Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.

Objective To investigate the relationship between disease courses and severity and monocyte subsets distribution and surface CD31 intensity in patients of hemorrhagic fever with renal syndrome (HFRS). Methods Peripheral blood samples from 29 HFRS patients and 13 normal controls were collected. The dynamic changes of classical monocyte subsets (CD14⁺⁺CD16^-), intermediated monocyte subsets (CD14⁺⁺CD16⁺) and non-classical monocyte subsets (CD14⁺CD16⁺⁺) and the mean fluorescent intensity (MFI) of CD31 on monocyte subsets were detected by multiple-immunofluorescent staining and flow cytometry. Results In acute phase of HFRS, the ratio of classical monocyte subsets to total monocytes was dramatically decreased compared to convalescent phase and normal control. It was still much lower in convalescent phase compared to normal controls. The ratio of classical monocyte subsets to total monocytes were decreased in HFRS patients compared to that in normal control, whereas there was no difference between severe/critical groups and mild/moderate groups. On the contrary, the ratio of intermediate monocyte subsets to total monocytes in acute phase of HFRS was significantly increased compared to convalescent phase and normal control. The ratio of intermediate monocyte subsets to total monocytes were increased in HFRS patients compared to that in normal control, whereas no difference was found between severe/critical groups and mild/moderate groups. Phases or severity groups had no difference in ratio of non-classical monocyte subsets to total monocytes. Additionally, the ratio of classical monocyte subsets had a tendency to decline and that of intermediate monocyte subsets showed an increase both to total monocytes between the acute and convalescent phases in 11 HFRS patients with paired-samples. Moreover, in acute phase of HFRS, the mean fluorescent intensity (MFI) of CD31 on three monocyte subsets all decreased, specifically classical monocyte subsets showed the highest MFI of CD31 while the normal control reported the highest MFI of CD31 in non-classical monocyte subsets. In convalescent phase, the MFI of CD31 on classical and intermediated monocyte subsets were both lower than that of normal control, while MFI of CD31 was still significantly lower than normal control on non-classical monocyte subsets. Finally, MFI of CD31 on classical and intermediated monocyte subsets in severe/critical group were both lower than those in mild/moderate group, showing no statistical difference in MFI of CD31 on non-classical monocyte subset across groups of different disease severity. Conclusion The ratio of classical and intermediated monocyte subsets to total monocytes are correlated with the course of HFRS, and so are the surface intensity of CD31 on these monocyte subsets with the disease course and severity. The surface intensity of CD31 on non-classical monocyte subsets, however, is correlated only with the course of the disease. Together, the underlying mechanisms for the observed changes in monocyte subsets in HFRS patients should be further investigated.
Humans ; Monocytes ; Lipopolysaccharide Receptors ; Hemorrhagic Fever with Renal Syndrome ; Receptors, IgG ; Disease Progression

The concept of "ntigen"is a relative one. The narrow concept of it condenses the process of activation of adaptive immune response and re-recognition of the same antigen, revealing the protective mechanism of vaccines with great significance for research and development of vaccines. However, the narrow concept involves adaptive immune system members: B cells, T cells and their effector products, which is difficult for beginners to understand the inherent meaning. Meanwhile, antigen classification fully summarizes the immune response process, so a variety of classification approach increases the difficulty in learning. Our teaching team analyzes the difficulties of this chapter in depth, and we implements the strategy that takes antibody structure and function as the breakthrough point and simplified adaptive immune response process as the core in teaching. A mind map that includes the main contents of this chapter is made during the process, which promotes the effectiveness of classroom teaching greatly.
Learning ; Vaccines ; Antibodies

Group 2 innate lymphoid cells (ILC2s) are novel innate immune cells. Similar to T cells, ILC2s can secrete Th2 cytokines and initiate and maintain type 2 immune responses, which are also named as cross-border immune cells between innate immunity and adaptive immunity. In recent years, infectious diseases caused by pathogenic viruses have become a global healthcare challenge with the outbreaks of Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS) and novel coronavirus disease 2019 (COVID-19). As a member of the innate lymphocyte family, ILC2s are involved in the development of group 2 inflammatory diseases and can activate immune activity, playing an essential role in the repair of tissue damage and in the body’s defense, which also can participate in the immune response and play an important role in viral immunity when a virus attacks on the body. This study reviews the defensive role of ILC2s in viral infections, providing a theoretical basis for elaborating the role of ILC2s in viral infectious diseases.

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research.

Although hyaluronic acid (HA) has been developed as a nanoparticle (NP; 320–400 nm) for a drug delivery system, the tissue targeting efficacy and the pharmacokinetics of HA-NPs are not yet fully understood. After a dose of 5 mg/kg of cyanine 5.5-labeled HA-NPs or HA-polymers was intravenously administrated into mice, the fluorescence was measured from 0.5 h to 28 days. The HA-NPs fluorescence was generally stronger than that of HA-polymers, which was maintained at a high level over 7 days in vivo, after which it gradually decreased. Upon ex vivo imaging, liver, spleen, kidney, lung, testis and sublingual gland fluorescences were much higher than that of other organs. The fluorescence of HA-NPs in the liver, spleen and kidney was highest at 30 min, where it was generally maintained until 4 h, while it drastically decreased at 1 day. However, the fluorescence in the liver and spleen increased sharply at 7 days relative to 3 days, then decreased drastically at 14 days. Conversely, the fluorescence of HA-polymers in the lymph node was higher than that of HA-NPs. The results presented herein may have important clinical implications regarding the safety of as self-assembled HA-NPs, which can be widely used in biomedical applications.
Animals ; Drug Delivery Systems ; Fluorescence ; Hyaluronic Acid ; Kidney ; Liver ; Lung ; Lymph Nodes ; Mice ; Nanoparticles ; Pharmacokinetics ; Spleen ; Sublingual Gland ; Testis ; Tissue Distribution ; Toxicokinetics

Objective To develop clinical practice guidelines for breastfeeding in neonates in hospital conforming to the situation in China by adaptation of existing guidelines.Methods According to ADAPTE methodology and current status of breastfeeding in neonates in hospital,we searched existing guidelines and systematic reviews of breastfeeding,used AGREE Ⅱ to evaluate the guidelines,content analysis method was used to select and integrate the content of the evidence,and feasibility investigation and expert external review were performed for the established guidelines.Results A total of 10 guidelines,3 evidence summaries and 4 systematic reviews were included,and the "Evidence-Based Guideline:Breastfeeding of Neonates in the Hospital" were established,involving 8 aspects:breastfeeding promotion,screening,expression,storage,transport,reception,procedures and quality management,and a total of 83 evidences were recommended,which were practical and recommended by all experts.Conclusion High quality evidence resources provided by the established clinical practice guideline can provide reliable evidence support for clinical practice.

Although hyaluronic acid (HA) has been developed as a nanoparticle (NP; 320–400 nm) for a drug delivery system, the tissue targeting efficacy and the pharmacokinetics of HA-NPs are not yet fully understood. After a dose of 5 mg/kg of cyanine 5.5-labeled HA-NPs or HA-polymers was intravenously administrated into mice, the fluorescence was measured from 0.5 h to 28 days. The HA-NPs fluorescence was generally stronger than that of HA-polymers, which was maintained at a high level over 7 days in vivo, after which it gradually decreased. Upon ex vivo imaging, liver, spleen, kidney, lung, testis and sublingual gland fluorescences were much higher than that of other organs. The fluorescence of HA-NPs in the liver, spleen and kidney was highest at 30 min, where it was generally maintained until 4 h, while it drastically decreased at 1 day. However, the fluorescence in the liver and spleen increased sharply at 7 days relative to 3 days, then decreased drastically at 14 days. Conversely, the fluorescence of HA-polymers in the lymph node was higher than that of HA-NPs. The results presented herein may have important clinical implications regarding the safety of as self-assembled HA-NPs, which can be widely used in biomedical applications.

Temporal and subcellular distributions of hyaluronic acid (HA) as a degradable nanoparticle (NP) in animals were investigated to determine if HA-NP could be utilized as an appropriate drug delivery system. After mice were intravenously injected with 5 mg/kg of Cy5.5-labeled HA-NP sized 350–400 nm or larger HA-polymers, the fluorescence intensity was measured in all homogenized organs from 0.5 h to 28 days. HA-NP was greatly detected in spleen, liver and kidney until day 28, while it was maintained at low levels in other organs. HA-polymer was observed at low levels in all organs. HA-NP quantities in spleen and liver were reduced until day 3, but increased sharply between days 3 and 7, then decreased again, while their HA-polymers were maintained at low levels until day 28. In kidneys, both HA-NP and HA-polymer showed high levels after 0.5 h of administration, but steadily decreased until day 28. According to ultrastructural analyses, HA-NP was engulfed in Kupffer cells of liver and macrophages of spleen and kidney at day 1 and was accumulated in the cytoplasm of kidney tubular cells at day 7. Overall, these findings suggest that HA-NP could be considered a desirable drug carrier in the liver, kidney, or spleen.
Animals ; Cytoplasm ; Drug Carriers* ; Drug Delivery Systems ; Fluorescence ; Hyaluronic Acid* ; Kidney ; Kupffer Cells ; Liver ; Macrophages ; Mice* ; Nanoparticles* ; Pharmacokinetics ; Spleen

Hyaluronic acid (HA) has been investigated for biomedical and pharmaceutical applications. This study was conducted to determine the distributions of HA nanoparticles (NPs; size 350–400 nm) and larger HA polymers in mice at intervals after application. ¹⁷⁷Lutetium (Lu)-labeled HA-NPs or HA polymers were intravenously injected (5 mg/kg) into male ICR mice, and radioactivity levels in blood and target organs were measured from 0.25 h to 28 days post-injection. In blood, the radioactivities of HA-NPs and HA polymer peaked at 0.5 h after injection but were remarkably decreased at 2 h; subsequently, they maintained a constant level until 6 days post-injection. HA-NPs and HA polymers were observed in the liver, spleen, lung, kidney, and heart (in ascending order) but were seldom observed in other organs. After 3 days, both the HA-NP and HA polymer levels showed similar steady decreases in lung, kidney, and heart. However, in liver and spleen, the HA-NP levels tended to decrease gradually after 1 day and both were very low after 14 days, whereas the HA polymer level accumulated for 28 days. The results indicate that HA-NPs, with their faster clearance pattern, may act as a better drug delivery system than HA polymers, especially in the liver and spleen.
Animals ; Drug Delivery Systems ; Heart ; Humans ; Hyaluronic Acid* ; Kidney ; Liver ; Lung ; Male ; Mice* ; Mice, Inbred ICR ; Nanoparticles* ; Polymers* ; Radioactivity ; Spleen