The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

Background: Intradermal microdroplet injections of botulinum toxin type-A (BoNT/A) effectively ameliorate rosacea-related angiogenesis, but the mechanism remains unclear. Objective: To explore the anti-angiogenesis of BoNT/A in the rosacea-like mouse model and to measure the secretion of vascular endothelial growth factor (VEGF) by mast cells. Methods: A rosacea-like mouse model was induced by LL37 in both Mas-related G-proteincoupled receptor B2 conditional knockout (MrgprB2 −/− ) mice and wild-type (WT) mice, then treated with BoNT/A and/or Apatinib. The abundance of endothelial cells and mast cells in mouse skin was determined using dual immunofluorescence staining. The VEGF levels in supernatants and cell lysates of laboratory of allergic disease 2 (LAD2) mast cells were assessed using reverse transcription quantitative polymerase chain reaction, western blots, and enzyme-linked immunosorbent assay. The effect of conditioned medium (CM) collected from LAD2 on human umbilical vein endothelial cells (HUVECs) was determined using tube formation assays. The number of proliferative cells was confirmed using the 5-ethynyl-2’-deoxyuridine incorporation assays.The effect of BoNT/A on the internalization of Mas-related G-protein-coupled receptor X2 (MRGPRX2) was detected using flow cytometry and immunofluorescence staining. Results: LL37-induced rosacea-like skin manifestations were significantly alleviated in MrgprB2 −/− mice compared to WT controls. BoNT/A mitigated the LL37-induced secretion of VEGF by LAD2. The CM from BoNT/A-treated LAD2 inhibited HUVEC proliferation and tube formation. The LAD2 cells co-treated with LL37 and BoNT/A exhibited dramatically enhanced MRGPRX2 internalization. Conclusion BoNT/A enhances LL37-mediated MRGPRX2 internalization in mast cells, thereby reducing VEGF secretion and neovascularization and improving facial flushing symptom in rosacea.

Objective To observe the effects of 3 different nutritional support modes of nasogastric tube nutrition,nasoenteric tube nutrition and nasoenteric tube combined with nasogastric tube nutrition on the biliary-related indices of critically ill patients.Methods The observational research method was conducted,the patients admitted to the department of intensive care unit(ICU)of Qingdao Hospital,University of Health and Rehabilitation Sciences(Qingdao Municipal Hospital)from June 2023 to May 2024 serving as the subjects of the study.The subjects were divided into three groups,namely the nasogastric tube group(indwelling nasogastric tube for enteral nutrition),the nasoenteric tube group(indwelling nasoenteric tube for enteral nutrition),and the mixed nutrition group(indwelling nasoenteric tube combined with naso-gastric tube for enteral nutrition)according to the different modes of enteral nutrition given.The clinical data of the patients was collected,including gender,age,previous underlying diseases,nutritional risk screening 2002(NRS2002)score,acute physiology and chronic health evaluationⅡ(APACHEⅡ),gallbladder volume,data on laboratory-related indices,and prognosis during hospitalisation.Compare the differences between the observed indicators and their change values before and after the initiation of enteral nutrition within each group;analyse the correlation between gallbladder volume and other observed indicators using Spearman's correlation analysis;screen the influencing factors of gallbladder volume using univariate regression analysis;screen the influencing factors of ICU patients'survival during hospitalisation using multifactorial Logistic regression analysis,and plot the receiver operator characteristic curve(ROC curve)of the subjects to analyse the predictive value of each influencing factor on patients'prognosis.Results A total of 141 patients who met the inclusion criteria were included in the study,comprising 54 cases in the nasogastric tube group,38 cases in the nasoenteric tube group,and 49 cases in the mixed nutrition group.Of the patients who survived during ICU hospitalization,105 survived,while 36 died,mortality was 25.53%.① No statistically significant differences were observed in the comparison of gender,age,previous underlying disease,NRS2002 score,and APACHEⅡscore among the enrolled groups.② A comparative analysis was conducted on the biliary-related indexes of the nasogastric tube and nasoenteric tube groups before and after the initiation of enteral nutrition.The results revealed no statistically significant differences between the two groups.On the 7th day of enteral nutrition initiation,the gallbladder volume of the nasoenteric tube group was found to be significantly larger than the gallbladder volume on the 1st day(cm3:28.00±6.36 vs.25.20±4.75,P<0.05).In the mixed nutrition group,the gallbladder volume on the initiation of enteral nutrition on day 7 was significantly smaller than that on the 1st day of initiating enteral nutrition(cm3:25.03±4.69 vs.28.68±5.96,P<0.05).③A comparative analysis was conducted among the three groups,revealing significant variations in the values of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),indirect bilirubin(IBil),alkaline phosphatase(ALP),γ-glutamyltranspeptidase(γ-GT),and gallbladder volume across the groups.From 1-7 days following the initiation of enteral nutrition,the bile-related indexes in the nasoenteric tube group exhibited an increasing trend,while the bile-related indexes in the mixed nutrition group demonstrated a decreasing trend.④ Spearman correlation analysis showed that gallbladder volume was significantly and positively correlated with AST,ALT,ALP,and γ-GT(r values of 0.398,0.299,0.242,and 0.262,respectively,all P<0.01).⑤ Multivariate Logistic regression analysis demonstrated that the initiation of enteral nutrition for 7 days was associated with a significant advantage,as indicated by an odds ratio(OR)of 1.031,with a 95%confidence interval(95%CI)of 1.004-1.058,and a P value was 0.024.Furthermore,the initiation of enteral nutrition for 7 d AST(OR=1.031,95%CI was 1.004-1.058,P=0.024),TBil(OR=1.187,95%CI was 1.039-1.355,P=0.011),and IBil(OR=0.707,95%CI was 0.542-0.921,P=0.010),and γ-GT(OR=0.985,95%CI was 0.972-0.999,P=0.034)were all factors affecting the survival of ICU patients during hospitalisation.Conclusions In the context of patients receiving intensive care,the prolonged utilisation of nasoenteric feeding tubes for a duration exceeding seven days has been observed to potentially induce an augmentation in gallbladder volume and an elevation in biliary-related indices,including ALT,AST,ALP,and γ-GT.The concomitant administration of nasogastric feeding,grounded in the foundation of simple nasoenteric tube nutrition,has been demonstrated to result in a reduction of these biliary-related indices to a certain extent.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVES: To study the impact of family socioeconomic status on children's reading fluency and the chain mediation effect of family reading environment and children's living and learning styles in this relationship. METHODS: A total of 473 children from grades 2 to 6 in two primary schools in Nanjing were selected through stratified random sampling. The children's reading fluency was assessed, and a questionnaire was used to collect information on family socioeconomic status, family reading environment, and children's living and learning styles. The mediation model was established using the Process macro in SPSS, and the Bootstrap method was employed to test the significance of the mediation effects. RESULTS: Family socioeconomic status, family reading environment, and children's living and learning styles were significantly positively correlated with reading fluency (P<0.001). The family reading environment and children's living and learning styles mediated the relationship between family socioeconomic status and children's reading fluency. Specifically, the independent mediation effect of family reading environment accounted for 11.02% of the total effect, while the independent mediation effect of children's living and learning styles accounted for 10.79%. The chain mediation effect of family reading environment and children's living and learning styles accounted for 7.41% of the total effect. CONCLUSIONS Family socioeconomic status can affect children's reading fluency through three pathways: family reading environment, children's living and learning styles, and the chain mediation effect of family reading environment and children's living and learning styles.
Humans ; Child ; Male ; Female ; Reading ; Learning ; Social Class ; Family

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Traditional Chinese medicine(TCM)serves as a treasure trove of ancient knowledge,holding a crucial position in the medical field.However,the exploration of TCM's extensive information has been hindered by challenges related to data standardization,completeness,and accuracy,primarily due to the decen-tralized distribution of TCM resources.To address these issues,we developed a platform for TCM knowledge discovery(TCMKD,https://cbcb.cdutcm.edu.cn/TCMKD/).Seven types of data,including syndromes,formulas,Chinese patent drugs(CPDs),Chinese medicinal materials(CMMs),ingredients,targets,and diseases,were manually proofread and consolidated within TCMKD.To strengthen the integration of TCM with modern medicine,TCMKD employs analytical methods such as TCM data mining,enrichment analysis,and network localization and separation.These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights.In addition to its analytical capabilities,a quick question and answer(Q&A)system is also embedded within TCMKD to query the database efficiently,thereby improving the interactivity of the platform.The platform also provides a TCM text annotation tool,offering a simple and efficient method for TCM text mining.Overall,TCMKD not only has the potential to become a pivotal repository for TCM,delving into the pharmaco-logical foundations of TCM treatments,but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems,extending beyond just TCM.