Association of cumulative resting heart rate exposure with rapid renal function decline:a prospective cohort study with 27,564 older adults

OBJECTIVE To evaluate the prospective association between cumulative resting heart rate(cumRHR)and rapid renal function decline(RRFD)in a cohort of individuals aged 60 and older.METHODS In the Tianjin Chronic Kidney Disease Cohort Study,the individuals who underwent three consecutive physical examinations between 2014 and 2017,with estimated glomerular filtration rate(eGFR)greater than 60 mL/min per 1.73 m2 and aged 60 years or older were enrolled.A total of 27,564 patients were prospectively followed up from January 1,2017 to December 31,2020.The 3-year cumRHR was calculated.The primary outcome was RRFD,defined as an annualized decline in eGFR of 5 mL/min per 1.73 m2 or greater.Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders.RESULTS During a median follow-up of 3.2 years,a total of 4,347(15.77%)subjects developed RRFD.In fully-adjusted models,compared with the lowest quartile of cumRHR,the odds ratio(OR)for the highest was 1.44(1.28–1.61),P<0.001.Furthermore,each 1-standard deviation(27.97 beats/min per year)increment in cumRHR was associated with a 17%(P<0.001)increased risk of RRFD,with a linear positive correlation(P for non-linear=0.803).Participants with a 3-year cumRHR≥207(beats/min)*year(equivalent to≥69 beats/min per year in 3 years)were found to be at a higher risk of RRFD.CONCLUSIONS The cumRHR is significantly associated with a higher risk of RRFD among older adults.These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

Metabolomic Analysis of Serum Glycerophospholipid Levels in Eosinophilic and Neutrophilic Asthma

Objective To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. Methods Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ≥ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ≥ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. Results The serum lysophosphatidylglycerol level was significantly higher in the group with ≥ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ≥ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ≥ 71% and the group with sputum neutrophils < 71%. Conclusion Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.

Risk Factors and Management of Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy:Single-center Experience

Pancreatic fistula(PF)remains the most frequent complication after pan­creaticoduodenectomy(PD).This study was undertaken to explore the risk factors of postoperative PF following PD and discuss the management of PF in our center.A single-center respective study,involving 241 patients who underwent PD between September 2015 and June 2018,was conducted.Differences in the demographic data,preoperative,intraoperative and postoperative variables between the group with PF[International Study Group on Pancreatic Surgery(ISGPS)grade B/C]and the group without PF(no PF and ISGPS grade BL)were evaluated.The diagnosis and grading of PF were in strict accordance with ISGPS.Risk factors were analyzed by univariate analysis and multivariate logistic regression analysis.The results showed that postoperative PF occurred in 50(20.7%)of the patients;25(10.4%)patients had a PF type BL,46(19.1%)patients developed a PF type B and 4(1.6%)had a PF type C.Univariate analysis showed that fasting blood glucose(P=0.02),pancreatic texture(P<0.001)and pancreatic duct diameter(P=0.01)were correlated with PF.Multivariate logistic regression analysis identified one independent risk factor for postoperative PF:soft pancreatic texture(OR=3.251,P=0.002).Among the cases,there were three postoperative deaths,giving a 60-day hospital mortality rate of 1.2%(3/241),and the mortality related to PF was 4.0%(2/50).One of the patients died from multiple organ failure caused by postoperative abdominal hemorrhage.In conclusion,soft pancreatic texture is an independent risk factor for PF.Surgeons should be well aware of this risk factor when performing a PD.

Effect of auricular acupoint sticking and pressing on postoperative pain of patients with mixed hemorrhoids:A Meta-analysis

Objective:To systematically evaluate the application effect of auricular acupuncture in postoperative analgesia in patients with mixed hemorrhoids.Methods:We searched Chinese Biomedical Literature Database,CNKI,WanFang,PubMed,Embase,and The Cochrane Library to collect randomized controlled trials about auricular acupuncture on Postoperative patients with mixed hemorrhoids.According to the inclusion criteria and exclusion criteria screening literature.RevMan 5.3 software was used for meta-analysis.Results:A total of 20 articles and 21 studies were included,including 1999 patients after mixed hemorrhoids.The control group was treated with routine nursing analgesia.The experimental group was treated with auricular acupressure beans based on the control group.The meta-analysis showed that the pain relief rate of the experimental group was better than that of the control group[OR=2.84,95%CI(2.12,3.80),P<0.05].Subgroup analysis showed that the application of auricular acupressure after milligan morgan was superior to the control group in the analgesic effect[OR=3.68,95%CI(2.62,5.18),P<0.05],but it is not yet possible to apply auricular acupoint pressing to relieve pain after Stapler hemorrhoidectomy(P>0.05).The pain scores of 24 hours and 48 hours after operation in the experimental group were lower than those of the control group,indicating that auricular acupoint sticking can relieve the pain after operation.The improvement of the postoperative anal margin edema was better in the experimental group than in the control group,24 h[SMD=-1.99,95%CI(-2.84,-1.14),P<0.05],48 h[SMD=-1.92,95%CI(-2.72,-1.11),P<0.05].The adverse reactions were lower than the control group.Conclusion:The application of ear acupoint pressure pea after external exfoliation of mixed hemorrhoids can improve the analgesic effect and reduce the symptoms of postoperative anal edge edema,and the price is low,the operation is convenient,and the side effects are few.It is recommended to be popularized in clinical practice.

Serum biomarkers in evaluation and management of idiopathic pulmonary fibrosis

Despite there has greater understanding of the pathophysiology in idiopathic pulmonary fibrosis,idiopathic pulmonary fibrosis still remains a challenge in clinical practice and translational research due to its heterogeneity.Improvements in molecular techniques have identified potential pathways and targets for diagnosis and therapeutic intervention.Several types of idiopathic pulmonary fibrosis biomarkers such as KL-6,SP-A,SP-D,MMP7 and other potential ones have been studied extensively.In addition,many studies have confirmed that levels of some tumor markers such as CA 19-9,CA 15-3,CEA,CA 125,CYFRA 21-1 are useful for idiopathic pulmonary fibrosis.The present study focuses on serum biomarkers including tumor markers to provide an overview on the current roles of these biomarkers in the setting of diagnosis,prediction as well as response to therapy in idiopathic pulmonary fibrosis.

Fructose and metabolic diseases: too much to be good

Excessive consumption of fructose,the sweetest of all naturally occurring carbohydrates,has been linked to worldwide epidemics of metabolic diseases in humans,and it is considered an independent risk factor for cardiovascular diseases.We provide an overview about the features of fructose metabolism,as well as potential mechanisms by which excessive fructose intake is associated with the pathogenesis of metabolic diseases both in humans and rodents.To accomplish this aim,we focus on illuminating the cellular and molecular mechanisms of fructose metabolism as well as its signaling effects on metabolic and cardiovascular homeostasis in health and disease,highlighting the role of carbohydrate-responsive element–binding protein in regulating fructose metabolism.

Metabolic Control ofγδT Cell Function

Metabolic change is associated with cell activities,such as signal transduction,cell differentiation,and cell cycle.In the pathogenesis of autoimmune diseases,abnormal activation of T cells is often accompanied by changes in their metabolism.Conversely,the changes of metabolites can also regulate the proliferation,differentiation,and function of T cells.As a bridge between innate and adaptive immune responses,γδT cells have unique biological characteristics and functions.However,the immunometabolic mechanism ofγδT cells has been a novel field for research in recent years.In this review,we summarize the influence of metabolic pathways and nutrients onγδT cell function,and metabolic features ofγδT cell subsets,which may provide new insights in interventions targetingγδT cells in disease control.

Immune‑Ageing Evaluation of Peripheral T and NK Lymphocyte Subsets in Chinese Healthy Adults

Ageing is often accompanied with a decline in immune system function,resulting in immune ageing.Numerous studies have focussed on the changes in different lymphocyte subsets in diseases and immunosenescence.The change in immune phenotype is a key indication of the diseased or healthy status.However,the changes in lymphocyte number and phenotype brought about by ageing have not been comprehensively analysed.Here,we analysed T and natural killer(NK)cell subsets,the phenotype and cell differentiation states in 43,096 healthy individuals,aged 20–88 years,without known diseases.Thirty-six immune parameters were analysed and the reference ranges of these subsets were established in different age groups divided into 5-year intervals.The data were subjected to random forest machine learning for immune-ageing modelling and confirmed using the neural network analysis.Our initial analysis and machine modelling prediction showed that na.ve T cells decreased with ageing,whereas central memory T cells(Tcm)and effector memory T cells(Tem)increased cluster of differentiation(CD)28-associated T cells.This is the largest study to investigate the correlation between age and immune cell function in a Chinese population,and provides insightful differences,suggesting that healthy adults might be considerably influenced by age and sex.The age of a person's immune system might be different from their chronological age.Our immune-ageing modelling study is one of the largest studies to provide insights into‘immune-age’rather than‘biological-age’.Through machine learning,we identified immune factors influencing the most through ageing and built a model for immune-ageing prediction.Our research not only reveals the impact of age on immune parameter differences within the Chinese population,but also provides new insights for monitoring and preventing some diseases in clinical practice.

PD-L1 is a direct target of cancer-FOXP3 in pancreatic ductal adenocarcinoma(PDAC),and combined immunotherapy with antibodies against PD-L1 and CCL5 is effective in the treatment of PDAC

High expression of PD-L1 marks the poor prognosis of pancreatic ductal adenocarcinomas(PDAC).However,the regulatory mechanism of PD-L1 remains elusive.We recently reported that cancer Forkhead box protein 3(Cancer-FOXP3 or C-FOXP3)promoted immune evasion of PDAC by recruiting Treg cells into PDAC via upregulation of CCL5.In this study,we confirmed that PD-L1 was overexpressed in PDAC samples from two independent cohorts of patients with radical resection.Moreover,C-FOXP3 was colocalized and correlated with the expression of PD-L1 in tumor cells at the mRNA and protein levels,and this finding was confirmed by the The Cancer Genome Atlas(TCGA)database.Chromatin immunoprecipitation(ChIP)revealed that C-FOXP3 directly bound to the promoter region of PD-L1 in pancreatic cancer cells.Furthermore,overexpression of C-FOXP3 activated the luciferase reporter gene under the control of the PD-L1 promoter.However,mutation of the binding motif-a completely reversed the luciferase activity.In addition,C-FOXP3-induced upregulation of PD-L1 effectively inhibited the activity of CD8+T cells.Based on our recent finding that the CCL-5 antibody achieved a better response to PDAC models with high C-FOXP3 levels,we further demonstrated that the PD-L1 antibody strengthened the antitumor effect of CCL-5 blockade in xenograft and orthotopic mouse models with high C-FOXP3 levels.In conclusion,C-FOXP3 directly activates PD-L1 and represents a core transcription factor that mediates the immune escape of PDAC.Combined blockade of PD-L1 and CCL-5 may provide an effective therapy for patients with PDAC that have high C-FOXP3 levels.

The molecular mechanisms supporting the homeostasis and activation of dendritic epidermal T cell and its role in promoting wound healing

The epidermis is the outermost layer of skin and the first barrier against invasion.Dendritic epidermal T cells(DETCs)are a subset ofT cells and an important component of the epidermal immune microenvironment.DETCs are involved in skin wound healing,malignancy and autoim-mune diseases.DETCs secrete insulin-like growth factor-1 and keratinocyte growth factor for skin homeostasis and re-epithelization and release inflammatory factors to adjust the inflammatory microenvironment of wound healing.Therefore,an understanding of their development,activation and correlative signalling pathways is indispensable for the regulation of DETCs to accelerate wound healing.Our review focuses on the above-mentioned molecular mechanisms to provide a general research framework to regulate and control the function of DETCs.

A novel role of LRP5 in tubulointerstitial fibrosis through activating TGF-β/Smad signaling

Previous studies by us and others demonstrated that activation of Wnt/β-catenin signaling plays a pathogenic role in chronic kidney diseases(CKD).Wnt co-receptor LRP5 variants are reported to associate with autosomal dominant polycystic kidney disease;but their exact roles in this disease and renal fibrosis have not been explored.Here,we observed the upregulation of LRP5 in the renal tubules of both type 1 and type 2 diabetic models and of an obstructive nephropathy model.In the obstructed kidneys,Lrp5 knockout significantly ameliorated tubulointerstitial fibrosis and tubular injury without changing Wnt/β-catenin signaling.Instead,decreased levels of TGF-β1 and TGF-βreceptors(TβRs)were detected in Lrp5 knockout kidneys,followed by attenuated activation and nuclear translocation of Smad2/3 in the renal tubules,suggesting a regulatory effect of LRP5 on TGF-β/Smad signaling.In consistent with this hypothesis,LRP5 overexpression resulted in enhanced TGF-β/Smad signaling activation in renal tubule epithelial cells.Furthermore,LRP5 was co-immunoprecipitated with TβRI and TβRII,and its extracellular domain was essential for interacting with TβRs and for its pro-fibrotic activity.In addition to stabilizing TβRs,LRP5 increased the basal membrane presentation and TGF-β1-induced internalization of these receptors.Notably,TGF-β1 also induced LRP5 internalization.These findings indicate that LRP5 promotes tubulointerstitial fibrosis,at least partially,via direct modulation of TGF-β/Smad signaling,a novel,Wnt-independent function.

Cold-induced Yes-associated-protein expression through miR-429 mediates the browning of white adipose tissue

Targeting the white-to-brown fat conversion is important for developing potential strategies to counteract metabolic diseases;yet the mechanisms are not fully understood.Yes-associated-protein(YAP),a transcription co-activator,was demonstrated to regulate adipose tissue functions;however,its effects on browning of subcutaneous white adipose tissue(sWAT)are unclear.We demonstrated that YAP was highly expressed in cold-induced beige fat.Mechanistically,YAP was found as a target gene of miR-429,which downregulated YAP expression in vivo and in vitro.In addition,miR-429 level was decreased in cold-induced beige fat.Additionally,pharmacological inhibition of the interaction between YAP and transcriptional enhanced associate domains by verteporfin dampened the browning of sWAT.Although adipose tissue-specific YAP overexpression increased energy expenditure with increased basal uncoupling protein 1 expression,it had no additional effects on the browning of sWAT in young mice.However,we found age-related impairment of sWAT browning along with decreased YAP expression.Under these circumstances,YAP overexpression significantly improved the impaired WAT browning in middle-aged mice.In conclusion,YAP as a regulator of sWAT browning,was upregulated by lowering miR-429 level in cold-induced beige fat.Targeting the miR-429-YAP pathway could be exploited for therapeutic strategies for age-related impairment of sWAT browning.

NIR-activated nanosystems with self-modulated bacteria targeting for enhanced biofilm eradication and caries prevention

The efficacious delivery of antimicrobial drugs to intractable oral biofilms remains a challenge due to inadequate biofilm penetration and lack of pathogen targeting.Herein,we have developed a microenvironment-activated poly(ethylene glycol)(PEG)-sheddable nanoplatform to mediate targeted delivery of drugs into oral biofilms for the efficient prevention of dental caries.The PEGylated nanoplatform with enhanced biofilm penetration is capable of deshielding the PEG layer under slightly acidic conditions in a PEG chain length-dependent manner to re-expose the bacteria-targeting ligands,thereby facilitating targeted codelivery of ciprofloxacin(CIP)and IR780 to the bacteria after accumulation within biofilms.The nanoplatform tends to induce bacterial agglomeration and suffers from degradation in the acidic oral biofilm microenvironment,triggering rapid drug release on demand around bacterial cells.The self-modulating nanoplatform under near-infrared(NIR)irradiation accordingly displays greatly augmented potency in oral biofilm penetration and disruption compared with drugs alone.Topical oral treatment with nanoplatforms involving synergetic pharmacological and photothermal/photodynamic trinary therapy results in robust biofilm dispersion and efficacious suppression of severe tooth decay in rats.This versatile nanoplatform can promote local accumulation and specific drug transport into biofilms and represents a new paradigm for targeted drug delivery for the management of oral biofilm-associated infections.

White-light upconversion emission of lanthanide double-doped oxide nanoparticles via defect state luminescence of ZnO

The white upconversion luminescence （UCL） of upconversion nanoparticles （UCNPs） is mainly made up of the color red, green and blue. Interestingly, the white-light-emitting UCNPs can be obtained via a complex method of tridoping lanthanide ions such as Yb^3＋, Er^3＋, and Tm^3＋. We herein report that an excellent white UCL can be obtained from Yb/Tm double-doped ZnO. In this system, the blue and red UCL-emissions around 475 and 652 nm originate from ^1G4→^3H6 and ^1G4→^3F4 transition of Tm^3＋, respectively, and the green one can be attributed to the defect states （oxygen va- cancies） luminescence （DSL） of the ZnO host. Meanwhile, the fine nanostructure of ZnO：Yb/Tm is prepared by adjusting the concentration of OH-. Particularly, the one dimentional pencil-shaped nanorods with high aspect ratio achieve a strong green DSL emission due to the high concentration of oxygen vacancy. The oxygen vacancy defects play an irreplaceable role in affecting the intensities of blue and red UCL by acting as the intermediate state in the energy transfer process. More importantly, we demonstrate that the DSL and UCL can be combined into systems, paving a new road for obtaining the white UCL emission.

The role of caveolae in endothelial dysfunction

Caveolae,the specialized cell-surface plasma membrane invaginations which are abundant in endothelial cells,play critical roles in regulating various cellular processes,including cholesterol homeostasis,nitric oxide production,and signal transduction.Endothelial caveolae serve as a membrane platform for compartmentalization,modulation,and integration of signal events associated with endothelial nitric oxide synthase,ATP synthaseβ,and integrins,which are involved in the regulation of endothelial dysfunction and related cardiovascular diseases,such as atherosclerosis and hypertension.Furthermore,these dynamic microdomains on cell membrane are modulated by various extracellular stimuli,including cholesterol and flow shear stress.In this brief review,we summarize the critical roles of caveolae in the orchestration of endothelial function based on recent findings as well as our work over the past two decades.

Increased Soluble Epoxide Hydrolase Activity Positively Correlates with Mortality in Heart Failure Patients with Preserved Ejection Fraction:Evidence from Metabolomics

Epoxyeicosatrienoic acids(EETs)have pleiotropic endogenous cardiovascular protective effects and can be hydrolyzed to the corresponding dihydroxyeicosatrienoic acids by soluble epoxide hydrolase(sEH).Heart failure with preserved ejection fraction(HFpEF)has shown an increased prevalence and worse prognosis over the decades.However,the role of sEH activ-ity in HFpEF remains unclear.We enrolled 500 patients with HFpEF and 500 healthy controls between February 2010 and March 2016.Eight types of sEH-related eicosanoids were measured according to target metabolomics,and their correlation with clinical endpoints was also analyzed.The primary endpoint was cardiac mortality,and the secondary endpoint was a composite of cardiac events,including heart failure(HF)readmission,cardiogenic hospitalization,and all-cause mortal-ity.Furthermore,the effect of sEH inhibitors on cardiac diastolic function in HFpEF was investigated in vivo and in vitro.Patients with HFpEF showed significantly enhanced EET degradation by the sEH enzyme compared with healthy controls.More importantly,sEH activity was positively correlated with cardiac mortality in patients with HFpEF,especially in older patients with arrhythmia.A consistent result was obtained in the multiple adjusted models.Decreased sEH activity by the sEH inhibitor showed a significant effective effect on the improvement of cardiac diastolic function by ameliorating lipid disorders in cardiomyocytes of HFpEF mouse model.This study demonstrated that increased sEH activity was associated with cardiac mortality in patients with HFpEF and suggested that sEH inhibition could be a promising therapeutic strategy to improve diastolic cardiac function.Clinical trial identifier:NCT03461107(https://clini caltr ials.gov).

Early intervention with Di-Dang Decoction prevents macrovascular fibrosis in diabetic rats by regulating the TGF-β1/Smad signalling pathway

Macroangiopathy is a complication of Type II Diabetes Mellitus(T2 DM),which is mainly caused by fibrosis of blood vessels.Using T2 DM rat models,we investigated whether the traditional Chinese medicine,Di-Dang Decoction(DDD),exhibited antifibrotic actions on great vessels.T2 DM rats were randomly divided into non-intervention group,early-,middle-,late-stage DDD intervention groups and control groups,including pioglitazone group and aminoguanidine group.After administration of DDD to T2 DM rats at different times,we detected the amount of extracellular matrix(ECM)deposition in the thoracic aorta.The results showed that early-stage intervention with DDD could effectively protect great vessels from ECM deposition.Considering that TGF-β1 is the master regulator of fibrosis,we further validated at the molecular level that,compared to middle-and late-stage intervention with DDD,early-stage intervention with DDD could significantly decrease the expression levels of factors related to the activated TGF-β1/Smad signalling pathway,as well as the expression levels of downstream effectors including CTGF,MMP and TIMP family proteins,which were directly involved in ECM remodelling.Therefore,early-stage intervention with DDD can reduce macrovascular fibrosis and prevent diabetic macroangiopathy.

Commutative regulation between endothelial NO synthase and insulin receptor substrate 2 by microRNAs

Endothelial NO synthase (eNOS) expression is regulated by a number of transcriptional and post-transcriptional mechanisms, but the effects of competing endogenous RNAs (ceRNAs) on eNOS mRNA and the underlying mechanisms are still unknown. Our bioinformatic analysis revealed three highly expressed eNOS-targeting miRNAs (miR-15b, miR-16, and miR-30b) in human endothelial cells (ECs). Among the 1103 mRNA targets of these three miRNAs, 15 mRNAs share a common disease association with eNOS. Gene expression and correlation analysis in patients with cardiovascular diseases identified insulin receptor substrate 2 (IRS2) as the most correlated eNOS-ceRNA. The expression levels of eNOS and IRS2 were coincidentally increased by application of laminar shear but reduced with eNOS or IRS2 siRNA transfection in human ECs, which was impeded by Dicer siRNA treatment. Moreover, luciferase reporter assay showed that these three miRNAs directly target the 3′UTR of eNOS and IRS2. Overexpression of these three miRNAs decreased, whereas inhibition of them increased, both mRNA and protein levels of eNOS and IRS2. Functionally, silencing eNOS suppressed the Akt signal pathway, while IRS2 knockdown reduced NO production in ECs. Thus, we identified eNOS and IRS2 as ceRNAs and revealed a novel mechanism explaining the coincidence of metabolic and cardiovascular diseases.

Programmed nanoparticle-loaded microparticles for effective antigen/adjuvant delivery

A microscale vaccine containing SiO_(2)nanoparticles loaded in CaC〇3 microparticles was constructed using the co-precipitation method.The antigen ovalbumin(OVA)was covalently conjugated with SiO_(2)nanoparticles,and these nanoparticles and CpG were co-encapsulated into CaCO_(3)microparticles,generating a vaccine with a size of approximately 5.2μm.Scanning electron microscopy(SEM),energy-dispersive X-ray(EDX),elemental mapping,and Fourier transform infrared(FTIR)analyses confirmed the successful preparation of the microscale vaccine;the vaccine had good storage stability without sustained antigen release,and negligible cytotoxicity to dendritic cells(DCs)and macrophages.Compared to SiO_(2)nanoparticles,the microscale vaccine can significantly improve antigen/adjuvant uptake.DCs internalized the entire microscale vaccine into lysosomes via macropinocytosis,and an increase in antigen endo/lysosomal escape was observed by confocal User scanning microscopy(CLSM).Specifically,DCs pulsed with the vaccine were fully mature,expressing high levels of costimulatory molecules(CD40,CD80,and CD86),MHCⅡ,and MHCⅠand secreting high levels of proinflammatory cytokines(IL-12,TNF-α,IL-1β,and IL-6).In addition,the vaccine had good in vivo biocompatibility,could protect the antigen from rapid degradation,and increased the retention time in lymph nodes.SiO_(2)nanoparticles-in-CaCO_(3)microparticles were an excellent carrier for antigen and adjuvant delivery.Hopefully,this study can provide some information on the design of microscale carriers for vaccine delivery systems.