1.TGF-β1-engineered Biomimetic Platelet Nanoparticles for Targeted Therapy of Ischemic Stroke
Li-Qi CHEN ; Tian-Fang KANG ; Guo-Jun HUANG ; Ting YIN ; Ai-Qing MA ; Lin-Tao CAI ; Hong PAN
Progress in Biochemistry and Biophysics 2026;53(3):697-710
ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.
2.Analysis of biotypes and genetic diversity of five non-major pathogenic Brucella species
Miao WANG ; Ying-qi WANG ; Chun-fang LIU ; Song-nan DU ; Zhi-guo LIU ; Zhen-jun LI
Chinese Journal of Zoonoses 2025;41(2):136-141
This study was aimed at analyzing the biotypes and genetic diversity characteristics of five non-major Brucella species,to provide a scientific basis for understanding the species diversity of Brucella and strengthening pathogen monitoring and control.According to the biotypes(species,hosts,isolation locations,and time)and MLVA-16 genotypes(MLVA-16 lo-cus data,MLVA-11 genotypes)of five non-major pathogenic Brucella in the international MLVA database,we used Bionu-merics 8.0 software and PHYLOVIZ2.0 online software to analyze the geographical origin and genetic diversity characteristics of strains.A total of 227 strains were studied,including 121 Brucella ceti,47 B.pinnipedialis,37 Brucella ovis,11 B.mi-croti,and Brucella neotomae.The greatest host diversity was observed for B.ceti,followed by B.pinnipedialis and B.mi-croti.B.ceti was distributed in European and South American countries;B.pinnipedialiswas distributed in Europe;and B.microti.was distributed in the Czech Republic,Austria,and Hungary in Central Europe.B.ovis was widely distributed in Af-rica,Argentina,Australia,Brazil,Greece,the United States,Spain,and France.The MLVA-11 genotypes of different types of Brucella showed high polymorphism and large differences,thus suggesting that the strains have different geographical ori-gins.MST analysis indicated that the studied strains were divided into four branches(BCⅠ-Ⅳ),among which B.ceti was di-vided into two different branches(BC-Ⅰ and BC-Ⅱ),the strains of other types formed different branches(or sub-branches),and the strains of different types showed clear regional and dominant host characteristics.Genetic correlation analysis of strains of the Brucella genus revealed that non-major pathogenic Brucella had clear genetic,distribution,and host spectrum differ-ences with respect to four classical pathogenic Brucella species.Five non-major pathogenic Brucella strains presented unique genetic evolutionary patterns,geographical distributions,and host tropism characteristics,thereby providing new insight for understanding the biological and genetic diversity of those Brucella strains.
3.Study on Risk Factors and Etiology of Urinary Tract Infection Caused by Urinary Calculi in Eastern Fujian Region
Jian CHEN ; Jian-ping WU ; Jian-jun LI ; Guo-min LI ; Fei-hui FANG ; Qiao-ming LIN
Progress in Modern Biomedicine 2025;25(9):1534-1541
Objective:To explore the risk factors and etiological characteristics of urinary tract infection caused by urinary calculi in eastern Fujian region,in order to attract clinical attention and improve the prevention and treatment of urinary tract infection caused by urinary calculi.Methods:A total of 154 patients with urinary calculi admitted to Ningde People's Hospital(n=80)and Ningde Mindong Hospital(n=74)from November 2022 to October 2023 were selected as the main research objects.According to whether the patients had urinary tract infection,they were divided into infection group and non-infection group.The baseline data of the two groups were analyzed in detail,and the risk factors and pathogen distribution of urinary tract infection in patients with urinary calculi were analyzed.Results:There were 33 cases of urinary tract infection in 154 patients with urinary calculi,accounting for 21.43%.Univariate analysis showed that the urinary white blood cell count in the infection group was higher than that in the non-infection group,and the proportion of patients with effusion,urinary tract obstruction,calculi in the upper urinary tract,staghorn calculi,smoking history,diabetes,and urinary nitrite positive was higher than that in the uninfected group(P<0.05).The results of binary logistic regression analysis showed that effusion,urinary tract obstruction,staghorn calculi,smoking history,diabetes,high urine white blood cell count and positive urine nitrite were independent risk factors for urinary tract infection in patients with urinary calculi(OR>1,P<0.05).A total of 33 strains of pathogenic bacteria were isolated from 33 patients in the infection group.Among them,23 strains(69.70%)were gram-negative bacteria,8 strains(24.24%)were gram-positive bacteria,and 2 strains(6.06%)were fungi.Among gram-negative bacteria,escherichia coli accounted for the highest proportion(48.48%),followed by klebsiella pneumoniae(9.09%).Among gram-positive bacteria,enterococcus faecalis accounted for the highest proportion(12.12%),followed by enterococcus faecium(6.06%).Candida and candida tropicalis in fungi was the same,accounted for 3.03%.Conclusion:The risk of urinary tract infection in patients with urinary calculi in eastern Fujian region is high.Effusion,urinary tract obstruction,staghorn calculi,smoking history,diabetes,high urine white blood cell count and positive urine nitrite are independent risk factors for urinary tract infection in patients with urinary calculi.The main urinary tract pathogens are gram-negative bacteria.
4.Diaphragm ultrasound can predict extubation outcomes for brain-injured patients
Guosheng WANG ; Lei ZHAO ; Chenxia GUAN ; Zhe LI ; Jun GUO ; Mingzhu FANG ; Yingzi LIANG
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(3):249-254
Objective:To evaluate the effectiveness of diaphragm ultrasound in predicting the success of extubation from tracheotomy in patients with acquired brain injury.Methods:A retrospective analysis was conducted on 51 brain-injured patients. They were divided into an extubation failure group and an extubation success group. The results of ultrasound examination of the diaphragm in the 2 groups were analyzed by univariate analysis, and the independent variables with significance were further subjected to multivariate logistic regression analysis. R software was applied to build the diaphragm indicators showing significant predictive power into a histogram model. The predictive value of this nomogram model was assessed using the receiver operating characteristics (ROC) curve.Results:The univariate analysis revealed significant differences between the two groups in terms of diaphragm excursion, diaphragm thickening fraction and diaphragm excursion-time index. The multivariate logistic regression analysis and the nomogram showed that those three variables are independent influencing factors predicting the success of decannulation. The areas under the ROC curves confirmed that finding.Conclusions:Diaphragm excursion, diaphragm thickening fraction and the diaphragm excursion-time index are useful independent predictors of the success of decannulation among brain injury patients.
5.Effects of high-fat diet intake on pharmacokinetics of rabeprazole sodium enteric-coated tablets in healthy Chinese subjects
Cai-hui GUO ; Yu-fang XU ; Cong-yang DING ; Guang-tao HAO ; Hao-jing SONG ; Xue SUN ; Zhan-jun DONG ; Wan-jun BAI
The Chinese Journal of Clinical Pharmacology 2025;41(2):225-229
Objective To evaluate the effects of fasting and high-fat diet on the pharmacokinetics of rabeprazole sodium enteric-coated tablets in healthy Chinese subjects.Methods A single-center,randomized,open,two-agent,two-sequence,four-cycle,fully repeated crossover,single-dose trial design was used in this study,healthy subjects were assigned to receive single dose of rabeprazole sodium enteric-coated tablets 0.1 g in either fasting or high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of rabeprazole sodium enteric-coated in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),the model method of the non-compartmental was used to calculate the pharmacokinetic parameters by Phoenix WinNonlin 8.2.Results The main pharmacokinetic parameters of rabeprazole sodium enteric-coated tablets in fasting state and high-fat diet state were as follows:Cmax were(339.63±156.47)and(318.86±132.13)ng·mL-1;t1/2 were(2.34±0.68)and(3.60±2.40)h;AUC0_t were(556.62±251.65)and(528.50±201.78)ng·mL-1·h;AUC0-∞ were(563.39±255.69)and(535.15±203.24)ng·mL-1·h;tmax were 3.65 and 6.99 h.After high-fat diet,the Cmax and AUC of rapeprazole sodium after high-fat and high-calorie diet decreased,Cmax decreased by 6.12%,AUC0-t decreased by 5.05%,AUC0-∞ decreased by 5.01%,andtmaxwas delayed by about 3.34 h.Cmax,AUC0-t and AUC0-∞ 90%confidence interval were 73.13%-115.10%,83.22%-112.28%and 83.40%-112.13%,respectively.Neither was between 85.00%-125.00%.Conclusion High-fat diet affects the absorption rate and degree of rabeprazole sodium enteric-coated,so it is suitable to be administered on an empty stomach.
6.Establishment of a LC-MS/MS method for detecting gamma-aminobutyric acid in plasma and its clinical application
Jia-qian QIN ; Lei CAO ; Ying-fei PENG ; Fang-jun CHEN ; Bai-shen PAN ; Bei-li WANG ; Wei GUO
Fudan University Journal of Medical Sciences 2025;52(5):708-716
Objective To establish a stable liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for detecting gamma-aminobutyric acid(GABA)in plasma,and to evaluate the value of GABA detection in the diagnosis of sleep disorders.Methods GABA was detected using a UPLC Xevo TQs system.The method was pre-validated and its performance was verified to establish a reference range for healthy individuals.The difference in plasma GABA levels between apparently healthy individuals and patients with sleep disorders was compared.Results We employed deuterated compounds as isotopic internal standards and utilized an Amide chromatographic column for separation.The mobile phase was 0.050%formic acid in water and 90%acetonitrile in water containing 0.175%formic acid and 5 mmol/L ammonium acetate with gradient elution in the column temperature of 35℃.The linear range for the detection of GABA by LC-MS/MS was 0.05-10.00 μmol/L,with a lower limit of quantification of 0.02 μmol/L,the inter-day CV<3.00%and intra assay CV<4.00%,respectively,and the recovery rate was 101.06%-109.02%.The reference ranges for plasma GABA were established by analyzing 300 healthy controls stratified by age:18-34 years(0.08-0.15 μmol/L),35-49 years(0.10-0.20 μmol/L),and≥50 years(0.12-0.23 μmol/L).Then plasma GABA was used as a biomarker for auxiliary diagnosis of sleep disorders in analyzing 221 patients and 300 healthy controls,which revealed that AUC values were 0.510(P=0.850),0.686(P=0.002),and 0.890(P<0.001)in the groups of 18-34 years,35-49 years,and≥50 years,respectively,with optimal cut-off values of 0.09,0.10 and 0.11 μmol/L.Conclusion A reliable LC-MS/MS method for detecting GABA has been established,which can detect plasma GABA levels sensitively and accurately and can be used in assisting the clinical diagnosis of sleep disorders.
7.Treatment and mechanism of chrysoeriol on pulmonary hypertension based on network pharmacology and experimental study
Ying-fang MA ; Meng CAI ; Dan FENG ; Yang GUO ; Yu-he TIAN ; Yun-hua ZHANG ; Li-li WEI ; Yang WANG ; Jun-qiang SI
Chinese Pharmacological Bulletin 2025;41(11):2167-2176
Aim To investigate the effect of chrysoeriol on pulmonary vascular remodeling in pulmonary hyper-tension by animal experiments combined with cell ex-periments,and to explore its potential therapeutic tar-gets by network pharmacology.Methods The target of chrysoeriol was collected in Targetnet,SEA and SwissTargetPrediction database.Pulmonary arterial hy-pertension(PAH)targets were collected in the Dis-GeNET and GeneCards databases,and PPI network map was drawn in the STRING database,and key tar-gets were screened.The GO and KEGG pathway en-richment analysis was carried out through DAVID data-base and Weishengxing platform.AutoDock software was used for molecular docking of key core targets.The PAH model of rats was constructed,and the pulmo-nary hemodynamics and vascular remodeling were de-tected by echocardiography,HE and Masson staining.Primary pulmonary smooth muscle cells were extracted,and the effects of drugs on pathway proteins were de-tected in vitro.Results The results of network phar-macology showed that chrysoeriol exerted therapeutic effects on pulmonary hypertension by affecting key tar-gets such as AKT1,SRC,EGFR,MMP9 and gsk3 β,and signaling pathways such as EGFR and PI3K-AKT.Molecular docking showed that chrysoeriol had good binding ability with 5 key target genes.Animal experi-ments showed that the pulmonary hemodynamic func-tion of PAH rats was significantly improved after ad-ministration of chrysoeriol.The remodeling of small pulmonary arteries was significantly reduced.Cell ex-periments showed that chrysoeriol could inhibit the ex-pression of proliferation,migration and phenotypic transformation genes.Conclusion Chrysoeriol may play a role in the treatment of pulmonary hypertension through multiple targets.
8.Radiation hardening study for control chips in casualty transport robots
Jian-jun CHEN ; Fang GUO ; Zhen-dong ZHENG
Chinese Medical Equipment Journal 2025;46(11):18-23
Objective To explore the performance of gallium nitride(GaN)-based digital circuit chips applied in nuclear radiation environments and investigate the feasibility of their use in control chips for robots transporting injured personnel.Methods First,a GaN-based NAND gate digital circuit chip was fabricated.Second,both the GaN-based digital chip and the SN74AHCT1G00 silicon-based digital chip were irradiated with 60Co gamma-ray.The irradiation doses for the GaN-based digital chip were 1 Mrad(Si)and 2 Mrad(Si),while the irradiation dose for the SN74AHCT1G00 silicon-based digital chip was 1 Mrad(Si).Finally,the post-irradiation electrical performance of the two chips was measured using a Keithley 4200A-SCS semiconductor characterization system.Results Under 60Co gamma-ray irradiation doses of 1 Mrad(Si)and 2 Mrad(Si),the response delay of the GaN-based digital circuit chip was only on the order of 0.1 μs.In contrast,the response rate of the SN74AHCT1G00 silicon-based digital circuit chip significantly degraded under 60Co gamma-ray irradiation dose of 1 Mrad(Si),rendering it unable to perform the NAND gate logic function.Conclusion GaN-based digital circuit chips exhibit high radiation resistance in 60Co gamma-ray irradiation environments,with no significant performance degradation.Compared with silicon-based digital circuit chips,they demonstrate considerable advantages and can preliminarily meet the requirements for control chips of robots transporting injured personnel in nuclear radiation environments.
9.Metabolomic analysis of Agrimonia pilosa intervention in proliferation and apoptosis of H1299 cells based on UHPLC-Q-Orbitrap MS technology
Ze-hua TONG ; Wen-jun GUO ; Meng LI ; Ya-juan XU ; Hong-ming ZHANG ; Ze-yu DOU ; Sheng-xu XIE ; Wei-fang WANG
Chinese Pharmacological Bulletin 2025;41(5):970-978
Aim To investigate the effects of Agrimonia pilosa(AP)on the proliferation and apoptosis of non-small cell lung cancer(NSCLC)H1299 cells using non-targeted metabolomics and other methods,and to explore the underlying molecular mechanisms.Meth-ods Taking H1299 cells as the research object,the effect of AP on cell proliferation and apoptosis was de-tected through CCK-8 method,colony formation,LDH,Hoechst 33258 staining,AO/EB staining,flow cytometry detection,RT qPCR and other experiments.The main differential metabolites were detected by the metabolomics method of ultra-high phase liquid chro-matography and mass spectrometry(UHPLC-Q-Orbi-trap MS),and related metabolic pathways were ana-lyzed.Results Compared with the control group,AP treatment was able to significantly inhibit the prolifera-tion and colony formation of H1299 cells,while the re-lease of LDH increased in a dose-dependent manner.Fluorescence microscopy and flow cytometry and RT-qPCR analysis revealed that H1299 cells underwent crumpling and increased nuclear fragmentation after AP administration,blocked in G0/G1 phase,up-regulated apoptotic genes caspase-3 and Bax,and down-regulated apoptosis-inducing effects of Bcl-2.Metabolomics anal-ysis screened 35 differential metabolites,which were PC(O-30∶1),D-Glutamic acid,PE(18∶0/15∶0),etc.The main metabolic pathways involved includ-ed amino acid metabolism,glycerophospholipid metabo-lism and purine metabolism so on.Conclusions AP may exert its pharmacological effects by interfering with multiple metabolic pathways in H1299 cells,inhibiting cell proliferation and promoting apoptosis.
10.Diaphragm ultrasound can predict extubation outcomes for brain-injured patients
Guosheng WANG ; Lei ZHAO ; Chenxia GUAN ; Zhe LI ; Jun GUO ; Mingzhu FANG ; Yingzi LIANG
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(3):249-254
Objective:To evaluate the effectiveness of diaphragm ultrasound in predicting the success of extubation from tracheotomy in patients with acquired brain injury.Methods:A retrospective analysis was conducted on 51 brain-injured patients. They were divided into an extubation failure group and an extubation success group. The results of ultrasound examination of the diaphragm in the 2 groups were analyzed by univariate analysis, and the independent variables with significance were further subjected to multivariate logistic regression analysis. R software was applied to build the diaphragm indicators showing significant predictive power into a histogram model. The predictive value of this nomogram model was assessed using the receiver operating characteristics (ROC) curve.Results:The univariate analysis revealed significant differences between the two groups in terms of diaphragm excursion, diaphragm thickening fraction and diaphragm excursion-time index. The multivariate logistic regression analysis and the nomogram showed that those three variables are independent influencing factors predicting the success of decannulation. The areas under the ROC curves confirmed that finding.Conclusions:Diaphragm excursion, diaphragm thickening fraction and the diaphragm excursion-time index are useful independent predictors of the success of decannulation among brain injury patients.

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