Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

Objective To understand the implementation of the nursing group standards for oxygen inhalation therapy in clinical practice,and to provide a reference for improving the nursing practice of oxygen therapy.Methods A convenience sampling method was used to investigate nurses from 902 hospitals in 24 provinces and municipalities directly under the central government using a self-designed questionnaire from December 15th,2022,to January 14th,2023.The content of questionnaire included whether they had implemented the recommendations of the oxygen therapy standards,the knowledge of safety related to oxygen therapy,and the components of oxygen therapy prescriptions,the indications used for patients receiving oxygen therapy and practice status of oxygen therapy.Results A total of 10481 questionnaires were returned,of which 10447 were valid,with a valid questionnaire recovery rate of 99.68%.63.14%of the nurses indicated that the hospital had organized training on oxygen therapy standards.Only 47.82%of nurses know the correct use of the Venturi mask.41.90%of nurses could indicate the correct indicator of flow adjustment.31.88%of the nurses stated that they will adjust the oxygen flow rate based on the oxygenation status of carbon dioxide storage patients.Only 19.56%of nurses indicated that humidification is applied in oxygen therapy based on the oxygen flow and duration.Conclusion Even though nurses had received training related to oxygen therapy standards,the level of knowledge of oxygen therapy standards was still low;therefore continuous systematic training was needed,and the implementation of the content of oxygen therapy standards needed to be further standardized.Healthcare institutions would focus on organizing systematic training and maintaining the training effect,enhancing infrastructure and providing support for implementation.Recommendation to the nursing administration is to explore how to comprehensively and continuously implementing the oxygen therapy nursing standards with the ultimate goal of providing patients safer and more accurate oxygen therapy.

The World Health Organization (WHO) classification serves as the internationally recognized standard for diagnosing and classifying hematopoietic and lymphoid tissue tumors(WHO-HEAM). Since 2001, it has undergone multiple upgrades and revisions, updating, clarifying, and refining previous tumor diagnostic and classification standards while incorporating numerous new genetic and molecular biological subtypes. In 2022, two classification proposals emerged due to a wealth of clinical and scientific research results: the fifth edition of the WHO hematopoietic and lymphoid tissue classification (WHO-HAEM5), published in Leukemia journal; and the International Consensus Classification (ICC), published in Blood journal. These two schemes differ in their approach to classifying hematopoietic and lymphoid tissue tumors, posing challenges for clinical laboratory diagnosis and treatment.

Objective To evaluate the clinical efficacy and safety of modified Weijing Decoction in the treatment of stable stage of bronchiectasis(phlegm heat accumulating in the lung pattern).Methods A series of N-of-1 trials using bronchiectasis patients in stable stage with phlegm heat accumulation in the lung pattern were performed.Participants meeting inclusion criteria underwent two distinct treatment protocols during a therapy period.Modified Weijing Decoction was used in the experimental period and ambroxol tablets were used in the control period,washout periods were set.The medication-use order in the control period and experimental period is random.The visual analog scale(VAS)was used to assess symptom changes before and after treatment.24-hour sputum volume and COPD self-assessment test(CAT)scores were recorded,while adverse reactions were monitored during the study period.Statistical analysis and drawing were performed on SPSS 25.0 and GraphPad Prism 8.Comparison of inter-group differences before grouping was assessed by independent samples t-test.Analysis of symptom score,24-hour sputum volume and CAT scores in the experimental and control periods,as well as comparison of differences between the above two groups before and after treatment were performed using paired t-test,which enabled comprehensive exploration of clinical and statistical distinctions.Results A total of 9 patients participated in 16 rounds of analysis.Statistically significant differences(P＜0.05)before and after the treatment in the experimental period were noted in total Traditional Chinese Medicine(TCM)symptom scores,cough,sputum,sputum color,chest tightness and chest pain,bitter and dry mouth,fatigue and tiredness,24-hour sputum volume,and CAT score.Paired t-tests revealed significant variations(P＜0.05)in the total TCM symptom scores,sputum color scores,scores of chest tightness and pain,and 24-hour sputum volume between experimental and control periods.No adverse events related to the test methods or drugs occurred during the observation period.Conclusion Modified Weijing Decoction could comprehensively improve clinical symptoms of bronchiectasis patients in stable stage.It exhibits superior efficacy compared to ambroxol,and maintains a favorable safety profile.

Innate immunity is the front line of the antiviral immune response and the bridge to a-daptive immunity.Porcine reproductive and respiratory syndrome virus(PRRSV)has evolved mul-tiple strategies to evade the host's innate immunity and thus establish persistent infections,which is one of the biggest obstacles to control PRRSV infection.In antiviral innate immunity,type Ⅰ in-terferons,interferon-stimulated genes(ISGs),and other antiviral proteins are the main perform-ers,cellular autophagy and programmed cell death are important components,noncoding RNAs are key regulators.Studies on evasion mechanisms of innate immune by PRRSV have emerged in re-cent years,greatly expanding our understandings of the PRRSV-host interaction network.In this paper,we outline the latest researches on PRRSV inhibition of type Ⅰ interferon production and its signaling transduction as well as antagonism of ISGs and other antiviral proteins,and focus on summarizing the researches on PRRSV evade the innate immunity through the modulation of cel-lular autophagy,programmed cell death,and non-coding RNAs,with a view to providing ideas for subsequent research and anti-PRRSV vaccine and drug development.

Objective The goals of this study were to identify early warning markers of severe dengue based on bioinformatics com-bined with machine learning,and explore the evaluation system of the risk of occurrence of severe dengue.Methods Based on the Gene Expression Omnibus database,the differentially expressed genes between dengue and severe dengue were analyzed,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted.Early warning genes of severe dengue were screened using a random forest model,and the accuracy of the genes was verified using receiver operating characteristic(ROC)curves.Finally,nomograms were constructed to quantify the warning genes and predict the risk of progression from dengue to severe dengue based on the expression level of these genes.Results A total of 817 differentially expressed genes were identified,along with the associated biolo-gical processes that may be closely related to the occurrence and development of severe dengue,namely,antimicrobial humoral response,humoral immune response,serine hydrolase activity,and arachidonic acid metabolism.Based on this analysis,five early warning genes were isolated:AZU1,PDCD4,COL4A3BP,TRPM4,and ATP4A.Among these,ATP4A,COL4A3BP,and TRPM4 showed low expression levels,whereas AZU1and PDCD4were highly expressed.The ROC curves indicated that these genes were accurate pre-dictors of severe dengue.The nomograms indicated good predictive accuracy,clinical benefit rate,and clinical effectiveness of the model.Conclusion Measuring the expression levels of five warning genes(AZU1,PDCD4,COL4A3BP,TRPM4,and ATP4A)may help to evaluate the risk of severe dengue.

Objective:To explore the clinical manifestations, auxiliary examinations, treatment, and outcomes of autoimmune-associated epilepsy (AAE) with anti-glutamic acid decarboxylase 65 (GAD65) antibodies.Methods:Nine patients diagnosed with AAE with anti-GAD65 antibodies between July 2019 and December 2023 at the Department of Neurology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, were enrolled. Their clinical data and prognosis were retrospectively analyzed.Results:The onset age of these 9 cases was 13.0-59.0 (29.0±13.4) years, with 8 females and 1 male. The main clinical phenotypes at onset included limbic encephalitis/extralimbic encephalitis (6 cases) and chronic epilepsy (3 cases, of whom 1 case was accompanied with stiff person syndrome). The former often demonstrated T 2/fluid attenuated inversion recovery (FLAIR) hyperintensities and enlargement of hippocampus and amygdala (5 cases), and may present with concomitant meningoencephalitis (2 cases) or hypertrophic pachymeningitis (1 case). The latter showed normal (2 cases) or increased T 2/FLAIR signals in the hippocampal tails (1 case) in magnetic resonance imaging. Electroencephalogram findings were usually characterized by slow activities (6 cases) and temporal epileptiform discharges (6 cases). Five cases concurrently presented with one or more other autoimmune diseases, including the autoimmune polyendocrine syndrome type Ⅱ in 1 case. All cases received first-line immunotherapy and 7 cases received long-term immunosuppressive agents. Eight cases were followed up for 5-45 months and 2 cases experienced relapse of autoimmune encephalitis (presented with new-onset seizures). At the last follow-up, all cases achieved favourable outcomes according to the modified Rankin Scale scores (all≤2) and 4 patients had reduced seizures, of whom 2 were seizure-free. Conclusions:Anti-GAD65 antibody-positive AAE is mainly composed of postencephalitic epilepsy and chronic temporal lobe epilepsy. The co-occurrence of systemic autoimmune diseases is common, and meningeal lesions sometimes can be involved in MRI findings. Patients usually have poor response to immunotherapy and anti-seizure medication,and some postencephalitic epilepsy patients who receive early immunotherapy and long-term immunosuppressants can achieve sustained seizure freedom.

Objective:To investigate the application value of small private online course (SPOC) based on the concept of outcomes-based education (OBE) in rehabilitation nursing training for elderly patients after lumbar surgery.Methods:A total of 46 clinical nurses in Department of Spinal Surgery in our hospital were selected as subjects, and they were divided into control group and observation group using a simple random number table, with 23 nurses in each group. The nurses in the control group were trained by the traditional teaching method, while those in the observation group were trained by SPOC teaching based on the educational concept of OBE. The two groups were assessed in terms of the effect of training, professional core competencies, and degree of satisfaction with the training mode. SPSS 22.0 was used to perform the chi-square test and the t-test. Results:Compared with the control group, the observation group had significantly better overall evaluation [（89.52±5.07）vs.（86.48±4.13）], mastery of practical operation skills (91.30% vs. 65.22%), and proficiency in the operation of commonly used clinical instruments (95.65% vs. 80.95%)( P<0.05). The observation group had a significantly better score of the professional core competence scale than the control group ( P<0.05). Compared with the control group, the observation group had a significantly higher degree of satisfaction with the training ( P<0.05). Conclusion:In rehabilitation nursing training for elderly patients after lumbar surgery, SPOC teaching based on the educational concept of OBE can improve the training effect of clinical nurses, enhance their professional core abilities, and increase the degree of satisfaction with training.

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.