Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

The chemical constituents from leaves of Cyclocarya paliurus were isolated and purified by chromatography on silica gel, C_(18) reverse-phase silica gel, and Sephadex LH-20 gel, as well as semi-preparative high-performance liquid chromatography. Six compounds were identified by UV, IR, NMR, MS, calculated ECD, and comparison with literature data as cyclopaloside D(1), boscialin(2),(5R,6S)-6-hydroxy-6-[(E)-3-hydroxybut-1-enyl]-1,1,5-trimethylcyclohexanone(3), 3S,5R-dihydroxy-6R,7-megastigmadien-9-one(4), 3S,5R-dihydroxy-6S,7-megastigmadien-9-one(5), and gingerglycolipid A(6), respectively. Among them, compound 1 was identified as a new tetralone glycoside, and compounds 2-6 were isolated from leaves of C. paliurus for the first time. Furthermore, compound 1 exhibited strong antioxidant activity, with the IC_(50) of(454.20±31.81)μmol·L~(-1) and(881.82±42.31)μmol·L~(-1) in scavenging DPPH and ABTS free radicals, respectively.
Plant Leaves/chemistry* ; Glycosides/isolation & purification* ; Juglandaceae/chemistry* ; Tetralones/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification*

OBJECTIVES: To explore the factors related to prognosis and treatment failure in children with acute lymphoblastic leukemia (ALL). METHODS: A retrospective study was conducted to collect and analyze clinical data of ALL children admitted to the Department of Pediatric Hematology at Tongji Hospital, Huazhong University of Science and Technology, from January 2012 to December 2019, with follow-up until June 2024. RESULTS: A total of 341 children with ALL were included. Among the 69 children with treatment failure, 55 (80%) experienced relapse, while 14 (20%) had non-relapse-related deaths, and no secondary tumors were observed. Initial WBC count ≥50×10⁹/L, positive minimal residual disease, and severe adverse events were identified as independent risk factors for treatment failure (P<0.05). Among the 55 relapsed patients, early relapses were predominant (36%), and the primary site of relapse was the bone marrow (56%). Immunophenotyping (P=0.009), initial WBC count (P=0.011), and fusion genes (P=0.040) were associated with the timing of relapse. High-risk status, T-cell ALL, relapse, and severe adverse events were independent risk factors affecting long-term survival (P<0.05). CONCLUSIONS The prognosis of children with ALL is related to risk stratification, immunophenotyping, relapse status, and occurrence of severe adverse events. Among these factors, relapse is the primary cause of treatment failure. Actively preventing relapse may reduce the treatment failure rate and improve long-term survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Prognosis ; Treatment Failure ; Adolescent ; Infant ; Risk Factors

A retrospective analysis was conducted on the clinical course of two children with PICALM-MLLT10-positive acute leukemia treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between July 2021 and July 2023. The patients were diagnosed with acute T-lymphoblastic leukemia with central nervous system involvement and high-risk acute myeloid leukemia, respectively. Both achieved bone marrow complete remission after conventional chemotherapy combined with venetoclax. Following conversion to molecular negativity, they underwent sequential allogeneic hematopoietic stem cell transplantation. At the latest follow-up, both patients were alive and in good clinical condition. These observations suggest that proceeding to hematopoietic stem cell transplantation after venetoclax-based chemotherapy may improve the long-term survival of children with PICALM-MLLT10-positive leukemia.
Humans ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child, Preschool ; Transplantation, Homologous ; Child ; Leukemia, Myeloid, Acute/genetics* ; Oncogene Proteins, Fusion/genetics*

Pneumococcal vaccine plays a key role in preventing diseases such as pneumonia and meningitis caused by Streptococcus pneumoniae(S.pneumoniae).Capsular polysaccharide,C-polysaccharide and phosphorus content are important indicators for quality control of polysaccharide antigens in vaccine development and production.In this study,a quantitative 1H NMR and 31P NMR method based on a single internal standard hexamethylphosphoramide(HMPA)was developed to achieve simultaneous determination of capsular polysaccharide,C-polysaccharide and phosphorus content in 6A,6B,18C,19A,19F and 23F S.pneumoniae polysaccharide antigens.Using the internal reference comparison method,the effect of solubility of polysaccharide on quantitative 1H NMR determination was investigated.It was found that the determination results of quantitative 1H NMR were affected by the viscosity and concentration of polysaccharide solution.It was found that high viscosity polysaccharides at 3-15 mg/mL and low viscosity polysaccharides at 5-25 mg/mL were the optimal detection solution concentration range.This"one internal standard three quantitative"NMR method has good precision,specificity and accuracy,and provides a valuable new strategy for the quality control of pneumococcal vaccine.

Objective To investigate the effects of microRNA(miR)-30a-regulated MAPK pathway on the formation of intercalation,inflammatory factors and vasoconstriction in a rat model of aortic coarctation.Methods Fifty SD rats were selected to establish the rat model of aortic coarctation,and were randomly divided into control group,model group,miR-NC group,miR-30a group and miR-30a inhibitor group,10 rats in each group.Histopathological changes in the aortic tissue and changes in the elastic fibers and collagen fibers of the aortic mesothelium were observed;The expression of miR-30a,systolic blood pressure before and after the intervention and the expression of serum inflammatory factors in each group were measured by PCR,tail artery manometry and ELISA;Matrix metalloproteinase(MMP)-6,MMP-2 protein expression and MAPK pathway were measured by Western blotting in each group.The expression of MMP-6,MMP-2 and MAPK pathway related proteins were measured by Western blotting.Results The miR-30a inhibitor group improved the degree of vessel wall tearing and disorganized internal arterial wall arrangement;The miR-30a group improved vascular remodeling;miR-30a expression was higher in the model group compared with the control group,and lower in the miR-30a group and miR-30a inhibitor group compared with the miR-NC group,P<0.05;Before the intervention,the difference in systolic blood pressure between the groups compared was not statistically significant,P>0.05;Compared with the control group,systolic blood pressure was higher in the model group,higher expression in the miR-30a group and lower expression in the miR-30a inhibitor group compared with the miR-NC group,P<0.05;compared with the control group,tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-1β expression was higher in the model group,higher expression in the miR-30a group compared with the miR-NC group,lower expression in the miR-30a inhibitor group,P<0.05;higher expression of TNF-α,MMP-6,MMP-2,Ras,Raf,P38 MAPK,ERK1/2 proteins in the model group compared with the control group,higher expression in the miR-30a group compared with the miR-NC group,lower expression in the miR-30a inhibitor group,P<0.05.Conclusion MiR-30a is involved in the process of aortic coarctation formation,inflammatory response,and regulation of aortic coarctation vascular remodeling,possibly through regulation of the MAPK signaling pathway.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To evaluate the quality of test papers and to analyze students'mastery of knowledge through the analysis of test papers,so as to provide reference for the reform of test proposition and correction teaching.Methods:Using paper analysis software(Ver 2.0),the paper quality,the students'scores and the answers to the questions of the final exam paper of Physiology of grade 2021 students majoring in nursing were analyzed.Results:The composition of the test paper was consistent with the requirements of the teaching programme,the difficulty of subjective and objective test questions was moderate,the differentiation of subjective test questions was good,the differentiation of objective test questions was general,and the reliability and validity were good.The overall performance was basically normal distribution.The full score ratio of objective test questions was higher than that of subjective test questions,and the zero score test questions were mostly concentrated in chapter 10 and chapter 4.Conclusion:Test paper analysis can feedback the problems and shortcomings of test paper proposition and teaching process,promote the quality of test paper and teaching model innovation,and improve the quality of teaching.

Objective To study and compare the oral microbiota and metabolites of children with Henoch Schonlein purpura(HSP)to identify specific microbiota and metabolites related to this disease and elucidate the pathogenesis of HSP.Methods Three groups of qualified subjects were included,including 20 in the HSP group,20 in the HSP nephritis(HSPN)group,and 20 in the control group.Perform high-throughput 16S rRNA sequencing and metabolic profiling of saliva from each group to analyze the correlation between differential microbiota and differ-ential metabolites.Results(1)Compared with the control group,there was a significant difference in richness and diversity in the HSPN group(P＜0.05).At the same time,there was no significant difference in richness and diver-sity in the HSP group(P＞0.05).Compared with the HSP group,the abundance,and diversity of the HSPN group were significantly increased(P＜0.05).At the genus level,the proportion of Streptococcus in each group is the high-est.Compared with the control group,there was no significant correlation between the HSP group and the genus of bacteria.In contrast,the HSPN group showed a significant increase in the genera of Pseudomonas and Parabacteroi-des(P＜0.05).Compared with the HSP group,the abundance of Pseudomonas and Parabacteroides in the HSPN group was significantly increased(P＜0.05).(2)Compared with the control group,the HSPN group had 12 differen-tial metabolites involving nine metabolic pathways,such as phenylalanine metabolism;There was no significant dif-ference in metabolites and no metabolic pathway in the HSP group.Compared with the HSP group,the HSPN group has 15 differential metabolites involving nine metabolic pathways,such as phenylalanine metabolism.(3)In the HSPN and control groups,Pseudomonas and Parabacteroides negatively correlated with Phenylalanine metabolic pathway products.In the HSPN and HSP groups,Pseudomonas,Parabacteroides,and Phenylalanine metabolic path-way products were negatively correlated.The metabolites involved in phenylalanine metabolism in the oral cavity are 2-hydroxycinnamic acid,Phenylpyruvic acid,and N-acetyl-L-phenylalanine.Conclusion There is a significant dif-ference between HSPN and HSP children and healthy children.Streptococcus,Pseudomonas,and Parabacteroides may be one of the trigger factors of HSPN,and Phenylalanine metabolism may be one of the pathways in the patho-genesis of HSPN.Children with HSPN have a more pronounced imbalance in oral microbiota and greater differences in metabolic products than children with HSP.