ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Objective To construct the training program for the digital and intelligent capabilities of specialized nurses in the Central Sterile Supply Department(CSSD),and conduct preliminary practice to provide talent support for the intelligent development of CSSD.Methods From February to April 2024,based on the core technologies of digital intelligence and related core capabilities,a training program for digital intelligence-related competencies of CSSD specialized nurses was constructed using literature review and the Delphi expert consultation method.From July to August 2024,the program was initially implemented in the training of CSSD specialized nurses.The nurses'information competency before and after the training was compared,and the nurses' satisfaction with the digital intelligence-related training program was assessed.Results This study conducted 2 rounds of expert consultation via questionnaire.The effective recovery rate of the questionnaires in both rounds was 100％.The expert authority coefficients were 0.790 and 0.800,respectively,and the variation coefficients ranged from 0 to 0.229 and 0 to 0.105.Ultimately,a training program for the digital-related competencies of CSSD specialty nurses was established,which includes 4 components:training objectives,training content,training methods,and assessment methods.Specifically,there were 3 indicators at the first level and 14 at the second level for training objectives,6 indicators at the first level and 32 at the second level for training content,and 6 indicators at the first level for training methods and assessment methods.After the implementation of the training program,the information competency of the nurses in all dimensions and the total score were significantly higher than those before training(P＜0.05).Moreover,the average scores for the training content,training methods,and assessment methods were all above 3 points,indicating a high overall satisfaction among the nurses.Conclusion The construction process of the training program for the digital and intelligent capabilities of CSSD specialty nurses is scientific and reliable.The content is highly practical and distinctive in its specialty.The training methods and assessment approaches are diverse.This program can enhance nurses' information competency and provide a reference for the implementation of digital and intelligent training for CSSD specialty nurses.

Metabolic diseases such as childhood and adolescent obesity,type 2 diabetes have become urgent public health challenges that need to be addressed.Endothelial dysfunction is considered as a precursor event of cardiovascular disease,and its prevention and treatment have become an essential focus of health management.Being obese and spend-ing less time exercising in children and adolescents almost exist simultaneously.In this context,time-saving high-intensity interval training(HIIT)intervention is essential to prevent cardiovascular and cerebrovascular diseases in children and adolescents.This article aims to comprehensively review the latest research progress on HIIT intervention in improving vascular endothelial function in obese children and adolescents.Through systematic review and comprehensive analysis,it provides theoretical and practical guidance for future research and promotes the development and implementation of effective health interventions.

Objective To investigate the effect of programmed death-1(PD-1)on cell infiltration in muscle tissue and immune response types in mice infected with Trichinella spiralis.Methods C57BL/6J wild-type(WT)and PD-1 deficient(PD-1-/-)mice were infected with T.spiralis(400 muscle larvae per mouse),and samples were collected on day 35 after infection.The proportions of infiltrating inflammatory cells and fibroblasts around encapsulated larvae were assessed by immunohistochemistry.The expression levels of interferon-γ(IFN-γ),interleukin(IL)-4,IL-5,IL-13,and eotaxin in muscle tissue were measured using enzyme-linked immunosorbent assay.Peripheral blood and spleen were collected at different time points after infection.The percentages of CD4+IFN-γ+Th1 and CD4+IL-4+Th2 within CD4+T cells population in peripheral blood and spleen of mice were analyzed using flow cytometry.Results The proportions of eosinophils and fibroblasts among total infiltrating cells around the encapsulated larvae in the muscle of PD-1-/-mice were significantly lower than those in WT mice after T.spiralis infection(P＜0.01).The infected PD-1-/-mice exhibited higher proportions of macrophages,T cells and B cells in total infiltrating cells than the infected WT mice(P＜0.01).The levels of IL-4,IL-5,IL-13,and eotaxin in the muscle tissue of infected PD-1-/-mice were significantly lower than those in infected WT mice(P＜0.05).However,IFN-γ levels were not significantly different between the infected WT and PD-1-/-mice.The proportions of Th2 cells in CD4+T cells from peripheral blood and spleen of infected PD-1-/-mice were significantly lower than those in infected WT mice,whereas the proportion of Th1 cells showed no difference among the infected groups.Conclusions PD-1 deletion results in decreased expression of key chemokines of eosinophils and key cytokines of fibroblast formation,and a corresponding decrease in inflammatory cells in muscle in T.spiralis-infected mice.This effect may be associated with a diminished Th2 immune response caused by PD-1 deletion.

Objective:To evaluate the efficacy of shockwave therapy,acupuncture,hyperthermia,biofeedback therapy,elec-trical nerve stimulation,magnetotherapy and ultrasound therapy in the treatment of chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS),and to provide evidence-based support for clinical decision-making.Methods:Two researchers independently searched PubMed,Web of Science,Embase,Cochrane Library,CNKI,Wanfang,VIP and Chinese Biomedical Literature databases for randomized controlled trials(RCTs)on the effects of different interventions on CP/CPPS from the establishment of the databases to August 2024.We evaluated the quality of the included literature and extracted the relevant data according to the Cochrane Handbook for Systematic Reviews of Interventions,followed by network meta-analysis using Revman 5.3,R 4.33 and Stata17 software.Results:A total of 25 RCTs involving 1 794 cases were included.The results of network meta-analysis showed that electrical nerve stimulation,shockwave therapy,biofeedback therapy,magnetotherapy,ultrasound therapy and acupuncture were significantly superior to conventional medication and placebo in the total NIH-CPSI scores(P＜0.05),and so were electrical nerve stimulation and shock-wave therapy to acupuncture and hyperthermia(P＜0.05),magnetic therapy to hyperthermia,and ultrasound therapy to placebo(P＜0.05).Shockwave therapy,biofeedback therapy,electrical nerve stimulation,magnetotherapy and ultrasound therapy achieved re-markably better clinical efficacy than conventional medication and placebo in the treatment of CP/CPPS,and so did shockwave therapy than electrical nerve stimulation,hyperthermia,ultrasonic therapy,magnetotherapy and acupuncture.Conclusion:For the treat-ment of CP/CPPS,electrical nerve stimulation is advantageous over the other interventions in improving total NIH-CPSI scores,and shockwave therapy is advantageous in relieving pain symptoms and clinical efficacy.This conclusion,however,needs to be further veri-fied by more high-quality clinical studies.

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

Objective:To improve the awareness of Beh?et′s disease with ventricular neoplasm.Methods:A case with fever, thrombosis, and right ventricular neoplasm was described. The diagnosis and treatment were analyzed and discussed.Results:A young male with genital ulcers and oral ulcers, ocular, skin, and vascular lesions presenting as large venous thrombus, was diagnosed with Beh?et′s disease. Pathological results of space-occupying lesion in right ventricle revealed inflammation and necrotic substance. Endocarditis was considered. Glucocorticoids and cyclophosphamide was given, together with warfarin. During one-year follow-up, the patient remained stable.Conclusion:It is difficult to distinguish between Beh?et′s disease with cardiac neoplasm and infective endocarditis or cardiac tumor based on clinical manifestations and imaging only. Multidisciplinary management is a valuable approach for the diagnosis and treatment.

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C

The efficacy of Xiangmei Pills on rats with ulcerative colitis(UC) was investigated by characterizing the spectrum of the active chemical components of Xiangmei Pills. Rapid identification and classification of the main chemical components were performed,and the therapeutic effects of Xiangmei Pills on the proteins and intestinal flora of UC rats were analyzed to explore the mechanism of its action in treating UC. Fifty SD rats were acclimatized to feeding for 3 d and randomly divided into blank group, model group,mesalazine group(0. 4 g·kg~(-1)), low-dose group of Xiangmei Pills(1. 89 g·kg~(-1)), and high-dose group of Xiangmei Pills(5. 67 g·kg~(-1)), with 10 rats in each group. 5% dextrose sodium sulfate(DSS) was given by gavage to induce the male SD rat model with UC,and the corresponding medicinal solution was given by gavage after 10 days, respectively. The therapeutic effect of Xiangmei Pills on rats with UC was evaluated according to body mass, disease activity index(DAI), and hematoxylin-eosin(HE) staining, and the histopathological changes in the colon were observed. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) technique was used to rapidly and accurately identify the main chemical constituents of Xiangmei Pills. Immunohistochemistry was used to detect the expression of aryl hydrocarbon receptor(AhR),interferon-γ(IFN-γ), mucin-2(MUC-2), and cytochrome P450 1A1(CYP1A1) in colon tissue. Interleukin-22(IL-22) expression in colon tissue was detected by immunofluorescence. The 16S r DNA high-throughput sequencing technique was used to study the modulatory effects of Xiangmei Pills on the intestinal flora structure of rats with UC. Pharmacodynamic results showed that compared with that of the blank group, the colon tissue of the model group was congested, and ulcers were visible in the mucosa; compared with that in the model group, the histopathology of the colon of the rats with UC in the groups of Xiangmei Pills were improved, with scattered ulcers and reduced inflammatory cell infiltration. Chemical analysis showed that a total of 45 components were identified by mass spectrometry information, including 15 phenolic acids, 8 coumarins, 15 organic acids, 3 amino acids, 2 flavonoids, and 2 other components. Compared with those in the blank group, the levels of Ah R, CYP1A1, MUC-2, and IL-22 proteins in the colon tissue of rats in the model group were significantly decreased, and the level of IFN-γ protein was significantly increased; the intestinal flora of rats in the model group was disorganized, with a decrease in the abundance of the flora; the relative abundance of Bacteroidetes,unclassified genera of Ascomycetes, Prevotella of the Prevotella family, and Prevotella decreased significantly, and that of Firmicutes decreased, but the difference was not statistically significant. The relative abundance of Bacteroidetes, Bifidobacterium, and Lactobacillus increased significantly. Compared with those of the model group, the levels of Ah R, CYP1A1, MUC-2, and IL-22proteins in the colonic tissue of the groups of Xiangmei Pills were significantly higher, and the levels of IFN-γ proteins were significantly lower. The recovery of the intestinal flora was accelerated, and the diversity of the intestinal flora was significantly increased. The relative abundance of Bacteroidetes was significantly increased, and that of unclassified genera of Ascomycetes,Lactobacillus, Prevotella of the Prevotella family, and Prevotella was significantly increased. The relative abundance of Bacteroidetes and Bifidobacterium was significantly decreased. This study demonstrated that Xiangmei Pills can effectively treat UC, mainly through the phenolic acid and organic acid components to stimulate the intestinal barrier, regulate protein expression and the relative abundance and diversity of intestinal flora, and play a role in the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Male ; Rats ; Gastrointestinal Microbiome/genetics* ; Chromatography, High Pressure Liquid ; Humans ; Mass Spectrometry ; RNA, Ribosomal, 16S/genetics* ; Bacteria/drug effects*