Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

Objective:To investigate the characteristics of gut microbiota distribution in children with cyclic vomiting syndrome（CVS）complicated by constipation.Methods:The children with CVS, aged from 1 to 16 years, who were admitted to Beijing Tsinghua Changgung Hospital from June 2022 to January 2024, were divided into constipation group and normal group(non-constipation group) according to whether they were complicated with constipation or not.The clinical data and stool samples of children were collect. The abundance, diversity and composition of intestinal flora in fecal samples of two groups were detected by metagenomics sequencing.Results:A total of 20 children with CVS were collected, including 10 patients in constipation group and 10 patients in normal group.There were no significant differences in general demographic data between the two groups, including age at admission, age at first onset, body mass index, gender distribution, disease severity, endoscopic findings, and abdominal pain patterns.Microbiome analysis yielded 470 operational taxonomic units (OTUs), with 414 OTUs identified in normal group and 56 OTUs in constipation group. The abundance and diversity of intestinal flora in constipation group were significantly lower than those in normal group. Principal coordinate analysis and principal component analysis indicated significant structural differences in gut microbiota composition between the two groups. LEfSe analysis revealed distinct taxonomic patterns between the two groups, with the normal group demonstrating predominant representation of Firmicutes at the phylum level, while the constipation group showed higher relative abundance of Bacteroidetes and Actinobacteria. KEGG pathway analysis revealed that the carbon metabolism pathways was significantly enriched in the constipation group.Conclusion:There are significant differences in intestinal flora between CVS children with and without comorbid constipation.Bacteroides and Actinomycetes play an important role in constipation of children with CVS. The diversity and metabolic function of intestinal flora may be one of the pathological mechanisms of CVS complicated with constipation.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

Objective:This study aims to explore the application effect of anticipatory risk intervention combined with health education under LEARNS mode in elderly patients with chronic heart failure(CHF).Methods:This randomized controlled enrolled 126 elderly CHF patients admitted in Panzhihua Central Hospital between January 2022 and February 2023.They were divided into control group(n=63)and intervention group(n=63).All patients received routine nursing care,patients in control group received additional health education under LEARNS mode,compared to those in intervention group receiving additional anticipatory risk intervention based on control group,both groups were intervened for 2 months.Physiological indexes,negative emotion,quality of life,sleep quality,disease perception&control and self-efficacy,as well as incidence of adverse events,were compared between two groups.Results:Compared with patients in control group after intervention,those in intervention group had signif-icant lower systolic blood pressure(SBP)[(119.84±8.60)mmHg vs.(129.49±9.24)mmHg],diastolic blood pressure(DBP)[(81.59±5.08)mmHg vs.(88.51±6.36)mmHg],N terminal pro brain natriuretic peptide(NT-proBNP)[(2604.46±204.80)ng/L vs.(3024.87±212.27)ng/L],scores of Self-Rating Anxiety Scale(SAS)[(55.90±2.43)points vs.(60.11±2.62)points],Self-Rating Depression Scale(SDS)[(57.03±2.56)points vs.(61.54±2.66)points],Minnesota Living with Heart Failure Questionnaire(MLHFQ)[(52.05±6.32)points vs.(60.46±7.10)points]and Pittsburgh Sleep Quality Index(PSQI)[(9.00±1.65)points vs.(11.05±1.96)points],and significant higher left ventricular ejection fraction(LVEF)[(51.83±7.28)％vs.(47.57±5.98)％],scores of Control Attitude Scale-Revised(CAS-R)[(35.59±2.97)points vs.(30.60±3.52)points]and Gen-eral Self-Efficacy Scale(GSES)[(36.98±4.21)points vs.(30.52±4.14)points](P＜0.001 all).Incidence of adverse events in intervention group was significantly lower than that of control group(3.17％vs.12.70％,P=0.048).Conclusion:Anticipatory risk intervention combined with health education under the LEARNS model could effectively improve the physiological indexes,quality of life and sleep,enhance disease perception and self-effica-cy,and reduce negative emotion and incidence of adverse events in elderly CHF patients.

Objective:To investigate the characteristics of gut microbiota distribution in children with cyclic vomiting syndrome（CVS）complicated by constipation.Methods:The children with CVS, aged from 1 to 16 years, who were admitted to Beijing Tsinghua Changgung Hospital from June 2022 to January 2024, were divided into constipation group and normal group(non-constipation group) according to whether they were complicated with constipation or not.The clinical data and stool samples of children were collect. The abundance, diversity and composition of intestinal flora in fecal samples of two groups were detected by metagenomics sequencing.Results:A total of 20 children with CVS were collected, including 10 patients in constipation group and 10 patients in normal group.There were no significant differences in general demographic data between the two groups, including age at admission, age at first onset, body mass index, gender distribution, disease severity, endoscopic findings, and abdominal pain patterns.Microbiome analysis yielded 470 operational taxonomic units (OTUs), with 414 OTUs identified in normal group and 56 OTUs in constipation group. The abundance and diversity of intestinal flora in constipation group were significantly lower than those in normal group. Principal coordinate analysis and principal component analysis indicated significant structural differences in gut microbiota composition between the two groups. LEfSe analysis revealed distinct taxonomic patterns between the two groups, with the normal group demonstrating predominant representation of Firmicutes at the phylum level, while the constipation group showed higher relative abundance of Bacteroidetes and Actinobacteria. KEGG pathway analysis revealed that the carbon metabolism pathways was significantly enriched in the constipation group.Conclusion:There are significant differences in intestinal flora between CVS children with and without comorbid constipation.Bacteroides and Actinomycetes play an important role in constipation of children with CVS. The diversity and metabolic function of intestinal flora may be one of the pathological mechanisms of CVS complicated with constipation.

Patent foramen ovale(PFO)demonstrates significant comorbidity with migraine,but its causal relationship and the efficacy of transcatheter closure remain controversial.This systematic review examines potential biomarkers and relevant imaging assessments for PFO-associated migraine,aiming to provide a theoretical foundation for clinical diagnosis and treatment.Key biomarkers include platelet activation markers,calcitonin gene-related peptide,homocysteine,and platelet-to-lymphocyte ratio.Imaging evaluations encompass right-to-left shunt grading(transthoracic echocardiography,transcranial Doppler ultrasound),cerebrovascular breath-holding index,characteristics of white matter hyperintensities,alterations in resting-state functional magnetic resonance imaging(rs-f-MRI)brain networks,in-situ thrombi detected by optical coherence tomography,and electroencephalogram(EEG)power spectral features.Research indicates that integrating biomarkers with imaging technologies enhances diagnostic discrimination and treatment outcome prediction.Current challenges include unclear causal relationships and insufficient standardization of detection methods.Future efforts require multidisciplinary collaboration to establish personalized diagnostic and therapeutic frameworks through multimodal indicators,thereby advancing precise prevention and treatment strategies for PFO-related migraine.

Objective To investigate the prevalence of specific IgE antibodies against Alternaria alternata and Aspergillus fumigatus in serum samples from clinical allergy patients across selected provinces in China.Methods Data on specific IgE antibodies for Alternaria A.and Aspergillus F.were collected from 20 hospital laboratories in 17 cities spanning 11 provinces.The study analyzed the levels of specific IgE and their variations across different provinces and seasons.Results A total of 27 471 cases of Alternaria A.and 32 843 cases of Aspergillus F.specific IgE data were included.The national average positive rate of Alternaria A.IgE was 10.40%,with the highest rate of 22.68%in Jiangsu and the lowest rate of 2.06%in Guangxi.For Aspergillus F.specific IgE,the average positive rate was 4.24%,with Hubei province having the highest rate(7.25%)and Hunan province the lowest(1.23%).The difference in IgE levels for both Alternaria A.and Aspergillus F.among provinces were statistically significant(H=9 955,16 993,all P<0.0001).Among patients,5.85%had Alternaria A.specific IgE levels at grade 3 or above,while only 0.57%had Aspergillus F.specific IgE levels at this level.When examining seasonal variations using data from Liaoning,Hunan and Anhui provinces,significant seasonal changes were observed for both Alternaria A.and Aspergillus F.IgE antibodies(HAlternaria A=347.6,338.0,401.3,HAspergillus F=196.6,133.7,231.7,all P<0.0001).Conclusion The sensitization to Alternaria A.and Aspergillus F.exhibits distinct geographical characteristics and vary significantly with seasons.Given the relatively high IgE levels associated with Alternaria A.,it should be given adequate clinical attention.

Patent foramen ovale(PFO)demonstrates significant comorbidity with migraine,but its causal relationship and the efficacy of transcatheter closure remain controversial.This systematic review examines potential biomarkers and relevant imaging assessments for PFO-associated migraine,aiming to provide a theoretical foundation for clinical diagnosis and treatment.Key biomarkers include platelet activation markers,calcitonin gene-related peptide,homocysteine,and platelet-to-lymphocyte ratio.Imaging evaluations encompass right-to-left shunt grading(transthoracic echocardiography,transcranial Doppler ultrasound),cerebrovascular breath-holding index,characteristics of white matter hyperintensities,alterations in resting-state functional magnetic resonance imaging(rs-f-MRI)brain networks,in-situ thrombi detected by optical coherence tomography,and electroencephalogram(EEG)power spectral features.Research indicates that integrating biomarkers with imaging technologies enhances diagnostic discrimination and treatment outcome prediction.Current challenges include unclear causal relationships and insufficient standardization of detection methods.Future efforts require multidisciplinary collaboration to establish personalized diagnostic and therapeutic frameworks through multimodal indicators,thereby advancing precise prevention and treatment strategies for PFO-related migraine.

Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis