Objective To analyze the influencing factors of malaria infection of labor service exported to overseas in Langfang City, in order to establish a visualization tool to assist clinicians in predicting the risk of malaria. Methods A total of 4 774 expatriate employees of the Nibei Pipeline Project of the Pipeline Bureau from October 2021 to August 2023 were taken as the subjects, and the gender, age, overseas residence area and Knowledge of malaria controlscores of the study subjects were investigated by questionnaire survey, and the possible risk factors of malaria were screened by logistic regression model. At the same time, the nomogram prediction model was established, and the subjects were divided into the training group and the validation group at a ratio of 2:1, and the area under the curve (ROC) and the decision curve were plotted to evaluate the prediction ability and practicability of the prediction model in this study. Results Among the 4 774 study subjects, 96 cases of malaria occurred, and the detection rate was 2.01%. Junior school （OR=1.723，95% CI:1.361-2.173）， and residence in rural areas（OR=2.091，95%CI:1.760 -3.100）were risk factors (OR>1), while protective measures（OR=0.826，95% CI : 0.781 - 0.901） and high malaria education scores （OR=0.872，95% CI : 0.621 - 0.899）were protective factors.The nomogram prediction model results showed that the area under the curve of the nomogram prediction model in the training group was 0.94 (95% CI : 0.85 - 1.00), while the validation group was 0.93 (95% CI : 0.80 - 1.00). The results of the decision curve showed that when the threshold probability of the population was 0-0.9, the nomogram model was used to predict the risk of malaria occurrence with the highest net income. Conclusion The nomogram prediction model (including gender, education, region, protection and malaria education score) established and validated in this study is of great value for clinicians to screen high-risk patients with malaria.

In hypoxic-ischemic brain damage (HIBD), the programmed cell death known as ferroptosis is significantly activated. Microglial cells demonstrate a high level of sensitivity to iron accumulation. Understanding how to regulate the dual role of microglia and transforming the microglial ferroptosis to a moderate and controllable process has considerable implications for the targeted treatment in HIBD. This paper serves as an overview of microglia-mediated ferroptosis in HIBD as a disease model. We discuss various aspects centered around microglia, including pathophysiological mechanisms, polarization and functions of microglia, molecular mechanisms of ferroptosis, signaling pathways, and therapeutic strategies. The review aims to provide a reference for studies of ferroptosis in microglia.
Microglia/physiology* ; Ferroptosis/physiology* ; Humans ; Animals ; Hypoxia-Ischemia, Brain/pathology* ; Signal Transduction

The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

OBJECTIVES: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect. METHODS: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability. RESULTS: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential. CONCLUSIONS Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glucosides/pharmacology* ; Animals, Newborn ; Benzyl Alcohols/pharmacology* ; Amino Acid Transport System y+/metabolism*

Objective: To explore the intra class transmission pattern of acute hemorrhagic conjunctivitis (AHC) among students, so as to provide a basis for formulating precise prevention and control strategies. Methods: The data of AHC students in 2023 was obtained from the teacher-student health information module of the "Xiamen i-Education" platform. Taking the onset date from January 1st to December 31st, 2023 as the search criteria, the epidemiological data of confirmed AHC cases among students in the whole city in 2023 was collected. And the Knox test method was employed to quantify cluster risk at the class level. Subgroup comparisons were conducted to examine differences in cluster risk between academic stages and gender combinations. Cross analysis was performed to investigate the interactive effects of two characteristics on cluster risk. Results: In 2023, 708 cases of AHC students were reported in Xiamen, among which 54 class clustered outbreaks were identified. These outbreaks accounted for 40.54% of total cases. Among them, the incidence of class clustered outbreaks with male first onset cases was higher than that with female first onset cases ( χ 2=4.55, P <0.05). The class cluster risk was at a relatively high level within the incubation period (0-2 d) after AHC onset ( RR =4.61-6.43, P <0.05). Subgroup analysis revealed that female-female case pairs had a higher class cluster risk ( RR = 4.81- 10.29) compared to other gender combinations ( P <0.05). Primary school case pairs showed a higher risk ( RR =4.60-6.77) than middle school case pairs ( RR =3.85-4.57) (both P <0.05). Cross analysis indicated that primary school and female-female combinations had a higher risk ( RR =4.70-11.24) than other combinations, while middle school and male-female combinations showed a positive interaction ( RR =3.68-6.68)(both P <0.05). Conclusions AHC infection among students is primarily transmitted within classes. Gender and educational stage are key demographic factors influencing class cluster transmission risks. Transmission risks should be assessed by analyzing population characteristics and contact patterns, and targeted interventions should be implemented.

Objective To explore the probability and associated factors of pulmonary fibrosis in 350 cases of elderly pneumonia. Methods Elderly patients who received diagnosis and treatment at Changzhi Medical College Affiliated Peace Hospital from January 2018 to December 2022 were selected, and 350 patients who met the criteria were included in the study. Analyze its clinical data, incidence of pulmonary fibrosis, and analyze the relationship between the two. Results The average age of 350 patients was (63.51 ± 5.74) years old; 219 cases were common type , 72 cases were severe type, and 59 cases were critically ill. At admission, the CT signs were: ground glass in 66 cases (18.86%) , paving stone in 37 cases (10.57%), consolidation in 73 cases (20.86%), nodules in 93 cases (26.57%) , fried egg sign in 20 cases (5.71%) , and mosaic sign in 61 cases (17.43%). At discharge, the lesion signs were as follows: 61 cases (17.43%) had no lesions, 207 cases (59.14%) maintained the original lesion signs, and 82 cases (23.43%) evolved into other signs. 76 cases of pulmonary fibrosis were discharged, with an incidence rate of 21.71%. There were significant differences in the incidence of pulmonary fibrosis among patients with different ages, lesion evolution during treatment, lesion signs at discharge, and clinical stages (all P<0.001). Pulmonary fibrosis is positively correlated with age (P=0.047), lesion signs at discharge (P=0.032), and clinical classification (P=0.010). The incidence of lesions presenting as paving stones (P=0.014) and fibrosis in critically ill patients (P=0.013) at discharge is higher. Age increase (P=0.047) , wide range of lesions at admission (P=0.042), evolution of lesions into other signs at discharge (P=0.016), and clinical classification as severe (P=0.008) or critically ill (P=0.021) are independent risk factors for the development of pulmonary fibrosis in elderly pneumonia patients. Conclusion The incidence of pulmonary fibrosis in elderly patients exceeds 20%. Increasing age, wide range of lesions upon admission, evolution of lesions into other signs upon discharge, and clinical classification as severe or critically ill are independent risk factors for the occurrence of pulmonary fibrosis in elderly pneumonia patients.

AIM:To investigate the effect of gastrodin(GAS)on microglia-mediated inflammatory response after hypoxic-ischemic brain damage(HIBD)neonatal mice by regulating the expression of JAK1/STAT1 pathway through C-C chemokine recepeor 5(CCR5).METHODS:Forty-eight C57BL/6J mice at about 10 days after birth were randomly divided into sham group,HIBD model group and HIBD+GAS group.BV-2 microglia were divided into control(Con)group,oxygen glucose deprivation(OGD)group,oxygen glucose deprivation with gastrodin intervention(OGD+GAS)group,GAS group,Maraviroc(MVC)group,OGD+MVC group,and OGD+MVC+GAS group.The mRNA expression of CCL4 and CCR5 were detected by RT-qPCR.The protein expression of CCR5,p-JAK1,p-STAT1,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by Western blot.The expression of CCR5,p-JAK1 and p-STAT1 in cells were observed by immunofluorescence staining.RESULTS:(1)Compared with sham group,the expression levels of CCL4 and CCR5 mRNA,and CCR5,p-JAK1 and p-STAT1 proteins were significantly higher in the ischemic side of the corpus callosum in HIBD group(P＜0.05).(2)Compared with Con group,the protein levels of CCR5,p-JAK1 and p-STAT1 significantly increased in BV-2 cells of OGD group(P＜0.05).The protein levels of CCR5,p-JAK1 and p-STAT1 in BV-2 cells of OGD+GAS group were significantly lower than those of OGD group(P＜0.05).(3)Maraviroc did not cause significant BV-2 cell death in the 0～80 μmol/L range.The p-JAK1 and p-STAT1 protein levels in MVC+OGD group were significantly lowered compared with OGD group(P＜0.05),but no significant difference was found between MVC+ OGD and OGD+MVC+GAS groups.CONCLUSION:Gastrodin can exert neuroprotective effects via CCR5/JAK1/STAT1 signaling pathway.

This study explores the potential antiepileptic mechanism of ursolic acid(UA)and its improvement of GABAergic interneuron damage induced by epilepsy based on transcriptome analysis.Hippocampal tissues from rats in the control group(NC group),epilepsy group(SE group),and epilepsy UA treatment group(UA group)were subjected to full-length transcriptome sequencing.The obtained sequencing data were analyzed,using gene ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and protein-protein interaction(PPI)to perform the analysis of differential genes(DEGs).The expression levels of key differential genes were verified using RT-qPCR in hippocampal tissue.Finally,an epilepsy in vitro model was constructed on primary neurons,RT-qPCR was used to verify the expression levels of key differential genes,and the expression level of GABAA receptor γ2 subunit(GABRG2)on neurons was further examined using immunofluorescence and Western blot.The heatmap of pairwise sample expression correlation and the clustering analysis of differentially expressed genes showed that the SE group was farthest from the NC group,and that after UA treatment,the overall trend shifted towards the normal group.Compared with the SE group,a total of 220 differential genes were screened in the UA group,including 143 upregulated genes and 77 downregulated genes.GO enrichment analysis showed that it involved three processes in the primary classification:biological processes,cellular components,and molecular functions.KEGG pathway enrichment analysis showed that DEGs were involved in 36 biological pathways,including cAMP signaling pathway and calcium signaling pathway.PPI analysis showed that DEGs were closely related to GABA and inflammation.RT-qPCR results showed that UA treatment increased the expression levels of GABA receptor-related gene(Gng4),GABA synthesis-related gene(Camk2a,Vgf,and Npy)and inflammation-related gene(Timp1 and Spp1)in hippocampal tissue,and decreased the expression levels of GABA synthesis-related gene(Nptx2)and cAMP-related pathway gene(Gnas).It further confirmed that UA treatment increased the expression levels of Gng4 and Camk2a on neurons and decreased the expression level of Gnas.Immunofluorescence and Western blot results showed that,compared with the SE group,the expression level of GABRG2 on primary neurons increased after UA treatment.This study enriched the transcriptome data of UA's antiepileptic effect and laid a theoretical foundation for further research on UA's antiepileptic and neuroprotective effects.

Objective To investigate the mechanism of gastrodin for inhibiting microglia-mediated inflammation after hypoxic-ischemic brain damage(HIBD)in neonatal rats.Methods Thirty-nine 3-day-old SD rats were randomly divided into sham group,HIBD group and gastrodin treatment group.Western blotting was used to detect the expressions of TNF-α,IL-1β,IL-10 and TGF-β1 in the corpus callosum of the rats.The potential targets of gastrodin for treatment of HIBD were screened by network pharmacology analysis.The expressions of PI3K/AKT signaling pathway proteins following HIBD-induced microglial activation in the rats and in cultured microglial BV-2 cells with oxygen-glucose deprivation(OGD)were detected with Western blotting.The effects of LY294002(a specific inhibitor of the PI3K/AKT pathway)and gastrodin on TNF-α and TGF-β1 mRNA levels in BV-2 cells with OGD was detected with RT-qPCR.Results In the neonatal rats with HIBD,gastrodin treatment significantly decreased TNF-α and IL-1β expressions and enhanced IL-10 and TGF-β1 expressions in the ischemic corpus callosum.Network pharmacology analysis showed significant enrichment of the PI3K/AKT signaling pathway and a strong binding between gastrodin and PI3K.Gastrodin significantly promoted PI3K and AKT phosphorylation in neonatal rats with HIBD and in BV-2 cells exposed to OGD.In BV-2 cells with OGD,gastrodin obviously suppressed OGD-induced increase of TNF-α and reduction of TGF-β1 mRNA expressions,and this effect was strongly attenuated by LY294002 treatment.Conclusion Gastrodin can inhibit microglia-mediated inflammation in neonatal rats with HIBD by regulating the PI3K/AKT signaling pathway.

Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.