Objective : To explore the effects of the antihypertensive drug Amlodipine on calcium influx and autoph- agy in human podocytes ( HPC) ． Methods : HPC cells were routinely cultured in vitro． HPC cells were treated with angiotensin Ⅱ ( Ang Ⅱ ) ，the L-type Ca2 + blocker Amlodipine alone or in combination．The Ca2 + imaging system was used to detect the transient changes in the intracellular Ca2 + flux of HPC cells in real time after drug treatment．Western blot was employed to detect the changes in the ratio of autophagy marker proteins LC3B-Ⅱ/ LC3B-Ⅰ , and the expression levels of Beclin-1，P62，as well as apoptosis-related proteins Bcl-2 and Bax．Flow cytometry was used to detect the number of Fluo-4AM positive cells at 488 nm to analyze the level of intracellular Ca2 + influx in HPC cells．Lyso-Tracker Green live cell staining was applied to analyze the fluorescence intensity of lysosomes．Flow cytometry was also used to detect the apoptosis rate of HPC cells． Results : Compared with the control group，in the Ang Ⅱ group，the transient Ca2 + flux and the number of Fluo-4AM positive cells increased significantly (P＜0. 001) ．The ratio of autophagy marker proteins LC3B-Ⅱ/ LC3B-Ⅰ (P＜0. 001) and the pro- tein expression of Beclin-1 (P＜0. 01) decreased significantly，while the expression of P62 increased (P＜0. 01) ． The fluorescence intensity of lysosomes weakened (P＜0. 05) ，the apoptosis rate increased (P＜0. 0001) ，the ex- pression of apoptosis-related protein Bcl-2 decreased (P ＜0. 01 ) ，and the protein level of Bax increased (P < 0. 001) ．Compared with the control group，in the Amlodipine group，the number of Fluo-4AM positive cells de- creased significantly (P＜0. 001) ，the ratio of LC3B-Ⅱ/ LC3B-Ⅰ (P＜0. 001) and the protein expression of Bec- lin-1 (P＜0. 001) increased，the protein expression of P62 decreased (P＜0. 05) ，the fluorescence intensity of ly- sosomes enhanced (P＜0. 01) ，the apoptosis rate decreased (P＜0. 01) ，the protein expression of Bcl-2 increased (P＜0. 001) ，and the protein level of Bax decreased (P＜0. 001) ．Compared with the Ang Ⅱ group，in the Ang Ⅱ + Amlodipine group，the number of Fluo-4AM positive cells decreased significantly (P＜0. 001) ，the ratio of LC3B-Ⅱ/ LC3B-Ⅰ (P＜0. 01) and the protein expression of Beclin-1 increased (P＜0. 05) ，the protein level of P62 decreased (P＜0. 01) ，the fluorescence intensity of lysosomes increased (P ＜0. 05) ，the apoptosis rate de- creased (P＜0. 001) ，the protein expression of Bcl-2 increased (P ＜0. 001 ) ，and the protein level of Bax de- creased (P＜0. 001) ． Conclusion Amlodipine inhibits calcium influx，promotes autophagy and inhibits apoptosis in human podocytes，which is useful in preventing the development of hypertensive nephropathy．

Objective : To explore the therapeutic effect of extracellular vesicles(EVs) of Aspergillus flavus(A. flavus) on A. flavus infection. Methods: The EVs of A. flavus were isolated using ultracentrifugation and detected/identified by nanoparticle tracking analysis(NTA). Quantitative real-time PCR(qRT-PCR) and enzyme-linked immunosorbent assay(ELISA) kits were used to assess the effect of A. flavus EVs on the polarization of bone marrowderived macrophages(BMDMs) and the expression levels of several cytokines,including tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-6(IL-6),and interleukin-10(IL-10). The Galleria mellonella(G.mellonella) infection model was constructed. Three concentration groups of A. flavus EVs(0. 2,2,and 20 μg/larvae) were set as the experimental groups,and PBS was used as the control group for the infection model.Meanwhile,three forms of negative control groups were established,including the PBS group,the pierced controlgroup, and the negative control group. The therapeutic effect of A. flavus EVs on A. flavus infection was evaluated by the survival rate of the G. mellonella infection models. Results: The particle size of A. flavus EVs ranged from 20 to550 nm. A. flavus EVs could polarize BMDMs into both M1 and M2 phenotypes and induce the production of cytokines,including TNF-α,IFN-γ,IL-6,and IL-10. The results of the G. mellonella infection model showed that A.flavus EVs could improve the survival rate of G. mellonella after A. flavus infection. Conclusion The EVs produced by A. flavus can promote the expression of both pro-inflammatory and anti-inflammatory cytokines in BMDMs,induce M1 polarization and M2 polarization of BMDMs,and increase the survival rate of G. mellonella after A. flavus infection.

The Keap1-Nrf2 pathway has been shown to be an important defense mechanism against oxidative stress, which may be an effective therapeutic strategy for many diseases. The research progresses on Keap1-Nrf2 pathway in inflammatory diseases were mainly reviewed. The basic components and activation mechanism of Keap1-Nrf2 pathway were introduced. The relationship between Keap1-Nrf2 pathway and the crosstalk between NF-κB pathway and HO-1 pathway, the expression of inflammatory mediators and enzymes, and inflammatory bodies were expounded. Natural product-derived inhibitors, small molecule inhibitors targeting Keap1-Nrf2 pathway and their clinical progress were introduced, and the potential application value of Keap1-Nrf2 pathway in the treatment of inflammation was discussed.

Objective:To investigate the molecular markers involved in death related to acute myocardial infarction (AMI) and provide new targets for early intervention.Methods:Consecutive patients who hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from January 2017 to December 2021 and diagnosed with AMI were enrolled. The clinical factors and markers associated with in-hospital death after AMI were analyzed. In addition, patients diagnosed with AMI hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from September 2022 to April 2023 were enrolled. We prospectively analyzed the plasma protein of death related to AMI via Olink Precision Proteomics based on proximity extension assay (PEA) technology.Results:In the retrospective study, 2 325 patients with AMI were analyzed, including 75 patients in the in-hospital death group and 2 250 subjects in the survival group. The overall mortality rate during hospitalization was 3.23% (75/2325). The patients in the death group were older: 72 (64, 80) years vs. 63 (55, 71) years. And Interleukin-6 (IL-6), hypersensitive C-reactive protein (Hs-CRP), leukocyte counts and neutrophil counts were markedly higher in the death group than those in the survival group: 69.0 (26.7, 136.6) ng/L vs. 18.2 (9.4, 36.5) ng/L, 45.7 (28.7, 50.5) mg/L vs. 5.5 (2.0, 17.2) mg/L, 12.0 (9.8, 14.1) ×10 9/L vs. 8.9 (7.2, 11.2) × 10 9/L, 9.8 (7.8, 12.1) ×10 9/L vs. 6.5(4.7, 8.8) ×10 9/L ( P<0.01). In this prospective study, 86 patients with AMI were analyzed. 61 proteins including Insulin-like growth factor-binding protein 1, 2 (IGFBP-1, IGFBP-2), Chitotriosidase-1 (CHIT1), Complement component C1q receptor (CD93) were independently associated with in-hospital death related to AMI ( P<0.05). The differential proteins were mainly enriched in inflammatory response, cell adhesion, cytokine signaling pathway and apoptosis. Moreover, 22 proteins including Urokinase plasminogen activator surface receptor (U-PAR), Trefoil factor 3 (TFF3), Perlecan (PLC), Growth differentiation factor 15 (GDF-15), Junctional adhesion molecule A (JAM-A) were plotted according to a logistic regression model, and the area under the curve (AUC) was more than 0.9, showing the high accuracy in predicting in-hospital death after AMI. Conclusions:Molecular markers of the inflammatory response, cell adhesion, cell growth and apoptosis might be involved in death related to AMI, which provides new targets for early intervention.

Objective To provide an efficient,reliable,and easily manageable data center solution for hospitals.Meth-ods Through comparative analysis and empirical research,this study explores how hyper-converged technology can help hospitals optimize resource allocation,improve service quality,and ensure data security.Results Hyper-converged technology demon-strates significant benefits in assisting hospitals to optimize resource allocation,enhance service quality,and guarantee data secur-ity.Conclusion Hyper-converged technology offers distinct advantages in terms of cost,operation and maintenance,and relia-bility,making it a mainstream trend in future hospital data center construction.

A quadruplex RT-qPCR method was developed for rapid identification and diagnosis of transmissible gastroenteritis virus(TGEV)of swine,porcine epidemic diarrhea virus(PEDV),porcine deltacorona virus(PDCoV),and porcine rotavirus type A(PoRVA).The full-length sequences of PEDV(77 strains),TGEV(63 strains),PDCoV(17 strains)that are prevalent in China,as well as the 85 VP6 gene sequences of PoRVA,were downloaded from the NCBI database for homology analysis.Based on the relatively conserved sequences,the corresponding primers and probes for each virus were designed and used to establish the quadruplex RT-qPCR method.After optimization of the probes and the reaction conditions,the specificity,sensitivity,and repeatability were determined.Using the established method,109 clinical samples of diarrhea were tested and further compared with the results by standard method.The results showed that the quadruplex RT-qPCR method established in this experiment has good amplification effect,with the C,value linearly correlated with the copies of templates(R2＞0.99).Specificity assay demonstrated that the quadruplex RT-qPCR method can identify TGEV,PEDV,PDCoV,PRoVA strains,and do not de-tect African swine fever virus(ASFV),porcine circovirus type 2(PCV2),porcine reproductive and respiratory syndrome virus(PRRSV),classical swine fever virus(CSFV),pseudorabies virus(PRV)and other epidemic viruses.Sensitivity assay showed that the detection limits for TGEV,PEDV,PDCoV and PoRVA were 10,20,20 and 50 copies/μL,respectively.The method exhibits excellent reproducibility,with coefficients of variation(Cv)for both intra-and inter-assay repli-cates being less than 1％.Detection of 109 samples of diarrhea by this method yielded the coinci-dence rate of 100％with the industry standard,indicating high practical applicability.The devel-oped method possesses the advantages of strong strain compatibility,high sensitivity,strong speci-ficity,good repeatability and stability.It is suitable for virus diagnosis and large-scale clinical sam-ple testing,providing technical support for disease prevention and control as well as epidemiologi-cal investigation.

Objective This study sought to accelerate the establishment of a Parkinson's disease mouse model by intracerebral injection of α-synuclein preformed fibrils(α-Syn PFF)into B6-hSNCA-A53T transgenic mice to induce rapid development of Parkinson's-like pathological features.Methods C57BL/6J background α-Syn A53T transgenic mice were selected as the model group,with isogenic C57BL/6J mice as the control group.α-Syn PFF was delivered into the bilateral striatum using stereotactic brain injection.After modeling,the open-field test was used to assess spontaneous activity and anxiety-like behaviors,while the rotarod,grip strength,and pole tests evaluated motor coordination and limb muscle tone.The buried food test was conducted to assess olfactory function.Immunohistochemical staining was performed to investigate neuroinflammation and pathological α-synuclein in the mouse brain.Results Compared with the control group,1 month after the α-Syn PFF injection,model mice showed increased locomotion in the open-field test,with no significant differences in the rotarod,grip strength,or pole tests,but prolonged food-seeking time.Two months after model establishment,the model group showed significantly reduced locomotor activity in open field testing,impaired motor coordination in rotarod,grip strength and pole tests,and olfactory dysfunction in buried food tests.Phosphorylated α-synuclein accumulation was observed in the substantia nigra,cortex,and hippocampus,accompanied by pronounced microglial activation,Lewy body deposition,and substantial dopaminergic neuron loss in the substantia nigra.Conclusions A53T mice developed olfactory dysfunction and motor impairments more rapidly after α-Syn PFF injection.Significant pathological changes were observed,including the aggregation of α-synuclein/Lewy body in the substantia nigra,cortex,and hippocampus,and the loss of dopaminergic neurons in the substantia nigra.This model can serve as a rapidly established animal model for α-synucleinopathy-related Parkinson's disease.

Objective This study sought to accelerate the establishment of a Parkinson's disease mouse model by intracerebral injection of α-synuclein preformed fibrils(α-Syn PFF)into B6-hSNCA-A53T transgenic mice to induce rapid development of Parkinson's-like pathological features.Methods C57BL/6J background α-Syn A53T transgenic mice were selected as the model group,with isogenic C57BL/6J mice as the control group.α-Syn PFF was delivered into the bilateral striatum using stereotactic brain injection.After modeling,the open-field test was used to assess spontaneous activity and anxiety-like behaviors,while the rotarod,grip strength,and pole tests evaluated motor coordination and limb muscle tone.The buried food test was conducted to assess olfactory function.Immunohistochemical staining was performed to investigate neuroinflammation and pathological α-synuclein in the mouse brain.Results Compared with the control group,1 month after the α-Syn PFF injection,model mice showed increased locomotion in the open-field test,with no significant differences in the rotarod,grip strength,or pole tests,but prolonged food-seeking time.Two months after model establishment,the model group showed significantly reduced locomotor activity in open field testing,impaired motor coordination in rotarod,grip strength and pole tests,and olfactory dysfunction in buried food tests.Phosphorylated α-synuclein accumulation was observed in the substantia nigra,cortex,and hippocampus,accompanied by pronounced microglial activation,Lewy body deposition,and substantial dopaminergic neuron loss in the substantia nigra.Conclusions A53T mice developed olfactory dysfunction and motor impairments more rapidly after α-Syn PFF injection.Significant pathological changes were observed,including the aggregation of α-synuclein/Lewy body in the substantia nigra,cortex,and hippocampus,and the loss of dopaminergic neurons in the substantia nigra.This model can serve as a rapidly established animal model for α-synucleinopathy-related Parkinson's disease.

Objective:To investigate the prevalence and risk factors of overweight and obesity among Chinese children aged 3-18 years from 11 provinces, antonomous regions, or municipalities.Methods:This national cross-sectional community health survey utilized a multistage stratified cluster-random sampling method to recruit 193 997 nationally representative participants from 11 provinces, autonomous regions, or municipalities between January 2017 and December 2019. All participants underwent physical examinations, and their caregivers completed questionnaires assessing participants′ dietary, lifestyle, familial, and perinatal information. Multilevel multinomial logistic regression models were employed to identify the potential risk factors.Results:The cohort comprised 193 997 children (102 178 boys, 91 819 girls),aged (10±4) years. Overall prevalence rates were 30 574(15.8%)overweight children and 17 217(8.9%) obesity children. Boys exhibited higher overweight and obesity rates than girls (17.0% (17 368/102 178) vs. 14.4% (13 206/102 178), 11.3% (11 553/91 819) vs. 6.2% (5 664/91 819), χ2=249.12,1 578.69,both P<0.001). The detection rates of obesity in Tanner stage 2 and 3 were the highest in boys and girls, with 13.4%(2 231/16 665) and 8.6%(880/10 221) respectively. Risk factors for obesity included parental overweight (paternal OR=2.34 and maternal OR=2.29), annual household income of 100 000-200 000 yuan (compared with<100 000 yuan, OR=1.04), higher paternal education (compared with below high school,high school and a college education OR=1.09,1.14), birth weight >4.0 kg (≤5 and>5 years old OR=1.74, 1.44,respectively), and western food consumption≥1 time/month (compared with<1, 1-2, 3-4,>4 times/month OR=1.36, 1.30, 1.67(≤5 years), 1.19, 1.16, 1.15 (>5 years), respectively) (all P<0.05). Conversely, coarse grain intake≥1 times/week (compared with<1 times/week, every day, 3-4, 1-2 times/week OR=0.74, 0.80, 0.71 (≤5 years), 0.75, 0.87, 0.90(>5 years), respectively, all P<0.05) was associated with reduced obesity risk. Conclusions:Obesity epidemiology in children demonstrates significant heterogeneity across age, gender, geographic regions, and pubertal stages. It is necessary to establish a personalized prevention and control strategy.

Objective To provide an efficient,reliable,and easily manageable data center solution for hospitals.Meth-ods Through comparative analysis and empirical research,this study explores how hyper-converged technology can help hospitals optimize resource allocation,improve service quality,and ensure data security.Results Hyper-converged technology demon-strates significant benefits in assisting hospitals to optimize resource allocation,enhance service quality,and guarantee data secur-ity.Conclusion Hyper-converged technology offers distinct advantages in terms of cost,operation and maintenance,and relia-bility,making it a mainstream trend in future hospital data center construction.