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.

Objective: To explore the association between the HLA antibody positivity rate in female blood donors and pregnancy history, number of pregnancies, interval from the last pregnancy to blood donation, and age, to identify associated variables using a univariate generalized additive model (GAM), and to further analyze the predictive role of characteristic variables for HLA antibody positivity using a random forest model. Methods: HLA antibody detection was performed on 391 female blood donors using the Luminex immunomagnetic bead method. The correlation between pregnancy-related factors and HLA antibodies was analyzed using the Chi-square test. Based on R software, a univariate GAM was first constructed to analyze the association types between characteristic variables and the HLA antibody positivity rate, followed by the construction of a random forest model to evaluate the predictive value of the variables. Results: Among the 391 female blood donors without a transfusion history, the overall HLA antibody positivity rate was 26.34%. The positivity rate in donors with a pregnancy history was significantly higher than that in those without (30.09% vs 9.72%, P<0.05), and HLA antibody positivity rate increased linearly with the number of pregnancies (P<0.05). In the univariate GAM, age and number of deliveries exhibited a non-linear association with the HLA antibody positivity rate (the positivity rate increased sharply between 25-35 years of age and stabilized after 3 deliveries). Besides, the interval from the last pregnancy to blood donation showed a linear association with the HLA antibody positivity rate, and the positivity rate decreased as the interval prolonged (P<0.05). In the random forest model, age (mean decrease gini=29.26) and interval from the last pregnancy to blood donation (mean decrease gini=22.02) were core predictive variables: age was more conducive to identifying positive samples, while the interval from the last pregnancy to blood donation was more helpful for excluding negative samples. The number of deliveries (mean decrease accuracy=16.98) made a significant contribution to predicting positive samples, whereas the number of abortions had no impact. The model had an AUC of 0.583 (95% CI: 0.593 8-0.770 2), indicating a certain predictive value. Conclusion: The associated variables identified by the univariate GAM model, including age, interval from the last pregnancy to blood donation, and number of deliveries, provide a basis for key variables in the random forest model. All three variables have predictive value for HLA antibody positivity, which can provide evidence-based support for personalized transfusion management and stratified screening of female blood donors in this region.

Background Microparticles (MPs) are one of the main medium of inflammatory reaction with an important role in atherosclerotic progression. Studies on association of air pollution exposure and levels of peripheral blood MPs are limited among human. Objective To evaluate the effects of short-term exposure to air pollution on levels of peripheral blood MPs. Method A panel of 73 healthy adults was followed with 4 repeated follow-ups in Beijing, China, from November 2014 to January 2016. During each visit, we collected questionnaire information, fasting venous blood, urine, and exposures to fine particulate matter (PM_2.5), black carbon, nitric oxide, nitrogen dioxide, nitrogen oxide, sulfur dioxide, carbon monoxide, and ozone. We used linear mixed-effect models to analyze associations of air pollution exposure with levels of total MPs (TMPs) and MPs derived from various cells. Stratified analysis was conducted by levels of C-reactive protein (CRP) and malondialdehyde (MDA). Results The results showed significant associations between air pollution exposure and peripheral blood TMPs at 2 h-6 d prior to the follow-ups (P<0.05), while no statistical associations were found for MPs derived from different cell types. Significant increases in TMPs of 7.8% (95%CI: 0.7%, 15.3%) and 14.3% (95%CI: 2.8%, 27.2%) were observed with each interquartile range (IQR) increase in PM_2.5 (IQR=64.9 μg·m⁻³) at prior 18 h and NO (IQR=40.5 μg·m⁻³) at prior 48 h. Among participants with low levels of CRP and MDA, significantly positive associations were observed between air pollution exposure and levels of TMPs (P<0.05). Conclusion Short-term exposure to air pollution is significantly associated with increased levels of circulating MPs in healthy adults, and in people with lower systemic inflammation, peripheral blood MPs levels are more easily affected after exposure to air pollutants.

Objective To investigate the epidemiological characteristics of malaria and provide a basis for developing improved prevention and control measures. Methods Data were obtained from the Chinese Disease Prevention and Control Information System. Malaria surveillance data for Nanning City from January 1,2023, to December 31,2024, were exported from the Infectious Disease Reporting Information Management Subsystem. The characteristics of the two groups of malaria cases were compared. Results A total of 103 imported malaria cases were reported in Nanning City in 2024, representing a 38.32% decrease compared with the same period of the previous year. No statistically significant difference were observed between cases reported in 2023 and 2024 in terms of average age, gender ratio, proportion of parasite species, and monthly reporting distribution;however, statistically significant differences were found in the proportion of reporting areas and current residence areas(χ2= 13.572 and 10.355, respectively; P = 0.001 and 0.035, respectively). The proportion of cases reported in Shanglin County and the proportion of cases residing in Shanglin County were both lower than those during the same period of the previous year. Conclusions The high aggregation of imported malaria cases in Nanning City has decreased. Medical institutions in areas other than Shanglin County should strengthen their vigilance against malaria.

ObjectiveTo investigate the protective effect of liver-targeted fibroblast growth factor 21 （FGF21） overexpression against CCl₄-induced acute liver injury （ALI） and its association with silent information regulator 1/glutathione peroxidase 4 （SIRT1/GPX4） expression and ferroptosis-related markers. MethodsFemale ICR mice （8 weeks old） were randomly divided into Control， CCl₄， adeno-associated virus （AAV）-FGF21， and AAV-FGF21 + CCl₄ groups. Liver-targeted FGF21 overexpression was achieved via tail vein injection of AAV8-FGF21 virus with green fluorescent protein （GFP） labeling. ALI was induced by intraperitoneal injection of CCl₄ （0.3 mL/kg）， with sample collection at 12 hours. Body weight and liver weight were recorded to calculate the liver weight/body weight. Alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using a biochemical analyzer. FGF21 expression in liver tissues was detected by immunofluorescence. Hepatic histopathology was evaluated by HE staining. RT-qPCR was performed to assess mRNA expression of ferroptosis and iron metabolism-related genes （ACSL4， PTGS2， HJV， FPN， GPX4）， FGF21， and SIRT1. Protein expression of FGF21， SIRT1， and GPX4 were determined by Western blot. Iron content， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） activity in liver homogenate were quantified using assay kits. ResultsCompared with the Control group， the FGF21 mRNA and protein expression elevated in CCl₄ group； serum ALT/AST levels and liver weight/body weigh increased. The HE staining results showed that the liver cell membranes were ruptured. The mRNA levels of ACSL4 and PTGS2， the iron content and MDA levels all increased （P<0.01）. The mRNA levels of SIRT1， GPX4， HJV， and FPN， the GSH level and SOD activity all decreased （P<0.05）， and the protein levels of SIRT1 and GPX4 both decreased （P<0.05）. Compared with the CCl₄ group， the serum levels of ALT and AST in the AAV-FGF21 + CCl4 group were decreased （P<0.01）， and the liver/body ratio of mice decreased （P<0.01）. The results of HE staining showed that the degree of liver injury was alleviated. The mRNA levels of ACSL4 and PTGS2， iron content and MDA level all decreased （P<0.01）， while the mRNA levels of SIRT1， GPX4， HJV， FPN， GSH level and SOD activity all increased （P<0.05）. The protein levels of SIRT1 and GPX4 both increased （P<0.05）. ConclusionFGF21 overexpression is associated with enhanced SIRT1/GPX4 expression and suppression of ferroptosis features， thereby contributing to the alleviation of CCl₄-induced ALI.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

To investigate the therapeutic effect and related mechanisms of hordenine on ovalbumin (OVA)-induced allergic rhinitis (AR) in rats, HE and AB-PAS staining were used to detect the improvement of pathological damage to the nasal mucosa induced by hordenine. ELISA was employed to detect the effect of hordenine on OVA-sIgE in serum and IL-4 in the nasal mucosa supernatant of rats. IHC and Western blot experiments were undertaken to examine the effect of hordenine on Th1/Th2 cell balance. Bioinformatics analysis was performed to predict pathways, which were verified by in vivo and in vitro experiments. The experimental results showed that hordenine could alleviate the behavioral manifestations of OVA-induced AR rats, alleviate nasal mucosal pathological damage caused by AR, and reduce the secretion of OVA-sIgE and IL-4. In addition, hordenine could regulate the Th1/Th2 balance. Bioinformatics analysis results showed that the potential pathway of action of hordenine on AR was the phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. The in vivo experimental results showed that the expression of PI3K and p-Akt proteins in the nasal mucosa of the model group rats was significantly increased (P < 0.01), and that the protein expression level was significantly decreased after the administration of hordenine, which was also confirmed by an in vitro experiment. This study suggests that hordenine may regulate Th1/Th2 cell balance through the PI3K/Akt signaling pathway, thereby exerting an alleviating effect on OVA-induced AR.

OBJECTIVE To explore the mechanism of Shenqi guben formula （SQGB） in improving cancer-related fatigue （CRF） based on network pharmacology and cellular experiments. METHODS Active components of SQGB and CRF-related targets were identified on the basis of databases such as the Traditional Chinese Medicine Systems Pharmacology platform. An in vitro CRF cell model was established by inducing A549 cells with interleukin-17 （IL-17）. Cells were treated with low （1.0 mg/mL） or high （1.5 mg/mL） concentrations of SQGB. The effects on cell viability， migration， apoptosis， inflammatory factors， mRNA expression， apoptosis-related proteins and key proteins 011） of IL-17 signaling pathway were evaluated using scratch assay， flow cytometry， ELISA， real-time fluorescent quantitative PCR and Western blot analysis. RESULTS SQGB contained 84 active components acting on 209 potential CRF targets. Among E-these， quercetin， kaempferol， and luteolin were identified as the core components of the compound. Core targets included tumor protein p53， AKT serine/threonine kinase 1， IL-6， and tumor necrosis factor （TNF）. IL-17， TNF and phosphatidylinositol-3- kinase-serine/threonine protein kinase （PI3K/Akt） signaling pathways were identified as crucial pathways. Compared with IL-17 intervention group， the cell migration rate， B-cell lymphoma 2 （Bcl-2） protein expression， the levels of IL-6 and TNF-α in the supernatant， mRNA expression of IL-17 receptor A （IL-17RA）， TNF-α， and IL-6， as well as the protein expression of IL-17RA and nuclear factor kappa-B p65 subunit （p65）， and phosphorylated （p）-p65/p65 ratio in IL-17+SQGB low- and high- quality concentration groups were all significantly decreased or down-regulation （P＜0.05）； the apoptosis rate， expression levels of Bcl-2 associated X protein （Bax） and cleaved caspase-3 protein， the ratio of Bax/Bcl-2， the expression level of p-p38 protein， and the p- p38/p38 ratio were all significantly increased or up-regulated （P＜0.05）. Moreover， the improvement effects of these indicators were mostly better in the high-quality concentration groups compared to the low-quality concentration groups （P＜0.05）. CONCLUSIONS SQGB ameliorates CRF by regulating the IL-17 signaling pathway， inhibiting the expression of inflammatory factors， and activating p38 MAPK-dependent apoptosis pathway.

ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China