Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Objective:To understand the incidence trend of meningococcal meningitis from 1990 to 2023 and major pathogenic serogroups of Neisseria ( N.) meningitidis from 2006 to 2023 in China and the time trend of the incidence of meningococcal meningitis caused by main pathogenic serogroups, and provide reference for the prevention and control of meningococcal meningitis. Methods:The study used the data from "National Epidemic Data Compile" from 1990 to 2003 and the data from China Notifiable Infectious Disease Reporting System from 2004 to 2023 to analyze the incidence trend of meningococcal meningitis in China from 1990 to 2023 by Joinpoint regression method. Based on the data of the national meningococcal meningitis surveillance information reporting and management system from 2006 to 2023, the incidence of meningococcal meningitis caused by different serogroups of N. meningitidis was described and analyzed, and the trend χ2 test was performed to analyze the change of the incidence of meningococcal meningitis caused by N. meningitidis A, B, and C. Results:The overall incidence of meningococcal meningitis in China showed a downward trend from 1990 to 2023 [average annual percent change (AAPC)=-14.80%, P<0.001], with the most obvious decline from 2005 to 2012 [annual percent change (APC)=-31.01%, P<0.001]. The incidence of meningococcal meningitis decreased in both men and women (AAPC=-14.69% and -15.05%, both P<0.001). A total of 1 178 serogroup specific cases of meningococcal meningitis were reported in China from 2006 to 2023, the proportion of serogroup C was highest (32.5%), followed by unclassified (22.3%), B (20.1%), A (18.4%), W (4.5%), Y (2.0%) and X (0.2%). The results of trend χ2 test indicated that the incidence of meningococcal meningitis caused by N. meningitidis A and C showed downward trends (both P<0.001) and the incidence of meningococcal meningitis caused by N. meningitidis B showed an upward trend in general population and young children (0-4 years old group) from 2006 to 2023 (both P<0.05). Conclusion:The incidence of meningococcal meningitis showed a downward trend in China from 1990 to 2023, but it is still necessary to pay more attention to the incidence of meningococcal meningitis caused by N. meningitidis B in age group aged 0-4 years and by multi serogroups at same time in general population.

A method capable of retinal vessel segmentation and three-dimensional(3D)reconstruction is proposed for the early diagnosis of diabetic retinopathy.The 3D reconstruction can avoid the misjudgments of blood vessel length,curvature and branch angle after segmentation,which will affect the early diagnosis.IAAnet algorithm for retinal image segmentation combines traditional Unet with Inception V3,atrous spatial pyramid pooling and AttentionGates to reduce information loss and avoid over-fitting,thereby improving the network's ability to extract features.The projection reconstruction method is used to restore the 3D information of blood vessels,and supports the adjustments of brightness and contrast,so that doctors can better observe the real state of blood vessels.The proposed algorithm has an accuracy,recall rate,F1 score,intersection over union and area under ROC curve of 97.68%,96.07%,97.26%,92.79%and 94.00%,respectively.Compared with other networks,IAAnet algorithm exhibits higher segmentation accuracy,and can obtain more vascular information in 3D image after 3D projection reconstruction to assist in the early diagnosis.

Objective To explore the process and main behavior characteristics of behavioral characteristics of patients with recurrent hypoglycemia in the degeneracy of blood glucose management.Methods A mixed-method convergent design was used to collect data.From June 2022 to April 2023,382 patients with recurrent hypoglycemia were admitted to the endocrine department of a tertiary hospital in Jiangsu were recruited to score of ego depletion.K-means clustering was conducted to analyze the distribution characteristics of patients'characteristics in blood glucose management.At the same time,19 patients who were selected from the participants of the quantitative study were recruited to attend semi-structured interviews.Results Quantitative results analysis:the average score of blood glucose management loss was(49.20±6.58),and the average scores of cognitive control,behavioral control and emotional control were(17.90±4.12),(15.49±3.64)and(15.81±3.58),respectively.The results of cluster analysis showed that behavioral characteristics could be divided into 3 groups:a cognitive depletion group,an emotional depletion group and a self-control group.Qualitative data analysis:the process of deterioration of management in patients included 3 major themes,including the antecedents of ego depletion,the process of ego depletion and the aftereffects of ego depletion.Analysis of the mixed results showed that the status of ego depletion is serious;patients ignore the behavioral elements of active participation in blood glucose management,show many irrational decision-making behaviors,and the degradation behavior characteristics of patients'blood glucose management are different.Conclusion The degeneration behavior of blood glucose management was serious and affected by single or multiple factors,continuously consuming self-control energy and causing ego depletion.To promote the long-term maintenance of blood glucose management,priority should be given to take actions to enhance patients'perceptions,emotion and behaviors,help them learn about the possible blood glucose changes,improve their understanding and recognition of the value of scientific management.

BackgroundThe improvement of social function in patients with schizophrenia is an important part of their rehabilitation， and peer support services， as a rehabilitation method， may be of great significance to improve the social function of patients with schizophrenia. ObjectiveTo explore the influence of peer support service on the daily living ability and social function of patients with chronic schizophrenia， and to provide references for promoting the rehabilitation of patients with chronic schizophrenia. MethodsA total of 100 patients with chronic schizophrenia who were hospitalized in The Third People's Hospital of Tianshui from January 1 to December 31， 2020 and met the diagnostic criteria of the International Classification of Diseases， 10th edition （ICD-10） were selected as the study objects， and they were divided into the control group and the study group with 50 cases each by random number table method. Patients in both groups received routine treatment and nursing care， on this basis， the study group received peer support service once or twice a week for 12 weeks， and the control group received the same peer support service at the end of the study. Before and at the 1^st， 2^nd， 4^th， 8^th and 12^th week of the treatment， Activity of Daily Living Scale （ADL） and Social Disability Screening Schedule （SDSS） were used to evaluate the activities of daily living and social function of the two groups. ResultsThe ADL scores of the study group were lower than those of the control group at the 8^th week and 12^th week of the treatment （ t=-2.420， -2.814， P<0.05 or 0.01） . The SDSS scores of the study group were lower than those of the control group at the 8^th week an 12^th week of the treatment （t=-2.057， -2.322， P<0.05） . ConclusionPeer support services may help improve the ability of daily life and social function of patients with chronic schizophrenia. ［Funded by Tianshui City Livelihood Science and Technology Plan Project （number， 2020-SHFZKJK-9344）］

Objective:To investigate the complement C3a receptor 1 (C3AR1) expression in glioma and its mechanism in progressing malignancy.Methods:(1) The C3AR1 mRNA expression data and clinical information were obtained in 607 glioma patients from The Cancer Genome Atlas (TCGA) database and 656 glioma patients from Chinese Glioma Genome Atlas (CGGA) database; the differences in C3AR1 mRNA expression were analyzed among gliomas with different World Health Organization (WHO) grading. The overall survival and disease-free survival were compared between high and low C3AR1 mRNA expression patients obtained from TCGA database by Gene expression profiling interactive analysis (GEPIA). Gene body (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of C3AR1 related differentially expressed genes were performed by DAVID database. Correlation of C3AR1 mRNA expression with immune cell infiltration was analyzed using TIMER online website. (2) The brain tissues from 3 non-tumor patients and 9 glioma patients surgically resected in Department of Neurosurgery, First Affiliated Hospital of Xinxiang Medical University from January 2019 to September 2021 were collected; the C3AR1 protein expression was detected by Western blotting. (3) The in vitro cultured U87 and U251 cells were divided into negative control group and C3AR1 knockdown group ( C3AR1 being knocked down by lentivirus transfection); and CCK-8 assay, plate cloning assay and Transwell assay were used to detect the proliferation rate, number of colony formation and number of membrane penetrating cells. Western blotting was used to detect the nuclear factor-κB (NF-κB) signaling pathway protein expressions. Results:(1) In TCGA database, the C3AR1 mRNA expression in gliomas of WHO grading II, grading III and grading IV increased sequentially, with significant differences ( P<0.05). In CGGA database, the C3AR1 mRNA expression in glioma of WHO grading IV was statistically higher than that in gliomas of WHO grading II and grading III ( P<0.05). GEPIA showed that the overall survival and disease-free survival in the low C3AR1 mRNA expression group were statistically higher than those in the high C3AR1 mRNA expression group ( P<0.05). GO function analysis and KEGG pathway enrichment analysis revealed that C3AR1 related differentially expressed genes were more enriched in such biological processes and signaling pathways as calcium homeostasis, membrane structural valves, proton transmembrane transporter protein activity, chemokine signaling pathway and NF-κB signaling pathway. TIMER showed that C3AR1 mRNA expression in glioblastoma and low-grade glioma was positively correlated with infiltration degrees of B cells, CD4 + T cells, neutrophils, macrophages and dendritic cells, and C3AR1 mRNA expression in glioblastoma was negatively correlated with infiltration degree of CD8 + T cells ( P<0.05). (2) C3AR1 protein expression in glioma tissues was significantly higher than that in non-tumor tissues. (3) Compared with the negative control group, the C3AR1 knockdown group group had significantly lower proliferation rate, smaller numbers of colony formation and membrane penetrating cells, and lower expressions of NF-κB, phosphorylated (p)-NF-κB, p-NF-κB inhibitory protein (IκB)α, p-I-κB kinase (IKK)α and N-cadherin, and significantly higher E-cadherin expression. Conclusion:C3AR1 is highly expressed in glioma and progresses malignancy through NF-κB signaling pathway.

Objective:To solve the difficult problem of experimental teaching of MRI equipment by independently designing a virtual simulation teaching system for performance testing of medical magnetic resonance imaging (MRI) equipment.Methods:A total of 202 students of Batch 2016 majoring in 4-year medical imaging technology and 5-year medical imaging of Binzhou Medical University. According to the teaching requirements of MRI equipment in Medical Imaging Equipment Science, a 3D experimental simulation model and experimental scenes were established based on Unity3D engine by using Unity3D, 3D Studio Max, Maya and Visual Studio technology to design experimental learning content and assessment content, develop the teaching system software and perform Web-based online learning. Then, the satisfaction survey on experimental learning was conducted, the statistics of the experimental results of the teaching system on the national virtual simulation experiment teaching platform was collected and the learning effects were evaluated in multiple dimensions. Results:The virtual simulation teaching system was a comprehensive experiment with 12 knowledge points, 12 experimental items and a total of 81 interactive contents and steps. The overall satisfaction rate of 202 students in our school was 96.82%(2 347/2 424). Among the 499 subjects who participated in the learning of the teaching system on the national virtual simulation experiment teaching platform and submitted the experimental report, the average score of the experiment was 78.07 points (the full score of online learning assessment was 90 points), and the overall passing rate was 96.79%(483/499). The average learning time of the 18 students who got 90 points was 54 min.Conclusion:This virtual simulation teaching system possesses comprehensive experimental contents with high fidelity of experimental scenes and strong interactivity of experimental operation, prospecting great learning effects and promotion value.

We researched the mechanism of African swine fever virus (ASFV) protein E248R in regulating the cGAS-STING pathway. First, we verified via the dual-luciferase reporter assay system that E248R protein inhibited the secretion of IFN-β induced by cGAS-STING or HT-DNA in a dose-dependent manner. The relative quantitative PCR analysis indicated that the overexpression of E248R inhibited HT-DNA-induced transcription of IFN-b1, RANTES, IL-6, and TNF-α in PK-15 cells. Next, we found that E248R interacted with STING by co-immunoprecipitation assay and laser confocal microscopy. Finally, we demonstrated that E248R inhibited the expression of STING protein by using Western blotting. We demonstrated for the first time that the E248R protein of ASFV suppressed the host innate immune response via inhibiting STING expression. The results are pivotal in extending the understanding of the ASFV immune escape and can guide the design of vaccines against ASFV.
African Swine Fever Virus/genetics* ; Animals ; DNA ; Immunity, Innate ; Nucleotidyltransferases/metabolism* ; Signal Transduction ; Swine

The Delta variant of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a new global wave of the Coronavirus Disease 2019 (COVID-19) pandemic. COVID-19 vaccines currently available in China show high effectiveness against severe illness and death. However, transmission of the virus is not fully stopped by vaccination alone, therefore, integrated vaccination and non-pharmacological interventions is necessary to prevent and control the epidemic in the near future. Further expanded vaccine coverage of primary doses as well as booster shots in China's domestic population are needed to reduce severe illness and death. In order to provide evidence necessary for adjusting and optimizing immunization strategies and pandemic control measures, it is essential to conduct research on vaccine effectiveness against emerging variants, persistence of vaccine-induced protection, surveillance of adverse event following immunization with large-scale vaccine use, and modelling studies on strategic combinations of vaccination and non-pharmacological interventions.
COVID-19 ; COVID-19 Vaccines ; China ; Humans ; Immunization, Secondary ; SARS-CoV-2 ; Vaccination ; Vaccine Efficacy

In order to screen African swine fever virus (ASFV) diagnostic antigen with the best enzyme linked immunosorbent assay (ELISA) reactivity. By establishing the ELISA method, the diagnostic antigen of ASFV p30 protein expressed by baculovirus-insect cell expression system as reference, we explored the antigenic properties and diagnostic potential of ASFV p35 protein expressed by prokaryotic expression system as a diagnostic antigen. The results of Western blotting and immunofluorescence show that the molecular weight of the recombinant p35 protein and p30 protein obtained was 40 kDa and 30 kDa, respectively, and these two proteins had good immuno-reactivity with ASFV positive serum. Recombinant p30 and p35 proteins were used as diagnostic antigens to establish ELISA, and the sensitivity and repeatability of these methods were tested. The results show that although the detection sensitivity of the p30-ELISA established in this study was higher than that of the p35-ELISA, the sensitivity of p35-ELISA was 95.8%, and variations in intra- and inter-assay repeatability of the two methods were less than 10%. The coincidence rate between the p35-ELISA and the imported kit was 97.2%. Results show that p35-ELISA was sensitive and stable, and could detect specific antibodies against ASFV.
African Swine Fever/diagnosis* ; African Swine Fever Virus/genetics* ; Animals ; Antibodies, Viral ; Enzyme-Linked Immunosorbent Assay ; Recombinant Proteins/genetics* ; Swine