Objective:To construct a nanoparticle vaccine displaying the prefusion F (preF) protein of respiratory syncytial virus (RSV) using the I53-50 protein nanoparticle platform, and to systematically evaluate its immunogenicity and protective efficacy.Methods:The RSV preF trimer antigen was genetically fused to I53-50A and assembled in vitro with I53-50B to form preF-I53-50 nanoparticles, theoretically displaying 20 preF antigens per particle. The structure and purity were characterized by size-exclusion chromatography, SDS-PAGE, and negative-stain electron microscopy. BALB/c mice were intramuscularly immunized with varying doses (1 μg or 5 μg) of preF antigen or an equimolar amount of preF-I53-50 nanoparticles. Humoral immunity, B-cell responses, and protective efficacy were assessed following intranasal viral challenge.Results:The preF-I53-50 nanoparticles self-assembled into spherical structures (50-60 nm in diameter) with uniformly arrayed antigens. The nanoparticle vaccine enhanced RSV-specific IgG1 and IgG2a antibody responses, promoting a Th1-biased immune profile. At equimolar preF doses, the neutralizing antibody titers induced by 1 μg and 5 μg nanoparticle formulations were 2.8-fold and 2.3-fold higher, respectively, than those elicited by preF alone ( P<0.05). Notably, even the low-dose nanoparticle group outperformed the high-dose preF group (1.6-fold increase). Viral challenge experiments demonstrated that preF-I53-50 effectively suppressed pulmonary viral replication, mitigated pathological damage, and induced stronger germinal center and memory B-cell responses, suggesting enhanced B-cell affinity maturation and long-term immune memory. Conclusion:The preF-I53-50 vaccine improves the immunogenicity and protective efficacy of RSV preF through multivalent antigen display.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Thirty SPF Kunming male mice aged 6-8 weeks were randomly divided into five groups:the control group,the model group,and the low,medium,and high dose groups of Dilong.Except for the control group,the other mice were continuously injected intraperitoneally with 80 mg/kg cyclophosphamide for 3 days to prepare an immunosuppressive model.After the model-ing was completed,the control group and the model group were given an equal amount of physio-logical saline by gavage,while the low,medium,and high dose Dilong groups were given 100,200,and 400 mg/kg of Dilong fermented material by gavage,respectively.The treatment lasted for 14 days,and thymus,spleen,blood,and intestinal contents were collected 2 hours after the last admin-istration.The results showed that cyclophosphamide caused a weight loss in mice during the exper-iment,reduced thymus index,white blood cells,lymphocytes,granulocytes,immunoglobulin levels in the blood,and disrupted gut microbiota.Dilong fermented material can effectively improve the decrease in body weight and thymus index of mice,increase the levels of immune cells and immu-noglobulin in the blood,improve the diversity and richness of intestinal microbiota,and increase the abundance of beneficial bacteria.Dilong fermented can effectively alleviate the immune suppres-sion and intestinal microbiota disorder caused by cyclophosphamide in mice.Considering all fac-tors,the optimal dosage is 200 mg/kg.

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

Abstract Alzheimer′s disease(AD) is a common neurodegenerative disease. It has been found that AD is related to various pathogenic factors such as genetics, cardiovascular and cerebrovascular disease, and excessive phosphorylation of tau protein. However, no definitive conclusions on its pathogenesis have been reached. In this paper, the research progress on the pathogenesis of AD inC.elegansmodel and the therapeutic effects of traditional Chinese medicine extracts on AD are reviewed, providing a basis for further research on the alleviating effects of Chinese medicine extracts on AD.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

External apical root resorption(EARR)is one of the most common side effects of orthodontic treatment.Contact with sur-rounding anatomical structures during tooth movement is a significant cause for EARR.However,a comprehensive review of factors leading to EARR due to direct contact of surrounding anatomical structures with the root apex during orthodontic treatment is still lac-king.This review summarizes the anatomical structures related to EARR,including alveolar bone,incisive canal,maxillary sinus,ad-jacent teeth,and bone islands.Alveolar bone,incisive canal,and adjacent teeth can directly cause EARR during orthodontic treat-ment,while the impact of the maxillary sinus and bone islands on EARR has not been discovered so far.Analyzing the anatomical structures around the tooth roots can help develop more effective methods to prevent or reduce the occurrence of EARR during orthodon-tic treatment.

Objective To investigate the features of resting-state electroencephalography(EEG)in stroke patients with limited upper limb movement,and assess its potential utility in evaluating upper limb motor function.Methods From March to August,2024,a total of 71 stroke patients with limited upper limb movement were enrolled as stroke group at the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine;while 63 healthy participants matched for age and sex were recruited as control group.They were tested with 19-chan-nel resting-state EEG(rsEEG),calculating of the pairwise derived brain symmetry index(pdBSI)and Delta/Al-pha ratio(DAR).The motor function was assessed with Fugl-Meyer Assessment-Upper Extremities(FMA-UE),the upper limb recovery was evaluated with Brunnstrom Stages and the activities of daily living was assessed with modified Barthel index(MBI)in stroke patients,Results Compared with the control group,the pdBSI of Global lead,Frontal region,Central region and Posterior region across Delta,Alpha and Beta1 frequency bands were significantly higher in the stroke group than in the control group(|Z|>2.289,P<0.05);as well as the pdBSI of Global lead,Central region and Posterior region across The-ta bands(|Z|>3.016,P<0.01),the pdBSI of Global lead,Frontal region,Central region and Posterior region across Beta2 bands(|Z|>3.222,P<0.01),DAR of Global lead,Frontal region,Central region and Posterior re-gion(|Z|>6.565,P<0.001).In the stroke group,the pdBSI of Global lead(r=-0.280,P=0.018)and Central region(r=-0.304,P=0.010)across the Delta band were significantly negatively correlated with FMA-UE,as well as the pdBSI of Global leads(r=-0.289,P=0.014),Central region(r=-0.244,P=0.040)and Posterior region(r=-0.356,P=0.002)across the Beta1 band,and the DAR of Global lead(r=-0.431,P<0.001),Fron-tal region(r=-0.429,P<0.001),Central region(r=-0.491,P<0.001)and Posterior region(r=-0.482,P<0.001).Conclusion Asymmetry in spectral power between hemispheres in the Delta(0.5 to 4 Hz)and Beta(13 to 20 Hz)bands is found in stroke patients,especially in the central region,which correlates with upper limb function limitations.pdBSI Delta,pdBSI Beta1 and DAR are potential neuroelectrophysiological markers for assessing upper limb motor function in stroke patients.

Thirty SPF Kunming male mice aged 6-8 weeks were randomly divided into five groups:the control group,the model group,and the low,medium,and high dose groups of Dilong.Except for the control group,the other mice were continuously injected intraperitoneally with 80 mg/kg cyclophosphamide for 3 days to prepare an immunosuppressive model.After the model-ing was completed,the control group and the model group were given an equal amount of physio-logical saline by gavage,while the low,medium,and high dose Dilong groups were given 100,200,and 400 mg/kg of Dilong fermented material by gavage,respectively.The treatment lasted for 14 days,and thymus,spleen,blood,and intestinal contents were collected 2 hours after the last admin-istration.The results showed that cyclophosphamide caused a weight loss in mice during the exper-iment,reduced thymus index,white blood cells,lymphocytes,granulocytes,immunoglobulin levels in the blood,and disrupted gut microbiota.Dilong fermented material can effectively improve the decrease in body weight and thymus index of mice,increase the levels of immune cells and immu-noglobulin in the blood,improve the diversity and richness of intestinal microbiota,and increase the abundance of beneficial bacteria.Dilong fermented can effectively alleviate the immune suppres-sion and intestinal microbiota disorder caused by cyclophosphamide in mice.Considering all fac-tors,the optimal dosage is 200 mg/kg.