the operation,the proportions of uncorrected visual acuity and visual acuity≥0.6(67.6%)were both better than those of the control group(p<0.001).Conclusion:The whole-course management of perioperative blood glucose can enhance the stability of blood glucose control,reduce the risk of complications,shorten the length of hospital stay,promote visual recovery,and has high clinical promotion value.展开更多
Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabo...Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabolites mediating the associations ofα-diversity with blood pressure(BP)and BP variability(BPV).Methods Metagenomics and plasma targeted metabolomics were conducted on 523 Chinese participants from the MetaSalt study.The 24-hour,daytime,and nighttime BP and BPV were calculated based on ambulatory BP measurements.Linear mixed models were used to characterize the relationships betweenα-diversity(Shannon and Chao1 index)and BP indices.Mediation analyses were performed to assess the contribution of metabolites to the observed associations.The influence of key metabolites on hypertension was further evaluated in a prospective cohort of 2,169 participants.Results Gut microbial richness(Chao1)was negatively associated with 24-hour systolic BP,daytime systolic BP,daytime diastolic BP,24-hour systolic BPV,and nighttime systolic BPV(P<0.05).Moreover,26 metabolites were strongly associated with richness(Bonferroni P<0.05).Among them,four key metabolites(imidazole propionate,2-hydroxy-3-methylbutyric acid,homovanillic acid,and hydrocinnamic acid)mediated the associations between richness and BP indices(proportions of mediating effects:14.1%–67.4%).These key metabolites were also associated with hypertension in the prospective cohort.For example,each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent(OR[95%CI]=0.90[0.82,0.99];P=0.03)and incident hypertension(HR[95%CI]=0.83[0.71,0.96];P=0.01).Conclusion Our results suggest that gut microbial richness correlates with lower BP and BPV,and that certain metabolites mediate these associations.These findings provide novel insights into the pathogenesis and prevention of hypertension.展开更多
Genome-wide association study(GWAS)data are used to explore the associations between blood metabolites and 5 respiratory diseases:asthma,tuberculosis(TB),chronic obstructive pulmonary disease(COPD),cor pulmonale,and b...Genome-wide association study(GWAS)data are used to explore the associations between blood metabolites and 5 respiratory diseases:asthma,tuberculosis(TB),chronic obstructive pulmonary disease(COPD),cor pulmonale,and bronchitis.The main method of analysis used is the inverse-variance weighted(IVW)approach,complemented by several sensitivity analyses,including MR-Egger regression,the weighted median,the weighted mode,Cochran’s Q test,and the pleiotropy test.Additional directional tests,Meta-analysis and metabolic pathway analyses are conducted for deeper insights.3 metabolites showing significant causal relationships are identified.Catechol glucuronide levels as a protective factor have a positive causal relationship with asthma;the creatine to carnitine ratio has a negative causal relationship with COPD as a risk factor;and the adenosine 5’-diphosphate(ADP)to N-acetylglucosamine to N-acetylgalactosamine ratio as a protective factor has a positive causal relationship with bronchitis.Additionally,13 metabolites demonstrate strong causal relationships.Furthermore,we delineate 14 metabolic pathways related to the outcomes,including 6 associated with asthma,2 with TB,1 with COPD,4 with cor pulmonale,and 1 with bronchitis.A causal relationship between blood metabolites and 5 respiratory diseases has been established.The identified metabolites and pathways offer new insights into the underlying mechanisms of these diseases,necessitating further experimental validation.展开更多
The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an imper...The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an impermeable wall,safeguarding the CNS by excluding blood-derived molecules and circulating cells.However,this view has evolved.The BBB is now recognized as a dynamic interface that selectively regulates the exchange of signals,cells.展开更多
Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal var...Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal varying characteristics,remains poorly understood.Here,we collected cortical resting-state CBF in rats with left carotid artery blockage during occlusion–reperfusion,and measured the temporal variability and changes in laterality using a novel state-space method.This method was also applied to stroke EEG datasets to validate its effectiveness.After arterial occlusion,the left marginal motor,sensory,auditory,and visual cortices exhibited severe temporal variability impairments.The laterality analysis indicated that affected left regions showed inferior unilateral mean,inter-hemispheric transition probability,time fraction,and laterality duration,while the right side had a higher laterality time fraction and duration.These impairments recovered partially following blood flow restoration.Besides,the ischemic state-space metrics were positively correlated with the pre-occlusion baseline appearance.Stroke patients exhibited impaired temporal variability in the affected ischemic hemisphere.The state-space analysis revealed damaged CBF temporal variability during cerebral ischemia and predicted baseline-ischemia connections.展开更多
Multiple sclerosis(MS)is a chronic disorder of the central nervous system characterized by multifocal lesions where inflammation,demyelination,and neurodegeneration occur(Jakimovski et al.,2024).MS diagnosis primarily...Multiple sclerosis(MS)is a chronic disorder of the central nervous system characterized by multifocal lesions where inflammation,demyelination,and neurodegeneration occur(Jakimovski et al.,2024).MS diagnosis primarily relies on the demonstration of dissemination in time and space of the lesions based on clinical,magnetic resonance imaging(MRI),and cerebrospinal fluid assessments(Jakimovski et al.,2024).展开更多
Objective Patients with atherosclerotic cardiovascular disease(ASCVD)following percutaneous coronary intervention(PCI)are classified as very-high-risk individuals in cardiovascular disease(CVD)risk stratification.The ...Objective Patients with atherosclerotic cardiovascular disease(ASCVD)following percutaneous coronary intervention(PCI)are classified as very-high-risk individuals in cardiovascular disease(CVD)risk stratification.The distribution pattern of traditional Chinese medicine(TCM)syndromes in this patient population,as well as its association with blood lipid profiles and clinical prognosis,remains unclear.The present prospective cohort study aims to investigate these correlations,thereby providing insights to enrich the research fields.Methods We enrolled consecutive patients with ASCVD who underwent PCI at the Integrated Cardiology Unit of China-Japan Friendship Hospital between September 1,2020 and December 31,2022.Demographics and clinical characteristics,signs and symptoms defining each TCM syndrome,and fasting venous blood samples were collected at baseline and follow up or upon major adverse cardiovascular events(MACEs).We analyzed the correlation between TCM syndromes,blood lipid profiles,and MACEs,and developed a new joint prognostic model incorporating both TCM syndromes and blood lipids using logistic regression.The analyses were based on detailed baseline and one-year follow-up data.Results A per-protocol analysis was performed on 586 patients with complete data ultimately.During the one-year follow-up,174 patients(29.69%)experienced a MACE.We performed statistical analyses on comorbidities,medication,and biochemical indicators across groups defined by TCM syndrome differentiation.When comparing different TCM syndromes,no significant differences were found in age,body mass index(BMI),history of revascularization,comorbidities,family history of CVD,smoking or drinking,or statin intensity(P>0.05).Patients with intertwined phlegm and blood stasis syndrome exhibited significantly higher levels of total cholesterol(TC,5.27±1.18 mmol/L,P<0.001),triglyceride(TG,1.96±1.33 mmol/L,P=0.008),low-density lipoprotein cholesterol(LDL-C,3.35±0.79 mmol/L,P<0.001),and high-density lipoprotein cholesterol(HDL-C,1.24±0.81 mmol/L,P<0.001)compared with those with other TCM syndromes combined.A multivariable logistic regression model was constructed to predict MACEs.The model included TCM syndrome type[with intertwined phlegm and blood stasis as a predictor,adjusted odds ratio(OR)=1.413,95%confidence interval(CI):0.517–3.864,P=0.501],age(adjusted OR=0.97,95%CI:0.955–1.001,P=0.057),male gender(adjusted OR=0.698,95%CI:0.416–1.170,P=0.173),TC(adjusted OR=1.004,95%CI:0.513–1.965,P=0.990),and LDL-C(adjusted OR=5.825,95%CI:2.214–15.326,P<0.001).This model demonstrated good discriminatory ability for MACEs in post-PCI ASCVD patients[the area under the receiver operating characteristic(ROC)curve(AUC)=0.865,95%CI:0.816–0.914].Conclusion The intertwined phlegm and blood stasis TCM syndrome is associated with a distinct atherogenic lipid profile characterized by elevated levels of TC and LDL-C.The prognostic model that incorporates this TCM syndrome type along with conventional lipid parameters(TC and LDL-C)shows good discriminatory ability for predicting MACEs in ASCVD patients after PCI,underscoring the potential clinical utility of integrating TCM syndrome differentiation into CVD risk assessment.展开更多
OBJECTIVE:To explore the objective biological evidence for the classification and diagnosis of Traditional Chinese Medicine(TCM)syndromes in ankylosing spondylitis(AS)using multiomics analysis.METHODS:Patients with AS...OBJECTIVE:To explore the objective biological evidence for the classification and diagnosis of Traditional Chinese Medicine(TCM)syndromes in ankylosing spondylitis(AS)using multiomics analysis.METHODS:Patients with AS were categorized into kidney deficiency and blood stasis syndrome(SX group)and damp-heat stasis syndrome(SR group).Transcriptomic sequencing and quantitative plasma proteomics were performed on patients with AS and healthy volunteers.Multiomics integration was used to characterize the biological basis of AS with renal deficiency and blood stasis syndrome.Specific proteins were validated by quantitative reverse transcriptionpolymerase chain reaction(RT-q PCR)and enzymelinked immunosorbent assay(ELISA).RESULTS:Transcriptomic sequencing identified 31 significantly upregulated genes in patients with AS compared to healthy controls.These genes were primarily involved in tumor necrosis factor,interleukin-17,and nuclear factor kappa-B signaling pathways,as well as osteoblast differentiation and various viral infection pathways.Differentially expressed genes,including intercellular adhesion molecule 1(ICAM1),6-phosphofructo-2-kinase,cyclin-dependent kinase inhibitor 1A,interleukin 1 receptor antagonist,integrin alpha IIb,and myosin light chain 9 were more upregulated in the SX group than in the SR group.Quantitative proteomics identified 723 differential proteins associated with the disease and 788 differential proteins between the SX and SR groups.Notable proteins such as myeloperoxidase,cluster of differentiation 14,macrophage simulating 1(MST1),and Ras homolog enriched in brain may serve as characteristic proteins of the SX group.By integrating transcriptomic and proteomic data,45 associated differential molecules involved in platelet activation,pathogenic intestinal flora infection,glycolysis/gluconeogenesis,and T-cell receptor signaling pathways were identified in patients with AS compared to healthy controls.Additionally,ICAM1,MST1,C-X-C motif chemokine ligand 8(CXCL8),suppressor of cytokine signaling 3(SOCS3),and insulin-like growth factor binding protein 1(IGFBP1)were detected in TCM syndromes by RT-q PCR and ELISA,showing upregulation in AS renal deficiency and blood stasis syndromes,which is consistent with the proteomic and transcriptomic results.CONCLUSIONS:ICAM1,MST1,CXCL8,SOCS3,and IGFBP1 were identified as biomarkers of renal deficiency and blood stasis syndrome in AS.This study provides a biological basis for the differential diagnosis of TCM syndromes in AS,offering new insights into Chinese medicine evidence and more precise Chinese medicine treatments for AS.展开更多
In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflamma...In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.展开更多
Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellul...Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellular tau neurofibrillary tangles,leading to synaptic dysfunction,neuronal loss,and cognitive decline.These pathological changes can begin decades before clinical symptoms emerge,highlighting the critical need for early,accessible,and accurate diagnostic tools.展开更多
Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various phy...Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.展开更多
Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain ...Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.展开更多
Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse...Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.展开更多
Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile ...Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile based on 1468 blood samples from both human and mouse studies,which include bulk RNA sequencing(RNA-seq),microRNA-seq,and single-cell RNA-seq data.We developed a comprehensive analysis pipeline that conducted over 11 million comparisons and correlations to identify more than 20,000 blood features.With these findings,we established a blood RNA database related to Alzheimer’s disease,RNAs in Blood of AD(RBAD,http://www.bioinform.cn/RBAD/).Using RBAD,we initially validated well-established Alzheimer’s disease-related pathways,including olfactory transduction.We then observed a decrease in both the proportion and functionality of erythroid cells,likely attributed to their elevated CD45 levels and interactions with GZMK^(+)CD8^(+)T cells.Furthermore,we identified 449 blood RNAs linked to patients’overall survival,along with two mRNAs(H4C3 and CTU1)associated with cognitive decline.In summary,RBAD is the first web-based analysis platform dedicated to investigating blood RNA changes in Alzheimer’s disease,and provides valuable insights into potential peripheral biomarkers and pathogenic mechanisms related to Alzheimer’s disease.展开更多
基金supported by the NIH RF1 grant NS119477 jointly funded by NINDS and NIA(to RM).
文摘Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.
基金supported by Universitas Advent Indonesia(No.067/EKS-SU/V/24 and 389/KEPK-FIK.UNAI/EC/V/24)。
文摘Objective:Hypertension is a serious public health concern that is influenced by a variety of body composition parameters.This study examines the associations between body composition metrics and blood pressure(BP)in a rural population,specifically how variations in body fat distribution and other metrics affect systolic blood pressure(SBP)and diastolic blood pressure(DBP).Methods:A cross-sectional study of 226 participants examined the relationships between body composition metrics—such as total body fat,visceral fat,and body mass index(BMI)—and BP.Correlation and regression analyses were used to assess these relationships.Results:The study found substantial positive correlations between visceral fat and total body fat with both SBP and DBP.Visceral fat was strongly connected with both SBP(r=0.145,P=0.030)and DBP(r=0.331,P<0.01),while total body fat was significantly correlated with DBP(r=0.268,P<0.01)but not SBP.Body composition variables explained 12.8% of the variance in SBP(R^(2)=0.128,P=0.001)and 15.0% in DBP(R^(2)=0.150,P<0.001).Conclusions:The study found substantial connections between body composition,particularly visceral and subcutaneous fat and systolic and DBP.Higher levels of visceral fat were linked to elevate BP.Body composition accounted for a significant amount of BP fluctuation.
基金supported by the National Natural Science Foundation of China,No.U21A20400(to QW)the National Natural Science Foundation of China,No.82104560(to CL)+1 种基金the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,Nos.2024-JYB-JBZD-043(to CL),2022-JYB-JBZR-004(to XW)。
文摘Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82192900,82192901,82192904,81390540,and 91846303 to L.L.)the National Key Research and Development Program of China(Grant No.2016YFC0900500 to Y.G.)the Kadoorie Charitable Foundation in Hong Kong,and the Wellcome Trust in the UK(Grant/Award Nos.088158/Z/09/Z,104085/Z/14/Z,and 202922/Z/16/Z to Z.C.).
文摘While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence.Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline,we employed structural equation modeling to assess the mediating effects of systolic(SBP)and diastolic(DBP)blood pressure.During the follow-up,2811 incident stroke cases were identified.A healthy lifestyle was significantly associated with a reduced risk of stroke,with SBP mediating 44.70%(β=-0.0014,95%confidence interval[CI]:-0.0016 to-0.0012)and DBP mediating 37.81%(β=-0.0012,95%CI:-0.0015 to-0.0009)of this association.The mediating effects were attenuated but remained significant for ischemic stroke(SBP:33.21%;DBP:27.24%).In conclusion,approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP.These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.
文摘Sport-related concussion(SRC)and its potential neurological sequela represent an emerging global health concern,requiring improved recovery management and strategies for return-to-play(RTP)to enhance brain health in athletes.Given the dynamic and multifaceted nature of SRC recovery,the purpose of this review is to synthesize existing literature on post-SRC outcomes in adult athletes,and to outline the temporal trajectories of key recovery indicators(symptoms,cognitive function,blood biomarkers)across distinct recovery phases until resolution.In the acute phase of SRC(first 48 h),symptom scores and brain damage markers peaked immediately,while cognitive impairments and neuroinflammation emerged with a slight delay.Following the initial rise,brain damage marker concentrations rapidly dropped below baseline levels at approximately 48 h following SRC injury.During the early recovery phase,neuroinflammation and most cognitive alterations resolved after 3–5 days,though symptom burden and attention deficits persisted for up to 7 days.Despite prolonged alterations reported in some individuals,recovery markers typically returned to pre-injury levels in the transition phase(≤2 weeks),though mild attention deficits were detected up to 3 weeks,and TNF-α concentrations remained elevated throughout late recovery(>2 weeks).These results reveal distinct temporal discrepancies across recovery markers and emphasize that physiological disturbances can outlast symptom resolution,underscoring the need for both multimodal assessments and appropriately timed evaluations to accurately track recovery progression.Incorporating structured follow-ups at key time points,particularly beyond symptom resolution,may improve RTP decision-making and reduce the risk of premature return and long-term neurological consequences.
基金the Chinese University of Hong Kong for providing research resources and institutional support
文摘Accurate blood pressure(BP)monitoring is essential for preventing and managing cardiovascular disease.Advancements in materials science,medicine,flexible electronic,and artificial intelligence(AI)have enabled cuffless,unobtrusive BP monitoring systems,offering an alternative to traditional sphygmomanometers.However,extending these advances to real-world cardiovascular care particularly in resource-limited settings remains challenging due to constraints in computational resources,power efficiency,and deployment scalability.This review presents a comprehensive synthesis of AI-enhanced wearable BP monitoring,emphasizing its potential for personalized,scalable,and accessible healthcare.We systematically analyze the end-to-end system architecture,from mechano-electric sensing principles and AI-based estimation models to edge-aware deployment strategies tailored for low-resource environments.We further discuss clinical validation metrics and implementation barriers and prospective strategies.To bridge lab-to-field translation,we propose an innovative"sensor-model-deployment-assessment"co-design framework.This roadmap highlights how AI-enhanced BP technologies can support proactive hypertension control and promote cardiovascular health equity on a global scale.
文摘Objective:To explore the intervention effect of comprehensive perioperative blood glucose management on patients with diabetes complicated with cataract surgery.Method:A total of 68 patients in our hospital from July 2024 to July 2025 were selected and randomly divided into the experimental group and the control group,with 34 cases in each group.The control group received routine blood glucose management,while the experimental group,on this basis,implemented individualized intervention 3 days before the operation,real-time regulation during the operation,dynamic management 7 days after the operation,and self-management training.Result:The blood glucose control in the experimental group was more stable 7 days after the operation.The total incidence of complications(2.9%)was significantly lower than that in the control group(38.2%),and the average hospital stay(5.1±1.0 days)was shorter than that in the control group(7.3±1.4 days).One week after the operation,the proportions of uncorrected visual acuity and visual acuity≥0.6(67.6%)were both better than those of the control group(p<0.001).Conclusion:The whole-course management of perioperative blood glucose can enhance the stability of blood glucose control,reduce the risk of complications,shorten the length of hospital stay,promote visual recovery,and has high clinical promotion value.
基金supported by the National Science and Technology Major Program for Noncommunicable Chronic Diseases(2023ZD0503500)the National Natural Science Foundation of China(82030102,12126602,91857118)+1 种基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-010,2019-I2M-2-003)the National High Level Hospital Clinical Research Funding(2022-GSP-GG-1,2022-GSP-GG-2)。
文摘Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabolites mediating the associations ofα-diversity with blood pressure(BP)and BP variability(BPV).Methods Metagenomics and plasma targeted metabolomics were conducted on 523 Chinese participants from the MetaSalt study.The 24-hour,daytime,and nighttime BP and BPV were calculated based on ambulatory BP measurements.Linear mixed models were used to characterize the relationships betweenα-diversity(Shannon and Chao1 index)and BP indices.Mediation analyses were performed to assess the contribution of metabolites to the observed associations.The influence of key metabolites on hypertension was further evaluated in a prospective cohort of 2,169 participants.Results Gut microbial richness(Chao1)was negatively associated with 24-hour systolic BP,daytime systolic BP,daytime diastolic BP,24-hour systolic BPV,and nighttime systolic BPV(P<0.05).Moreover,26 metabolites were strongly associated with richness(Bonferroni P<0.05).Among them,four key metabolites(imidazole propionate,2-hydroxy-3-methylbutyric acid,homovanillic acid,and hydrocinnamic acid)mediated the associations between richness and BP indices(proportions of mediating effects:14.1%–67.4%).These key metabolites were also associated with hypertension in the prospective cohort.For example,each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent(OR[95%CI]=0.90[0.82,0.99];P=0.03)and incident hypertension(HR[95%CI]=0.83[0.71,0.96];P=0.01).Conclusion Our results suggest that gut microbial richness correlates with lower BP and BPV,and that certain metabolites mediate these associations.These findings provide novel insights into the pathogenesis and prevention of hypertension.
基金The National Natural Science Foundation of China-Regional Science Foundation Project“Research on constructing cell communication networks based on single-cell and spatial transcriptomics data”(62362062)The Multimodal Major Chronic Disease Prevention and Control Science and Engineering Key Laboratory Project of MIIT“Identification of novel drug targets for lung cancer via Mendelian randomization analysis based on blood proteomics”(MCD-2023-1-15).
文摘Genome-wide association study(GWAS)data are used to explore the associations between blood metabolites and 5 respiratory diseases:asthma,tuberculosis(TB),chronic obstructive pulmonary disease(COPD),cor pulmonale,and bronchitis.The main method of analysis used is the inverse-variance weighted(IVW)approach,complemented by several sensitivity analyses,including MR-Egger regression,the weighted median,the weighted mode,Cochran’s Q test,and the pleiotropy test.Additional directional tests,Meta-analysis and metabolic pathway analyses are conducted for deeper insights.3 metabolites showing significant causal relationships are identified.Catechol glucuronide levels as a protective factor have a positive causal relationship with asthma;the creatine to carnitine ratio has a negative causal relationship with COPD as a risk factor;and the adenosine 5’-diphosphate(ADP)to N-acetylglucosamine to N-acetylgalactosamine ratio as a protective factor has a positive causal relationship with bronchitis.Additionally,13 metabolites demonstrate strong causal relationships.Furthermore,we delineate 14 metabolic pathways related to the outcomes,including 6 associated with asthma,2 with TB,1 with COPD,4 with cor pulmonale,and 1 with bronchitis.A causal relationship between blood metabolites and 5 respiratory diseases has been established.The identified metabolites and pathways offer new insights into the underlying mechanisms of these diseases,necessitating further experimental validation.
基金supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number K02NS110973 and R01NS126498(to MAP).
文摘The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an impermeable wall,safeguarding the CNS by excluding blood-derived molecules and circulating cells.However,this view has evolved.The BBB is now recognized as a dynamic interface that selectively regulates the exchange of signals,cells.
基金supported by the National Natural Science Foundation of China(82250410380 and 62171101)the Natural Science Foundation of Sichuan Province(24NSFSC6257)the China MOST2030 Brain Project(2022ZD0208500).
文摘Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal varying characteristics,remains poorly understood.Here,we collected cortical resting-state CBF in rats with left carotid artery blockage during occlusion–reperfusion,and measured the temporal variability and changes in laterality using a novel state-space method.This method was also applied to stroke EEG datasets to validate its effectiveness.After arterial occlusion,the left marginal motor,sensory,auditory,and visual cortices exhibited severe temporal variability impairments.The laterality analysis indicated that affected left regions showed inferior unilateral mean,inter-hemispheric transition probability,time fraction,and laterality duration,while the right side had a higher laterality time fraction and duration.These impairments recovered partially following blood flow restoration.Besides,the ischemic state-space metrics were positively correlated with the pre-occlusion baseline appearance.Stroke patients exhibited impaired temporal variability in the affected ischemic hemisphere.The state-space analysis revealed damaged CBF temporal variability during cerebral ischemia and predicted baseline-ischemia connections.
基金supported by Italian Ministry for Health(RF-2011-02349698,RF-2018-12367731)(to CF).
文摘Multiple sclerosis(MS)is a chronic disorder of the central nervous system characterized by multifocal lesions where inflammation,demyelination,and neurodegeneration occur(Jakimovski et al.,2024).MS diagnosis primarily relies on the demonstration of dissemination in time and space of the lesions based on clinical,magnetic resonance imaging(MRI),and cerebrospinal fluid assessments(Jakimovski et al.,2024).
基金Capital Health Development Scientific Research Project(2020-2-4064)National Key Research and Development Program of China(2018YFC2002502).
文摘Objective Patients with atherosclerotic cardiovascular disease(ASCVD)following percutaneous coronary intervention(PCI)are classified as very-high-risk individuals in cardiovascular disease(CVD)risk stratification.The distribution pattern of traditional Chinese medicine(TCM)syndromes in this patient population,as well as its association with blood lipid profiles and clinical prognosis,remains unclear.The present prospective cohort study aims to investigate these correlations,thereby providing insights to enrich the research fields.Methods We enrolled consecutive patients with ASCVD who underwent PCI at the Integrated Cardiology Unit of China-Japan Friendship Hospital between September 1,2020 and December 31,2022.Demographics and clinical characteristics,signs and symptoms defining each TCM syndrome,and fasting venous blood samples were collected at baseline and follow up or upon major adverse cardiovascular events(MACEs).We analyzed the correlation between TCM syndromes,blood lipid profiles,and MACEs,and developed a new joint prognostic model incorporating both TCM syndromes and blood lipids using logistic regression.The analyses were based on detailed baseline and one-year follow-up data.Results A per-protocol analysis was performed on 586 patients with complete data ultimately.During the one-year follow-up,174 patients(29.69%)experienced a MACE.We performed statistical analyses on comorbidities,medication,and biochemical indicators across groups defined by TCM syndrome differentiation.When comparing different TCM syndromes,no significant differences were found in age,body mass index(BMI),history of revascularization,comorbidities,family history of CVD,smoking or drinking,or statin intensity(P>0.05).Patients with intertwined phlegm and blood stasis syndrome exhibited significantly higher levels of total cholesterol(TC,5.27±1.18 mmol/L,P<0.001),triglyceride(TG,1.96±1.33 mmol/L,P=0.008),low-density lipoprotein cholesterol(LDL-C,3.35±0.79 mmol/L,P<0.001),and high-density lipoprotein cholesterol(HDL-C,1.24±0.81 mmol/L,P<0.001)compared with those with other TCM syndromes combined.A multivariable logistic regression model was constructed to predict MACEs.The model included TCM syndrome type[with intertwined phlegm and blood stasis as a predictor,adjusted odds ratio(OR)=1.413,95%confidence interval(CI):0.517–3.864,P=0.501],age(adjusted OR=0.97,95%CI:0.955–1.001,P=0.057),male gender(adjusted OR=0.698,95%CI:0.416–1.170,P=0.173),TC(adjusted OR=1.004,95%CI:0.513–1.965,P=0.990),and LDL-C(adjusted OR=5.825,95%CI:2.214–15.326,P<0.001).This model demonstrated good discriminatory ability for MACEs in post-PCI ASCVD patients[the area under the receiver operating characteristic(ROC)curve(AUC)=0.865,95%CI:0.816–0.914].Conclusion The intertwined phlegm and blood stasis TCM syndrome is associated with a distinct atherogenic lipid profile characterized by elevated levels of TC and LDL-C.The prognostic model that incorporates this TCM syndrome type along with conventional lipid parameters(TC and LDL-C)shows good discriminatory ability for predicting MACEs in ASCVD patients after PCI,underscoring the potential clinical utility of integrating TCM syndrome differentiation into CVD risk assessment.
基金Supported by National Natural Science Foundation of China:to Explore the Molecular Mechanism of Treating Ankylosing Spondylitis by Invigorating Kidney and Activating Blood from the Regulation of T helper 17 Cells Differentiation and Migration by Histone Histone H3 Lysine 27 Trimethylation(No.81873292)Science and Technology Innovation Project of China Academy of Chinese Medical Sciences:Evaluation of Curative Effect and Molecular Mechanism of Shenqiangji Decoction in the Treatment of Ankylosing Spondylitis by Standard Control and Intervention in the Imaging Progress of Spinal Spondylitis(No.CI2021A01506)High Level Chinese Medical Hospital Promotion Project:Research and Development of Traditional Chinese Medicine Preparation for Treating Ankylosing Spondylitis with Danxian Bushen Qiangji Granules(No.HLCMHPP2023049)。
文摘OBJECTIVE:To explore the objective biological evidence for the classification and diagnosis of Traditional Chinese Medicine(TCM)syndromes in ankylosing spondylitis(AS)using multiomics analysis.METHODS:Patients with AS were categorized into kidney deficiency and blood stasis syndrome(SX group)and damp-heat stasis syndrome(SR group).Transcriptomic sequencing and quantitative plasma proteomics were performed on patients with AS and healthy volunteers.Multiomics integration was used to characterize the biological basis of AS with renal deficiency and blood stasis syndrome.Specific proteins were validated by quantitative reverse transcriptionpolymerase chain reaction(RT-q PCR)and enzymelinked immunosorbent assay(ELISA).RESULTS:Transcriptomic sequencing identified 31 significantly upregulated genes in patients with AS compared to healthy controls.These genes were primarily involved in tumor necrosis factor,interleukin-17,and nuclear factor kappa-B signaling pathways,as well as osteoblast differentiation and various viral infection pathways.Differentially expressed genes,including intercellular adhesion molecule 1(ICAM1),6-phosphofructo-2-kinase,cyclin-dependent kinase inhibitor 1A,interleukin 1 receptor antagonist,integrin alpha IIb,and myosin light chain 9 were more upregulated in the SX group than in the SR group.Quantitative proteomics identified 723 differential proteins associated with the disease and 788 differential proteins between the SX and SR groups.Notable proteins such as myeloperoxidase,cluster of differentiation 14,macrophage simulating 1(MST1),and Ras homolog enriched in brain may serve as characteristic proteins of the SX group.By integrating transcriptomic and proteomic data,45 associated differential molecules involved in platelet activation,pathogenic intestinal flora infection,glycolysis/gluconeogenesis,and T-cell receptor signaling pathways were identified in patients with AS compared to healthy controls.Additionally,ICAM1,MST1,C-X-C motif chemokine ligand 8(CXCL8),suppressor of cytokine signaling 3(SOCS3),and insulin-like growth factor binding protein 1(IGFBP1)were detected in TCM syndromes by RT-q PCR and ELISA,showing upregulation in AS renal deficiency and blood stasis syndromes,which is consistent with the proteomic and transcriptomic results.CONCLUSIONS:ICAM1,MST1,CXCL8,SOCS3,and IGFBP1 were identified as biomarkers of renal deficiency and blood stasis syndrome in AS.This study provides a biological basis for the differential diagnosis of TCM syndromes in AS,offering new insights into Chinese medicine evidence and more precise Chinese medicine treatments for AS.
基金part of the EU consortium DCog Plast ‘Diet Cognition and Plasticity” funded by the Joint Programming Initiative “A Health Diet for a Healthy Life”(JPI-HDHL) via the BMWFW (BMWFW-10.420/0009-WF/V/3c/2015 and the Medical Research Council UK:MR/N030087/1)(to LA and ST)supported by the PMU-FFF Research Fund (A-16/01/019-AIG)+9 种基金BA by the PMU-Research and Innovation Fund (PMU-RIF)(project 2023-PRE-008-Altendorfer)supported by the Center for Urban Mental Healthby Alzheimer Nederlandthe Zon MW Program Mechanisms Of DEMentia (MODEM)by the Gravitation program iCNS of the Dutch Research Council (NWO)supported by Grant PID2020-114921RB-C21Maria de Maeztu Unit of Excellence grant CEX2021-001234-M funded by MCIU/AEI/and CIBERFESCB16/10/00269, from the Instituto de Salud Carlos III all of them by “ERDF A way of making Europe”the Generalitat de Catalunya’s Agency AGAUR of 2021SGR00687ICREA Award
文摘In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.
文摘Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellular tau neurofibrillary tangles,leading to synaptic dysfunction,neuronal loss,and cognitive decline.These pathological changes can begin decades before clinical symptoms emerge,highlighting the critical need for early,accessible,and accurate diagnostic tools.
基金funded by the Entrusted service project of Shaanxi Administration of Traditional Chinese Medicine(ZYJXG-L23001)2023 Sanqin Talent Special Support Program Innovation and Entrepreneurship Team Project,and Sci-Tech Innovation Talent System Construction Program of Shaanxi University of Chinese Medicine(2023).
文摘Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.
文摘Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.
基金supported by the National Natural Science Foundation of China,Nos. 32260196 (to JY), 81860646 (to ZY) and 31860274 (to JY)a grant from Yunnan Department of Science and Technology,Nos. 202101AT070251 (to JY), 202201AS070084 (to ZY), 202301AY070001-239 (to JY), 202101AZ070001-012, and 2019FI016 (to ZY)。
文摘Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.
基金supported by Research and Innovation Foundation of Wuhan Asia General Hospital,No.2022KYCX1-B10(to FH)the Natural ScienceFoundation of Hubei Province,No.2023AFB550(to FH)+2 种基金the National Natural Science Foundation of China,Nos.32400554(to FH),82371444(to YZ)theGuiding Project of the Scientific Research Program of the Department of Education of Hubei Province,No.B2021016(to FH)the Natural Science Foundationof Hubei Province,No.2024AFB853(to QW).
文摘Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile based on 1468 blood samples from both human and mouse studies,which include bulk RNA sequencing(RNA-seq),microRNA-seq,and single-cell RNA-seq data.We developed a comprehensive analysis pipeline that conducted over 11 million comparisons and correlations to identify more than 20,000 blood features.With these findings,we established a blood RNA database related to Alzheimer’s disease,RNAs in Blood of AD(RBAD,http://www.bioinform.cn/RBAD/).Using RBAD,we initially validated well-established Alzheimer’s disease-related pathways,including olfactory transduction.We then observed a decrease in both the proportion and functionality of erythroid cells,likely attributed to their elevated CD45 levels and interactions with GZMK^(+)CD8^(+)T cells.Furthermore,we identified 449 blood RNAs linked to patients’overall survival,along with two mRNAs(H4C3 and CTU1)associated with cognitive decline.In summary,RBAD is the first web-based analysis platform dedicated to investigating blood RNA changes in Alzheimer’s disease,and provides valuable insights into potential peripheral biomarkers and pathogenic mechanisms related to Alzheimer’s disease.
