Objective To investigate the correlation between lipoprotein-associated phospholipase A2(Lp-PLA2),hemoglobin glycotion index(HGI)and the severity of type 2 diabetic retinopathy.Methods A total of 120 patients with type 2 diabetes mellitus who were hospitalized in the General Hospital of Hunan Medical University from January 2021 to June 2022 were selected and divided into type 2 diabetes without retinopathy group(NDR group,n=45),non-proliferative diabetic retinopathy group(NPDR group,n=45)and prolifera-tive diabetic retinopathy group(PDR group,n=30).In the same period,50 healthy subjects were randomly selected as control group.The clinical data,Lp-PLA2 and HGI levels of each group were collected and com-pared,and the correlation between different HGI and Lp-PLA2 levels and the severity of the disease was ana-lyzed.Results The levels of Lp-PLA2 and HGI in NDR,NPDR and PDR groups were higher than those in control group(P＜0.05).The proportion of patients with NPDR and PDR in high-Lp-PLA group(H-Lp-PLA2 group)and high-HGI group(H-HGI group)were higher than those in low-HGI group(L-HGI group)and low-Lp-PLA2 group(L-Lp-PLA2 group),and the differences were statistically significant(P＜0.05).Multiple Logistic regression analysis showed that Lp-PLA2 and HGI were risk factors for DR(P＜0.05),and were positively correlated with the severity of type 2 diabetic retinopathy(P＜0.05).Conclusion HGI and Lp-PLA2 are closely related to the severity of retinopathy in type 2 diabetes mellitus,and may be used as new indicators to predict the severity of the disease.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Laccases (LACs), belonging to the multicopper oxidase family, are closely associated with various biological functions including lignin synthesis and responses to biotic and abiotic stresses in plants. However, few studies have reported the laccase genes in China rose (Rosa chinensis). Prickles cause difficulties to the management and harvest of R. chinensis and have become a trait concerned in the breeding. To investigate the expression patterns of laccase genes in roses, we cloned a laccase gene from an ancient variety R. chinensis 'Old Blush' and named it RcLAC15. The expression level of RcLAC15 in prickles was significantly higher than those in roots, stems, and leaves. Fifty-eight laccase genes were identified in the genome of R. chinensis, and bioinformatics analysis revealed that RcLAC15 was a homolog of AtLAC15, predicting that RcLAC15 was a stable hydrophilic protein without transmembrane structures. The recombinant expression vector pBI121-proRcLAC15:: GUS was introduced into Arabidopsis, and GUS staining results showed that the RcLAC15 promoter specifically drove GUS gene expression at the edges of Arabidopsis leaves. In summary, RcLAC15 is a gene specifically expressed in the prickles of R. chinensis. This discovery provides a reference for exploring the biological functions of laccase genes in the prickles of R. chinensis.
Laccase/metabolism* ; Rosa/enzymology* ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Arabidopsis/metabolism* ; Plants, Genetically Modified/metabolism*

BACKGROUND: Macrophage polarization anomalies and dysfunction play a crucial role in the pathogenesis of immune thrombocytopenia (ITP). Itaconate is a Krebs cycle-derived immunometabolite synthesized by myeloid cells to modulate cellular metabolism and inflammatory responses. This study aimed to evaluate the immunoregulatory effects of an itaconate derivative on macrophages in patients with ITP. METHODS: Peripheral blood-derived macrophages from patients with ITP and healthy controls were treated with 4-octyl itaconate (4-OI), a derivative of itaconate that can penetrate the cell membrane. Macrophage polarization, antigen-presenting functions, and phagocytic capability were measured via flow cytometry and enzyme-linked immunosorbent assay (ELISA). Macrophage glycolysis in patients with ITP and the metabolic regulatory effect of 4-OI were detected using a Seahorse XFe96 Analyzer. An active murine model of ITP was used to evaluate the therapeutic effects of 4-OI in vivo . RESULTS: 4-OI reduced the levels of CD80 and CD86 in M1 macrophages and suppressed the release of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 pro-inflammatory cytokines, suggesting that 4-OI could hinder the polarization of macrophages toward an M1 phenotype. We found that 4-OI pretreated M1 macrophages reduced the proliferation of CD4 + T cells and promoted the differentiation of regulatory T cells. In addition, after 4-OI treatment, the phagocytic capacity of M1 macrophages toward antibody-coated platelets decreased significantly in patients with ITP. In addition, the glycolytic function of M1 macrophages was elevated in individuals with ITP compared to those in healthy controls. 4-OI treatment downregulated glycolysis in M1 macrophages. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) also inhibited the polarization of M1 macrophages and restored their functions. In vivo , 4-OI treatment significantly increased platelet counts in the active ITP murine model. CONCLUSIONS Itaconate derivative 4-OI inhibited M1 macrophage polarization and restored impaired functions through metabolic reprogramming. This study provides a novel therapeutic option for ITP.
Macrophages/metabolism* ; Humans ; Animals ; Succinates/pharmacology* ; Mice ; Male ; Female ; Adult ; Middle Aged ; Flow Cytometry ; Tumor Necrosis Factor-alpha/metabolism* ; Enzyme-Linked Immunosorbent Assay ; Purpura, Thrombocytopenic, Idiopathic/metabolism* ; Glycolysis/drug effects* ; Metabolic Reprogramming

Objective To investigate the protective effect of epigallocatechin gallate(EGCG)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease model mice.Methods Twenty-eight male C57BL/6J mice aged 6～8 weeks were randomly divided into four groups:the control group,the model group,the low-dose EGCG group[25 mg/(kg·d)],and the high-dose EGCG group[50 mg/(kg·d)].A Parkin-son's disease(PD)mouse model was established by intraperitoneal injection of MPTP at a dose of 30 mg/(kg·d)for 7 consecutive days.The protective effect of EGCG on MPTP-induced Parkinson's model mice was analyzed through behavioral index detection and Western blot method.Results(1)In the behavioral tests,compared with the model group,the movement distance and speed of mice treated with low-and high-dose EGCG were significantly improved(both P values<0.001).The mice in the high-dose EGCG treatment group also showed a significant advantage in the percentage of the central path distance(P<0.001).(2)Compared with the control group,the deposition of α-synuclein in the model group increased significantly(P<0.001).Compared with the model group,both the low-and high-dose EGCG groups reduced the deposition of α-synuclein(both P<0.001).(3)Compared with the control group,the expression levels of Beclin 1 and LC3 proteins in the substantia nigra region of mice in the model group decreased significantly(both P<0.001),while the expression level of p62 protein increased significantly(P<0.001).After treatment with EGCG,compared with the model group,the expression levels of Beclin 1 and LC3 proteins in mice of the low-dose EGCG group increased to varying degrees(P<0.01;P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).In the high-dose EGCG group,the expression levels of Beclin 1 and LC3 proteins increased significantly(both P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).Conclusion EGCG reduces alpha-synuclein deposition via the autophagy-lysosomal pathway and protects against MPTP-induced Parkinson's disease model mice.

Objective To evaluate the compatibility of commonly used intravenous drugs in the ICU of Hebei General Hospital and to propose optimization strategies.Methods Data from 35 intravenous drugs used in ICU from January 1 to December 31,2023 were analyzed using the Micromedex database and relevant literature.Results A compatibility chart for 35 drugs was created.Total 595 combinations,of which 279(46.9％)were compatible,22(3.7％)were incompatible,28(4.7％)were uncertain,and 266(44.7％)were unknown.Conclusion Drug co-administration is common in the ICU,but there is a lack of safety evidence and guidelines.There is an urgent to improve compatibility data and develop comprehensive resources to ensure safer intravenous drug administration.

Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

The incidence rate of coronary atherosclerotic heart disease(commonly referred to as coronary heart disease)remains high in China.In clinical practice,drug therapy,percutaneous coronary intervention(PCI),and coronary artery bypass grafting(CABG)are commonly employed.For patients with multi-vessel coronary artery stenosis,minimally invasive interventional therapy is often the preferred option.However,for those with multi-vessel disease complicated by comorbidities,CABG is generally recommended.Despite its advantages,PCI carries risks such as vascular restenosis,thrombosis,and other adverse events.Consequently,hybrid coronary revascularization(HCR)has emerged as an alternative approach.This paper provides an overview of coronary heart disease and re-views the advantages,applications,and patient selection criteria for HCR.

Tuberculosis remains a significant global public health threat.Early diagnosis and effective treatment are crucial to combat this disease.Yet,traditional diagnostic methods for tuberculosis face limitations due to their low sensitivity,extended detection periods,and dependence on sputum samples.Molecular diagnostic techniques,while offering higher sensitivity,still primarily rely on sputum samples,thereby impeding significant advancements in tuberculosis diagnosis.In clinical settings,there exists a pressing demand for diagnostic approaches that are not solely reliant on sputum samples.In recent years,extracellular vesicles(EVs),as emerging biomarkers,have demonstrated substantial potential in various diseases,including tumors and infectious diseases.A multitude of studies indicate that EVs also exhibit potential in the field of tuberculosis.This review provides an in-depth analysis of the biological characteristics of EVs and their role in the pathogenesis of tuberculosis.It systematically summarizes the progress and significance of EV-based biomarkers in tuberculosis diagnosis,treatment monitoring,and disease mechanism exploration,while addressing the challenges and future prospects in this field.The aim is to offer valuable insights and up-to-date research findings to researchers and clinicians engaged in tuberculosis-related studies.