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Objective To explore the influence of respiratory infections on the onset of Henoch-Schönlein Purpura (HSP) in children, along with exploring potential underlying mechanisms. Method The present study conducted a statistical analysis on renal involvement indicators in 296 children with HSP who came to the Children’s Hospital of Zhejiang University, as well as the IgA levels in 400 children with respiratory infections and 400 children with HSP. Results Compared with the control group, children with HSP exhibited a significant increase in urine red blood cell count, urine microalbuminuria, and urine protein/creatinine ratio ( P  < 0.001). The monthly outpatient visits for children with respiratory infections exhibited a similar pattern to those with HSP, demonstrating a heightened prevalence during the autumn and winter. The level of IgA in children with respiratory infections and HSP were significantly higher than those in the control group ( P  < 0.001). Conclusion HSP can give rise to complications such as renal involvement. There exists a certain correlation between respiratory infections and the occurrence of HSP, which may be attributed to the elevation of IgA induced by respiratory infections. In conclusion, children with HSP should reinforce protective measures during the peak influenza season in order to prevent respiratory infections.

Chimeric antigen receptor (CAR) represents a novel targeted therapy that uses genetic engineering to modify effector cells for precise tumor cell targeting. Chimeric antigen receptor-T (CAR-T) cell immunotherapy, which employs T cells as effectors, has demonstrated significant efficacy in treating hematologic malignancies. However, its efficacy against solid tumors remains inadequate and is accompanied by toxic side effects, including cytokine release syndrome, neurotoxicity and on-target/off-tumor effects. In contrast to T cells, natural killer (NK) cells exhibit a broader source range and can non-specifically lyse tumor cells. Moreover, it can also reduce toxicity and side effects to some extent. This review comprehensively examines recent research progress on CAR-NK therapy for solid tumors, encompassing both in vivo and in vitro studies, with a focus on CAR-NK cell design and production methods. Drawing upon laboratory and clinical evidence, this review summarizes the current challenges and side effects associated with CAR-NK technology.

Chimeric antigen receptor (CAR) therapy represents an innovative form of targeted treatment that employs genetically engineered effector cells to selectively target tumor cells. CAR-T immunotherapy, which uses T cells as effector cells, has demonstrated remarkable efficacy in hematological malignancies. However, its clinical application in solid tumors remains limited due to challenges such as poor tumor infiltration, cytokine release syndrome (CRS), neurotoxicity, off-target effects, and other adverse events. To address these limitations, CAR-engineered natural killer (CAR-NK) cells and macrophages (CAR-M) have been developed. Macrophages, as crucial components of innate and adaptive immunity, exhibit superior tumor microenvironment infiltration and long-term persistence, making them a promising tool for next-generation cancer immunotherapy. This review highlights the construction strategies and preclinical and clinical studies of CAR-M, comprehensively introduces the anti-tumor mechanisms, discusses their advantages and disadvantages compared with other CAR-engineered effector cells, and explores the challenges and prospects for CAR-M in treating solid tumors.

Background Infectious mononucleosis (IM) is an acute self-limited disease caused mainly by Epstein-Barr virus (EBV) that is prone to be missed or misdiagnosed in febrile children due to a lack of obvious clinical symptoms. Establishing a model based on blood cell parameters for identifying patients with IM is important for the subsequent diagnosis and treatment of children with fever. Methods From January to December 2023, data of a total of 5511 febrile children (including 518 IM patients with primary EBV infection) were collected from Children's Hospital Zhejiang University School of Medicine. After assessing the changes in lymphoid clusters on the 3D-DIFF scatter plot and further analyzing the parameters of the scattergrams for quantifying the fluorescence signal changes in IM patients through the probability density function, eleven features were selected from among 41 blood cell parameters to construct the final Novel IM screening model (Novel IMs model). Results The Novel IMs model performed well in three sets, screening IM patients with an accuracy of more than 91.92%. Compared others, the Novel IMs model had the best identification accuracy, specificity, and sensitivity and reached an area under the receiver operating characteristic (ROC) curve (AUC) in identifying IM patients of 0.96. Conclusion This study is the first to develop a machine learning model to screening IM patients from febrile children using parameters obtained from blood cell scattergrams. This convenient and low-cost technique for initial screening of IM by hematology analysis may improve the screening coverage of the disease and further reduce misdiagnosis and underdiagnosis.

Objectives Rotavirus A and human adenovirus are the two most common causes of infantile diarrhea; thus, it is of great importance to find out a rapid and accurate diagnostic method. This study aimed to evaluate the diagnostic significance of latex agglutination test for detection of rotavirus A and human adenovirus. Methods A prospective study was conducted on 214 diarrhea children from September 2018 to March 2019 in our hospital. Fresh stool samples were collected for detection of rotavirus A and human adenovirus by latex agglutination test and quantitative reverse transcription polymerase chain reaction (RT‐qPCR). Then, the consistency of results detected by these two methods was analyzed． Results With performing the latex agglutination test, it was revealed that positive rates for detecting rotavirus A virus and human adenovirus were 23.83% (51/214) and 25.24% (54/214), respectively. Meanwhile, results of RT‐qPCR showed that positive rates for detecting rotavirus A virus and human adenovirus were 58 (27.10%) and 59 (27.57%), respectively. Using RT‐qPCR as the gold standard, the sensitivity and specificity of the latex agglutination test for detecting rotavirus A were 81.03% and 97.44%, and the corresponding values for detecting human adenovirus were 76.27% and 94.19%, respectively. Conclusion This latex agglutination test showed a satisfactory consistency with RT‐qPCR for detecting rotavirus A and human adenovirus. The mentioned commercial assay may be highly appropriate for rapid screening of rotavirus A and human adenovirus.

Objective To investigate the effect of ectopic high expression of OCT4 on the stemness characteristics of bone marrow-derived mesenchymal stromal cells (BM-MSCs). Methods BM-MSCs were collected from three de novo acute lymphoblastic leukemia (ALL) and three aplastic anemia patients (AA), which were cultivated by the whole bone marrow adherent method. Surface markers of BM-MSCs were analyzed by flow cytometry (FCM); meanwhile, growth characteristics were observed with a phase contrast microscope, and population doubling time (PDT) was calculated. The optimal generation cells (P4) were used for the subsequent experiments. Recombinant plasmid pcDNA3.1-OCT4 was constructed and transferred into ALL MSCs by liposome transfection. The cells with stable and high expression of OCT4 were selected by G418 resistance screening and subcloning, of which the expression of OCT4 was verified by FCM, cellular immunofluorescence assay (CIFA), and RT-PCR. The expression of stemness-related transcription factors (TFs) (NANOG, SOX2) and the embryonic stem cell (ESC)-related surface markers (SSEA4, TRA-1-60, and TRA-1-81) were analyzed by FCM, RT-PCR, and CIFA. Embryonic body (EB) formation was performed with the above cells, and triembryonic differentiation marker genes were evaluated by RT-PCR. Results The primary passage of AA MSCs grew more slowly and had longer PDT (16 days on average) than ALL MSCs (10 days on average). AA MSCs presented the same typical morphology and similar expression levels of specific mesenchymal markers as ALL MSCs, whereas the latter had a much better proliferative capacity in P4 cells ( P  < 0.05). Besides, the expression levels of surface markers in ALL MSCs were slightly higher than that in AA MSCs in P4, P7, and P10 cells ( P  < 0.05). Cell lines with stable and high expression of OCT4 were successfully established from ALL MSCs, which were confirmed by CIFA, FCM, and RT-PCR. Compared with untransfected parental MSCs, the mean expression levels of TFs in OCT4 overexpression MSCs were increased from 0.63 ± 0.37% to 39.39 ± 1.85% (NANOG) and from 14.34 ± 2.44% to 91.45 ± 4.56% (SOX2). The average expression levels of ESC surface markers were increased from 3.33 ± 2.35%, 1.59 ± 1.29%, and 1.46 ± 0.86% to 84.98 ± 9.2%, 57.28 ± 6.72%, and 75.88 ± 7.35% respectively for SSEA-4, TRA-1-60, and TRA-1-81, which were confirmed by CIFA analysis. Moreover, the OCT4 overexpression MSCs could form EBs ex vivo and express ectoderm (TUBB3, WNT1), mesoderm (Brachyury, TBX20), and endoderm (SPARC) genes. Conclusion Ectopic high expression of transcription factor OCT4 in BM-MSCs may drive them to grow as ESC-like cells with “stemness” characteristics. Single OCT4 transfection can upregulate the expression of other stemness-related transcription factors such as NANOG and SOX2.

The aims of this study were to investigate the activation of T lymphocytes in peripheral blood from children with Hodgkin's lymphoma (HL) and explore their roles for prognosis in HL. A cohort of 52 newly diagnosed children with HL during the past 10 years was enrolled for analysis in this study. Peripheral blood samples of the patients were acquired before treatment in our hospital, and T-cell subsets were detected by a four-color flow cytometer. CD4+ T cells and CD4+/CD8+ T-cell ratio decreased significantly in patients with HL vs. healthy controls. CD8+ T cells, CD3+CD4+HLA-DR+ T cells, and CD3+CD8+HLA-DR+ T cells increased markedly in patients with HL vs. healthy controls. Receiver-operating characteristic (ROC) curve analysis showed that CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells each distinguished the high-risk group from the low- and intermediate-risk group. The area under the ROC curve for predicting high-risk patients was 0.795 for CD3+CD4+HLA-DR+ T cell and 0.784 for CD3+CD8+HLA-DR+ T cell. A comparison of peripheral blood T-cell subsets that responded differently to therapy showed significantly higher percentages of CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells in patients who achieved complete remission compared to those who did not achieve complete remission. In addition, high percentages of both CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells were associated with inferior event-free survival. Peripheral immune status may be related to disease severity in HL. CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells may be a novel indicator for risk stratification of HL and may be an independent risk factor for inferior outcome in childhood HL.

Messenger ribonucleic acid (mRNA) was discovered in 1961 as an intermediary for transferring genetic information from DNA to ribosomes for protein synthesis. The COVID-19 pandemic brought worldwide attention to mRNA vaccines. The emergency use authorization of two COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, were major achievements in the history of vaccine development. Lipid nanoparticles (LNPs), one of the most superior non-viral delivery vectors available, have made many exciting advances in clinical translation as part of the COVID-19 vaccine and therefore has the potential to accelerate the clinical translation of many gene drugs. In addition, due to these small size, biocompatibility and excellent biodegradability, LNPs can efficiently deliver nucleic acids into cells, which is particularly important for current mRNA therapeutic regimens. LNPs are composed cationic or pH-dependent ionizable lipid bilayer, polyethylene glycol (PEG), phospholipids, and cholesterol, represents an advanced system for the delivery of mRNA vaccines. Furthermore, optimization of these four components constituting the LNPs have demonstrated enhanced vaccine efficacy and diminished adverse effects. The incorporation of biodegradable lipids enhance the biocompatibility of LNPs, thereby improving its potential as an efficacious therapeutic approach for a wide range of challenging and intricate diseases, encompassing infectious diseases, liver disorders, cancer, cardiovascular diseases, cerebrovascular conditions, among others. Consequently, this review aims to furnish the scientific community with the most up-to-date information regarding mRNA vaccines and LNP delivery systems.

With the continuous growth of the global economy, an increasing concern has emerged among individuals with regard to personal digital health. Smart fiber-based sensors meet people’s demands for wearable devices with the advantages of excellent skin-friendliness and breathability, enabling efficient and prompt monitoring of personal digital health signals in daily life. Furthermore, by integrating machine learning and big data analysis techniques, a closed-loop system can be established for personal digital health, covering data collection, data analysis, as well as medical diagnosis and treatment. Herein, we provide a review of the recent research progress on fiber-based wearable sensors for personal digital health. Firstly, a brief introduction is provided to demonstrate the importance of fiber-based wearable sensors in personal digital health. Then, the monitoring of biophysical signals through fiber-based sensors is described, and they are classified based on different sensing principles in biophysical signal monitoring (resistive, capacitive, piezoelectric, triboelectric, magnetoelastic, and thermoelectric). After that, the fiber-based biochemical signal sensors are described through the classification of monitoring targets (biofluids and respiratory gases). Finally, a summary is presented on the application prospects and the prevailing challenges of fiber-based sensors, aiming to implement their future role in constructing personal digital health networks.

The balance between follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr) is crucial for maintaining immune tolerance. Tfh cells are key in producing autoantibodies by providing essential help to germinal center (GC) B cells, while Tfr cells prevent autoimmune inflammatory processes by controling Tfh responses. However, the signals that regulate Tfh and Tfr cells are largely unknown. Due to dysregulated Tfr/Tfh balance and autoantibody production, regulatory B cells (Bregs) have emerged as a key checkpoint in the GC response. Bregs are B cells with immunosuppressive capabilities. Significant advancements have been made in understanding the roles of Bregs, particularly their capacity to produce cytokines with anti-inflammatory properties and regulate Th17, Th1, and regulatory T cells (Tregs) in the context of autoimmune conditions. Bregs also play a pivotal role in shaping the development, regulation, and localization of Tfh and Tfr cells within the immune environment. Consequently, gaining mechanistic knowledge about the interactions between Tfh-Bregs and Tfr-Bregs has the potential to establish homeostasis and suppress the development of autoantibodies in a various disorders. Within the context of autoimmune disorders, this article provides a concise summary of the dysregulation of Tfh/Tfr, highlighting the critical role of Bregs in regulating this balance. The previously unrecognized interplay between Bregs and Tfh/Tfr cells will serve as an essential basis for the comprehension and management of autoimmune illnesses. It also promises to offer invaluable knowledge of the biological mechanisms of autoantibody synthesis.