Objective:To analyze the changes in the phylogenetic and antigenic characteristics of the hemagglutinin (HA) gene of influenza virus A(H3N2) [A(H3N2)] during the 2022-2024 influenza seasons in Beijing.Methods:The data of influenza-like cases and A(H3N2) strains from 17 network laboratories and their corresponding sentinel hospitals were collected during the 2022-2024 influenza seasons. The HA genes were amplified and sequenced after extracting nucleic acids of the chosen virus strains. BioEdit, the nucleotide and amino acid sequence identity were conducted, and the maximum likelihood method in MEGA 5.0 software was used to construct the phylogenetic tree of HA genes. Web Logo displayed the amino acid mutation, and the N-glycosylation sites of HA online were analyzed using the NetNGlyc1.0 Server online. The Datamonkey platform was utilized to analyze the positive selection pressure sites of the HA protein.Results:The 2022-2024 influenza season includes 2022-2023 and 2023-2024. During the influenza seasons of 2022-2024, the positive rates of A(H3N2) nucleic acid were 10.35% (2 127/20 543) and 10.47% (4 386/41 876), respectively. In the 2022-2023 influenza season, there were two peaks in the A(H3N2). The comparison of HA genes between all A(H3N2) strains studied with the 2022-2024 vaccine strain (A/Darwin/9/2021) revealed that all of the strains studied have the two amino acid mutations involving 186 and 225 receptor binding sites. There were 31 amino acid substitutions in the 2022-2023 influenza season, of which 18 variant sites involved antigenic determinants. There were 35 amino acid mutations during the 2023-2024 influenza season, of which 14 were related to antigenic determinants. There were changes in the genetic evolutionary subclades of A(H3N2) strains in two influenza seasons: from 2022 to 2023, three evolutionary subclades were co-prevalent together, with the 3C.2a1b.2a.2a.3a.1 accounting for 76.67% (23/30), the 3C.2a1b.2a.1a accounting for 20.00% (6/30), the 3C.2a1b.2a.2a.1 accounting for 3.33% (1/30); from 2023 to 2024, two subclades were prevalent, with 3C.2a1b.2a.2a.3a.1 accounting for 95.12% (39/41) and 3C.2a1b.2a.2a.1 accounting for 4.88% (2/41). The glycosylation site changes of the HA protein of A(H3N2) have been enhanced from 2023 to 2024. The 145 amino acid position of the HA protein of the A(H3N2) was the positive selection site for stress selection site analysis.Conclusions:The evolutionary subclades of the HA gene of A(H3N2) in Beijing showed changes from 2022 to 2024, and the glycosylation site polymorphism of the HA protein of A(H3N2) significantly increased from 2023 to 2024. Continuous monitoring of HA mutations in the A(H3N2) is crucial, providing a basis for developing influenza prevention and control strategies, as well as new strategic support for screening influenza vaccine components, vaccine design, and discovery of drug targets.

Objective:To analyze the changes in the phylogenetic and antigenic characteristics of the hemagglutinin (HA) gene of influenza virus A(H3N2) [A(H3N2)] during the 2022-2024 influenza seasons in Beijing.Methods:The data of influenza-like cases and A(H3N2) strains from 17 network laboratories and their corresponding sentinel hospitals were collected during the 2022-2024 influenza seasons. The HA genes were amplified and sequenced after extracting nucleic acids of the chosen virus strains. BioEdit, the nucleotide and amino acid sequence identity were conducted, and the maximum likelihood method in MEGA 5.0 software was used to construct the phylogenetic tree of HA genes. Web Logo displayed the amino acid mutation, and the N-glycosylation sites of HA online were analyzed using the NetNGlyc1.0 Server online. The Datamonkey platform was utilized to analyze the positive selection pressure sites of the HA protein.Results:The 2022-2024 influenza season includes 2022-2023 and 2023-2024. During the influenza seasons of 2022-2024, the positive rates of A(H3N2) nucleic acid were 10.35% (2 127/20 543) and 10.47% (4 386/41 876), respectively. In the 2022-2023 influenza season, there were two peaks in the A(H3N2). The comparison of HA genes between all A(H3N2) strains studied with the 2022-2024 vaccine strain (A/Darwin/9/2021) revealed that all of the strains studied have the two amino acid mutations involving 186 and 225 receptor binding sites. There were 31 amino acid substitutions in the 2022-2023 influenza season, of which 18 variant sites involved antigenic determinants. There were 35 amino acid mutations during the 2023-2024 influenza season, of which 14 were related to antigenic determinants. There were changes in the genetic evolutionary subclades of A(H3N2) strains in two influenza seasons: from 2022 to 2023, three evolutionary subclades were co-prevalent together, with the 3C.2a1b.2a.2a.3a.1 accounting for 76.67% (23/30), the 3C.2a1b.2a.1a accounting for 20.00% (6/30), the 3C.2a1b.2a.2a.1 accounting for 3.33% (1/30); from 2023 to 2024, two subclades were prevalent, with 3C.2a1b.2a.2a.3a.1 accounting for 95.12% (39/41) and 3C.2a1b.2a.2a.1 accounting for 4.88% (2/41). The glycosylation site changes of the HA protein of A(H3N2) have been enhanced from 2023 to 2024. The 145 amino acid position of the HA protein of the A(H3N2) was the positive selection site for stress selection site analysis.Conclusions:The evolutionary subclades of the HA gene of A(H3N2) in Beijing showed changes from 2022 to 2024, and the glycosylation site polymorphism of the HA protein of A(H3N2) significantly increased from 2023 to 2024. Continuous monitoring of HA mutations in the A(H3N2) is crucial, providing a basis for developing influenza prevention and control strategies, as well as new strategic support for screening influenza vaccine components, vaccine design, and discovery of drug targets.

Objective To propose specific suggestions for exemption management of X-ray devices applying for exemption management. Methods The weight analysis of influence of shielding thickness and tube voltage on the radiation dose leakage of low-energy X-ray devices was carried out through test analysis, and the radiation status of 50 X-ray devices applied for end-user exemption in Shenzhen, China was investigated. Results There was no significant correlation between the ambient dose equivalent rate and the tube voltage and tube current of the X-ray device. The ambient dose equivalent rate of 50 X-ray devices was 0.16-1.20 μSv/h. Among them, 8 X-ray devices had radiation dose leakage, that is, the ambient dose equivalent rate was greater than 0.36 μSv/h; the ambient dose equivalent rate of one X-ray device was 1.2 μSv/h, exceeding exemption management requirements. Conclusion Applications for exemption management and filing of X-ray devices should be treated differently, and their own shielding effect and inherent safety have a greater impact on radiation safety, which should be focused on.

With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids (tFNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, tFNAs have been widely applied in the biomedical field as three-dimensional DNA nanomaterials. Surprisingly, tFNAs exhibit positive effects on cellular biological behaviors and tissue regeneration, which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity, tFNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization, intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic tFNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic tFNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone, cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.
Nucleic Acids/chemistry* ; Regenerative Medicine ; Consensus ; Reproducibility of Results ; DNA/chemistry*

Objective:To explore the safety and advantages of non-cryopreserved sibling umbilical cord blood hematopoietic stem cell transplantation for major thalassaemia in children.Methods:From October 2016 to June 2021, 9 patients with major beta thalassaemia received non-cryopreserved hematopoietic stem cell transplantation of sibling umbilical cord blood at Zhongshan Hospital of Xiamen University. The pretreatment scheme, the process of stem cell implantation and follow-up were analyzed and summarized.Results:Among the 9 cases, there were 5 males and 4 females with a median age of 4(2~11)years. Median level of ferritin was 2 997(1 936~5 512)μg/L. At gestational weeks 12~16, each patient's mother underwent villi testing to confirm that the donor without thalassaemia major was complete HLA-matched with the patient. All of them received an intensive conditioning regimen made up of cyclophosphamide(CTX), fludarabine and busulfan(Bu). Graft-versus-host disease(GVHD) was prevented by cyclosporine A(CSA)and mycophenolate mofetil(MMF)with or without methotrexate(MTX). Except for one failed implant, 8 cases were successfully engrafted. Median time of neutrophil implantation was 19.5(15~26)days, median time of platelet implantation 32(22~34)days and median time of erythrocyte implantation 30.5(18~37)days. Up until September 1, 2021, the median follow-up period was 27(3~59)months and the rate of successful engraftment 88.89%. There was no transplant-related mortality. Overall survival was 100% and thalassaemia-free survival 88.89%. Two patients developed grades Ⅱ skin acute GVHD(22.2%). No grade Ⅲ-Ⅳ GVHD or chronic GVHD occurred. Epstein-Barr virus infection occurred in 1 case.No infection of cytomegalovirus occurred.Conclusions:For major thalassaemia in children, stem cell transplantation of non-cryopreserved sibling cord blood is both safe and feasible with a high implantation rate and a low incidence of GVHD.

Objective To observe the efficacy and safety of reduced-intensity conditioning regimen used in allogeneic hematopoietic stem cell transplantation (HSCT) for children with β-thalassemia major.Methods We retrospectively analyzed the clinical data of 15 children with β-thalassemia major undergoing allogeneic HSCT with a reduced-intensity conditioning regimen from March 2013 to March 2017.Fifteen patients were diagnosed definitely,and the median age at transplantation was 5 years (range:3-6 years),including 11 with HSCT from unrelated donors (UDs),3 of HLA 8/10 matched and 8 of HLA10/10 matched.The remaining 4 patients out of 15 with HSCT were from related donors with HLA matched,3 donors were siblings and 1 was mother.All patients used a reduced-intensity conditioning regimen.The median mononuclear cell (MNC) dose and CD34 positive cell dose were 11.4 × 108/kg (range:4.8-20 × 108/kg)and 9.8 × 106/kg (range:5.9-27.2 × 106/kg),respectively.Graft-versus-host disease (GVHD) was prevented by cyclosporine A,methotrexate,MMF and ATGf.Results All 15 patients had successful engraftment.Median time to neutrophil and platelet engraftment was 12 days (range:9-21 days) and 15 days (range:10-25 days) respectively.Two patients developed grades Ⅱ acute GVHD and 4 patients developed chronic GVHD from unrelated donors,while there was no acute GVHD and 1 patient developed chronic GVHD from related donors.No patients suffered from serious transplantation-related complications,such as hepatic veno-occlusive disease (VOD),hemorrhagic cystitis,EB virus reactivation,CMV reactivation and hepatitis C,etc.The median follow-up time was 24 months (range:2-48 months).All patients were healthy and became transfusion-independent.Conclusion The reduced-intensity conditioning regimen proved to be safe and effective for children with β-thalassemia major given allogeneic HSCT.

OBJECTIVETo understand the infection status of enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) among children receiving health examination for child care setting entrance in Beijing and their related medical care seeking practice and provide evidence for the estimation of disease burden caused by hand foot and mouth disease (HFMD).

METHODSSerological survey was conducted in the local children receiving health examination for child care setting entrance. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect anti-EV71 and anti-Cox A16 IgG and IgM.

RESULTSA total of 813 children were surveyed (mean age: 3.5 ± 1.0 year old). The seropositive rate was 61.9% and 4.4% for anti-Cox A16 IgG and IgM. The seropositive rate was 9.3% and 1.1% for anti-EV71 IgG and IgM. No significant difference was observed in sex specific seropositive rate (P > 0.05). However, significant differences were found in seropositive rate among different age groups (P < 0.05). Among the children who were anti-Cox A16 positive, 7.8% had ever had rashes on their hands and feet, mouth or buttocks (HFMD-like rashes). Among the children who were anti-EV71 positive, 10.7% had ever had HFMD-like rashes. For the children who were anti-Cox A16 or anti-EV71 positive, only 7.1% were brought to see doctors by their parents. However, among the seropositive children with rashes, 80.5% were brought to see doctors.

CONCLUSIONIn the healthy children at the age to go to child care setting in Beijing, most had ever infected with Cox A16. The anti-EV71 positive rate was much lower than the anti-Cox A16 positive rate. It was necessary to strengthen the prevention and control of EV71 infection in child cares settings.

Antibodies, Anti-Idiotypic ; blood ; Beijing ; epidemiology ; Child Health Services ; utilization ; Child, Preschool ; Cost of Illness ; Enterovirus A, Human ; isolation & purification ; Enzyme-Linked Immunosorbent Assay ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Male ; Parents ; psychology ; Patient Acceptance of Health Care ; statistics & numerical data

Objective To understand the infection status of enterovirus 71(EV71) and coxsackievirus A16(Cox A16) among children receiving health examination for child care setting entrance in Beijing and their related medical care seeking practice and provide evidence for the estimation of disease burden caused by hand foot and mouth disease(HFMD). Methods Serological survey was conducted in the local children receiving health examination for child care setting entrance. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect anti-EV71 and anti-Cox A16 IgG and IgM. Results A total of 813 children were surveyed(mean age:3.5±1.0 year old). The seropositive rate was 61.9%and 4.4%for anti-Cox A16 IgG and IgM. The seropositive rate was 9.3% and 1.1% for anti-EV71 IgG and IgM. No significant difference was observed in sex specific seropositive rate (P>0.05). However,significant differences were found in seropositive rate among different age groups(P<0.05). Among the children who were anti-Cox A16 positive, 7.8%had ever had rashes on their hands and feet,mouth or buttocks(HFMD-like rashes). Among the children who were anti-EV71 positive,10.7%had ever had HFMD-like rashes. For the children who were anti-Cox A16 or anti-EV71 positive,only 7.1% were brought to see doctors by their parents. However,among the seropositive children with rashes,80.5% were brought to see doctors. Conclusion In the healthy children at the age to go to child care setting in Beijing,most had ever infected with Cox A16. The anti-EV71 positive rate was much lower than the anti-Cox A16 positive rate. It was necessary to strengthen the prevention and control of EV71 infection in child cares settings.

BACKGROUND:The main therapy of severe aplastic anemia in children is immunosuppressive therapy or stem celltransplantation, but the latter one is restricted due to few donor sources. Haploidentical hematopoietic stem celltransplantation is commonly used in leukemia, but it is stil rarely reported in the treatment of aplastic anemia. OBJECTIVE:To investigate the effect of haploidentical hematopoietic stem celltransplantation combined with placenta-derived mesenchymal stem celltransplantation for children with severe aplastic anemia. METHODS:A 7-year-old girl who had been confirmed as having severe aplastic anemia for 1.5 years received a cotransplantation of haploidentical hematopoietic stem cells combined with placenta-derived mesenchymal stem cells on July 9th , 2012. The donor was her mother. The preconditioning regimen consisted of fludarabine, cyclophosphamide, and anti-thymocyte globulin. RESULTS AND CONCLUSION:Time of neutrophil recovery (>0.5×10 9/L) was+9 days, and hematopoietic reconstruction was complete at+12 days. The short tandem repeat analysis showed 100%donor’s genotype at+100 days. Immunosuppressive drugs were stopped at+8 months, and no acute or chronic graft-versus-host disease occurred. With a fol ow-up of 18 months, she was in the disease-free survival period. Our findings suggest that the cotransplantation of al ogeneic haploidentical hematopoietic stem cells and placenta-derived mesenchymal stem cells is a new effective approach for children with severe aplastic anemia, which is worth exploring in the future.

To establish vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) as secretary biomarkers for cell growth on topographic substrates, we have evaluated the secretion and expression of these 2 factors by SH-SY5Y human neuroblastoma cells on poly-L-lactide (PLLA) micropillar arrayed topographic substrates. We fabricated topographic substrates with UV lithography, silicon etching and polydimethylsiloxane-based replica molding, and interfaced SH-SY5Y human neuroblastoma cells with both the topographic substrates and PLLA flat substrates. Cell morphology and spreading were examined with scanning electron microscopy. The secretion and mRNA expression of VEGF and IL-8 were evaluated with enzyme linked immunosorbent assay (ELISA) and real time qPCR, respectively, 24 hours after cell plating. We successfully achieved 4 topographic substrates with a nominal pillar diameter of 2 microm and 4 microm, and a nominal pillar spacing of 2 microm and 7 microm. We found that the secretion and mRNA expression of VEGF and/or IL-8 by SH-SY5Y cells on 2-2 microm (pillar diameter-spacing), 4-2 microm and 4-7 microm topographic substrates were upregulated in comparison to those by cells on PLLA flat substrate, 24 hours after cell plating. Furthermore, both cytokines were even more substantially upregulated on the 2-7 microm substrate than on the other 3 topographic substrates. Compared to those on PLLA flat substrate, cells on topographic substrates showed significant changes in morphology (spreading area, perimeter and roundness), and the increase in the secretion and mRNA expression of VEGF and IL-8 was accompanied with a decrease in cell spreading areas. These results provided evidence that pillar arrayed topography was an important microenvironmental factor in affecting VEGF and IL-8 expression or secretion, and VEGF and IL-8 might serve as important secretary biomarkers for growth on topographic substrates by SH-SY5Y cells.
Biomarkers ; Cell Line ; Cell Proliferation ; Cellular Microenvironment ; Humans ; Interleukin-8 ; genetics ; secretion ; Neuroblastoma ; secretion ; Polyesters ; chemistry ; RNA, Messenger ; genetics ; Vascular Endothelial Growth Factor A ; genetics ; secretion