OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

PURPOSE: To judge the injury mode and injury severity of the real human body through the measured values of anthropomorphic test devices (ATD) injury indices, the mapping relationship of lumbar injury between ATD and human body model (HBM) was explored. METHODS: Through the ATD model and HBM simulation, the mapping relationship of lumbar injury between the 2 subjects was explored. The sled environment consisted of a semi-rigid seat with an adjustable seatback angle and a 3-point seat belt system with a seatback-mounted D-ring. Three seatback recline states of 25°, 45°, and 65° were designed, and the seat pan angle was maintained at 15°. A 23 g, 47 km/h pulse was used. The validity of the finite element model of the sled was verified by the comparison of ATD simulation and test results. ATD model was the test device for human occupant restraint for autonomous vehicles (THOR-AV) dummy model and HBM was the total human model for safety (THUMS) v6.1. The posture of the 2 models was adjusted to adapt to the 3 seat states. The lumbar response of THOR-AV and the mechanical and biomechanical data on L1 - L5 vertebrae of THUMS were output, and the response relationship between THOR-AV and THUMS was descriptive statistically analyzed. RESULTS: Both THOR-AV and THUMS were submarined in the 65° seatback angle case. With the change of seatback angle, the lumbar spine axial compression force (F_z) of THOR-AV and THUMS changed in the similar trend. The maximum F_z ratio of THOR-AV to THUMS at 25° and 45° seatback angle cases were 1.6 and 1.7. The flexion moment (M_y) and the time when the maximum M_y occurred in the 2 subjects were very different. In particular, the form of moment experienced by the L1 - L5 vertebrae of THUMS also changed. The changing trend of M_y measured by THOR-AV over time can reflect the changing trend of maximum stress of L1 and L2 of THUMS. CONCLUSION The F_z of ATD and HBM presents a certain proportional relationship, and there is a mapping relationship between the 2 subjects on F_z. The mapping function can be further clarified by applying more pulses and adopting more seatback angles. It is difficult to map M_y directly because they are very different in ATD and HBM. The M_y of ATD and stress of HBM lumbar showed a similar change trend over time, and there may be a hidden mapping relationship.
Humans ; Lumbar Vertebrae/injuries* ; Finite Element Analysis ; Biomechanical Phenomena ; Manikins ; Spinal Injuries/physiopathology*

Cholesterol on the cell membrane plays a crucial role in regulating membrane proteins,influencing cell functions,and the occurrence and development of tumors.The CD44 receptor protein is closely associated with tumor invasion and metastasis.Therefore,developing biosensors capable of in-situ simultaneous monitoring of cholesterol and CD44 receptor protein on the cell membrane is of great significance for disease diagnosis.In this study,a spatially resolved strategy dual-signal multifunctional electrochemiluminescence(ECL)sensor was designed.The positive potential luminescent probe(ALC)was prepared by combining gold nanostars with luminol and cholesterol oxidase(ChOx),and the negative potential luminescent probe(CZA)was prepared by combining carbon quantum dots(CQD)with ZIF-8 and gold nanoparticles(AuNPs).The dual probes were fixed on dual working electrodes respectively to construct a spatial resolution dual signal sensor,and the signals were independently output with K2S2O8 as co-reactant.When the measurement signal of ALC probe was enhanced due to enzymatic catalysis of cholesterol,CZA synchronously output the internal reference signal,realizing ratio ECL detection of cholesterol,with a linear range of 50 nmol/L-1600 μmol/L and a detection limit of 20 nmol/L.Furthermore,after the double probes were respectively modified with folic acid(FA)and hyaluronic acid(HA),a spatially resolved dual-functional cell sensor was constructed by capturing human hepatoma cells HepG2 through ligand-receptor specific recognition.This sensor enabled the simultaneous monitoring of cholesterol-ChOx catalytic reaction and CD44-HA recognition on the cell membrane,as well as the quantitative detection of cancer cells and cholesterol on the cell membrane.The results showed that the linear detection range for HepG2 cell was 100-10000 cell/mL.By reducing cholesterol on the cell membrane using methyl-β-cyclodextrin(MβCD)downregulated CD44 expression,it was found that the cholesterol content was positively correlated with CD44 expression on the cell membrane.The control experiments showed that the analysis method was feasible.The designed ECL sensor could be used to detect cholesterol ratiometrically and provided a new method for the simultaneous analysis of multiple functional molecules in cells.

Objective:To summarize the clinical features, laboratory findings, treatment and prognosis of children confirmed as Mycoplasma pneumoniae-induced rash and mucositis (MIRM) in children. Methods:This retrospective study concluded 6 children diagnosed as MIRM in Department of Gastroenterology and Infectious Diseases, Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from August 2023 to April 2024. This paper described the characteristics of MIRM and analyzed the therapeutic strategy and prognosis.Results:A total of 6 children were diagnosed as MIRM including 2 boys and 4 girls with an age of onset was 6.4 (3.1, 7.5) years. Among the 6 patients, 4 patients had oral mucosal involvement among whom 2 showed crusting of the lips. Four patients had ocular involvement manifesting as conjunctival congestion and increased secretion. All patients presented with skin lesions, manifesting as target-shaped damage in 4 cases, herpes herpetiformis in 1 case and purpura-like rash in 1 case. Serological tests for Mycoplasma pneumoniae IgM and Mycoplasma pneumoniae nucleic acid test were positive in all 6 cases. Two cases received intravenous immunogloblin infusion combined with methylprednisolone, monotherapy of methylprednisolone in 4 cases. The course of glucocorticoids was 1-7 weeks, and the initial dose was 2-4 mg/(kg·d), which was gradually reduced according to the rash. The children were followed up for 3 to 9 months, no case suffered from long term ocular or cutaneous complications or recurrence of rash. All cases had good prognosis. Conclusions:Children diagnosed as MIRM present with mild symptoms and usually have good prognosis with early identification and appropriate intervention. Individualized therapy should be applied based on the severity of skin involvement.

Objective:To summarize the clinical features, laboratory findings, treatment and prognosis of children confirmed as Mycoplasma pneumoniae-induced rash and mucositis (MIRM) in children. Methods:This retrospective study concluded 6 children diagnosed as MIRM in Department of Gastroenterology and Infectious Diseases, Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from August 2023 to April 2024. This paper described the characteristics of MIRM and analyzed the therapeutic strategy and prognosis.Results:A total of 6 children were diagnosed as MIRM including 2 boys and 4 girls with an age of onset was 6.4 (3.1, 7.5) years. Among the 6 patients, 4 patients had oral mucosal involvement among whom 2 showed crusting of the lips. Four patients had ocular involvement manifesting as conjunctival congestion and increased secretion. All patients presented with skin lesions, manifesting as target-shaped damage in 4 cases, herpes herpetiformis in 1 case and purpura-like rash in 1 case. Serological tests for Mycoplasma pneumoniae IgM and Mycoplasma pneumoniae nucleic acid test were positive in all 6 cases. Two cases received intravenous immunogloblin infusion combined with methylprednisolone, monotherapy of methylprednisolone in 4 cases. The course of glucocorticoids was 1-7 weeks, and the initial dose was 2-4 mg/(kg·d), which was gradually reduced according to the rash. The children were followed up for 3 to 9 months, no case suffered from long term ocular or cutaneous complications or recurrence of rash. All cases had good prognosis. Conclusions:Children diagnosed as MIRM present with mild symptoms and usually have good prognosis with early identification and appropriate intervention. Individualized therapy should be applied based on the severity of skin involvement.

Objective:To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors.Methods:This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels.Results:Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M ( Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) ( OR=1.23, 95% CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced ( OR=0.68, 95% CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95% CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95% CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95% CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95% CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions:Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective To analyze the effect of low-dose methylprednone sodium succinate combined with erythromycin in the treatment of Mycoplasma pneumoniae infection with elevated lactate dehydrogenase(LDH)in children.Methods Children with Mycoplasma pneumoniae pneumonia(MPP)complicated with elevated LDH were divided into control group and treatment group by random number table method.The control group was given erythromycin treatment,and the treatment group was given low-dose methylprednisolone sodium succinate combined with erythromycin treatment.Clinical efficacy and clinical symptom disappearance time were recorded in both groups.Pulmonary X-ray signs,immune function[T cell subsets(CD4+,CD8+,CD4+/CD8+)],immunoglobulin(Ig)A,IgM and serum LDH were compared between the two groups before and after treatment,and the adverse drug reactions of treatment were observed.Results There were 51 cases in control group and 51 cases in treatment group.The total effective rate in treatment group was 96.00％,which was significantly higher than 81.63％in control group(P＜0.05).The fever abatement times in treatment group and control group were(4.22±0.87)and(5.46±0.98)d;cough disappearance times were(6.31±0.98)and(7.49±1.10)d;disappearance times of pulmonary rales were(7.36±1.14)and(8.61±1.23)d,all with significant difference(all P＜0.05).After treatment,the patchy infiltrating shadow sign rates in treatment group and control group were 2.00％and 16.33％;the bronchial wall thickening sign rates were 4.00％and 18.37％,all with significant difference(all P＜0.05).After treatment,IgA levels in treatment group and control group were(0.55±0.11)and(0.68±0.12)g·L-1;IgM levels were(0.90±0.19)and(1.18±0.21)g·L-1;LDH levels were(229.45±10.30)and(240.18±11.17)U·L-1,all with significant difference(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 6.00％and 4.08％respectively,without significant difference(P＞0.05).Conclusion Erythromycin combined with low-dose methylprednone in systemic treatment of children with MPP and elevated LDH has a significant efficacy,and it can promote the reductions of inflammation and immune disorders and accelerate the disease outcomes,and it is safe and reliable.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children, which can be characterized by hyperactivity and(or)impulsivity, inattention, or a combination.The etiology and pathophysiological mechanism of ADHD have not been clarified yet.More and more studies have shown ADHD has intestinal flora disorder, which may affect the occurrence and development of ADHD through microbiome-gut-brain axis (MGBA). Treatment strategies targeting gut microbiota, including probiotics and dietary therapies, are considered to be a novel and effective method for the prevention or treatment of ADHD.This article reviews the changes of intestinal flora and the progress of diet and probiotics in ADHD children, in order to provide new ideas for treatment of ADHD children.

AIM: To explore the characteristics of astigmatism in preschool children before, during and after the COVID-19 epidemic, so as to provide a reference for further prevention and control of children's vision.METHODS: In the consecutive four years from January 2018 to December 2021, a retrospective analysis of vision data was conducted on 2 273 preschool children(4 546 eyes)younger than 4 years old who participated in children's vision screening test in Baiyun district, Guangzhou. They were divided into 1-year old group(ages<1-year old, 420 cases), 2-year old group(1-year ≤ ages <2-year, 543 cases), 3-year old group(2-year ≤ages <3-year, 614 cases), and 4-year old group(3-year ≤ ages<4-year, 696 cases)according to ages. The analysis included astigmatic degrees of children's eyes as well as their conditions of astigmatism.RESULTS: In 2018, the astigmatic degrees of the both eyes of 1-year-old group were higher than those of other groups(P<0.05). The binocular astigmatic degrees of the preschool children in four groups were obviously higher in 2020 than 2019(P<0.05), while they were significantly decreased in 2021 when compared with 2020(P<0.05). From 2019 to 2020, the increase of astigmatic degrees of the right eye is more considerable than the left eye of preschool children in those four groups(P<0.001). Furthermore, the morbidity of astigmatism basically echoes with the changing tendency of astigmatic degrees from 2018 to 2021.CONCLUSIONS: Preschool children in Baiyun district, Guangzhou, have the highest degree of astigmatism and the fastest progression rate within 1 year old. Before COVID-19 epidemic, the changes in astigmatism and prevalence were relatively stable; during COVID-19 epidemic, the astigmatism and prevalence increased significantly and the astigmatic degrees of right eye increased more than that of the left eye; after the normalization of epidemic prevention and control, the astigmatism and prevalence decreased significantly.