ObjectiveTo investigate the mechanisms by which Huanglian Jiedutang （HLJDT） modulates microglial （MG） phenotypes through the sialic acid-binding Ig-like lectin 2 （SIGLEC2/CD22）/Src-homology-2-domain-containing protein tyrosine phosphatase-1 （SHP-1）/phosphorylated protein kinase B （p-Akt） signaling pathway， thereby promoting myelin repair and alleviating agitation-like behaviors in vascular dementia （VAD）. MethodsSixty C57BL/6J mice were randomly assigned to a sham （normal） group， model group， HLJDT low-， medium-， and high-dose groups （2.5， 5， and 10 g·kg^-1·d^-1）， and a risperidone group （2 mg·kg^-1·d^-1）， with 10 mice per group. VAD was induced by bilateral common carotid artery stenosis （BCAS）. From day 42， mice received drug interventions for 2 weeks. Agitation-like behaviors were assessed using the resident-intruder test. After behavioral testing， ventrolateral part of the ventromedial hypothalamus （VMHvl） tissues were collected. Western blot was used to measure protein levels of myelin oligodendrocyte glycoprotein （MOG）， myelin basic protein （MBP）， proteolipid protein （PLP）， inducible nitric oxide synthase （iNOS）， arginase-1 （Arg1）， CD86， CD206， and CD22， SHP-1， and p-Akt. Immunofluorescence was used to evaluate myelin-associated glycoprotein （MAG） intensity and the proportion of iNOS⁺/ionized calcium-binding adapter molecule 1 （Iba1）⁺ cells. ELISA was used to detect tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β. ResultsCompared with the normal group， the model group exhibited markedly increased biting and aggressive behaviors and shortened attack latency （P<0.01）. MOG， MBP， and PLP protein levels and MAG fluorescence intensity were significantly reduced （P<0.05， P<0.01）. INOS and CD86 expression and TNF-α， IL-6， and IL-1β levels were significantly elevated （P<0.01）. CD22 and SHP-1 expression increased significantly （P<0.01）， whereas p-Akt expression decreased （P<0.01）. Compared with the model group， the medium- and high-dose HLJDT groups and the risperidone group showed markedly reduced biting and aggression （P<0.05， P<0.01） and prolonged attack latency （P<0.01）. MOG， MBP， and PLP levels and MAG fluorescence intensity were significantly increased （P<0.05， P<0.01）. INOS， CD86， TNF-α， IL-6， and IL-1β levels decreased significantly （P<0.05， P<0.01）. CD22 and SHP-1 expression decreased， while p-Akt expression increased significantly （P<0.05， P<0.01）. ConclusionHLJDT may modulate CD22/SHP-1/p-Akt signaling in the VMHvl， promote the shift of MG toward an anti-inflammatory and phagocytic phenotype， enhance myelin repair， and improve agitation-like behaviors in VAD mice.

BackgroundNon-suicidal self-injury （NSSI） behavior among adolescents has become a global public health concern. Anxiety and depression are considered key factors influencing NSSI behavior， while social support may play a protective role in alleviating emotional and behavioral issues. However， existing research has primarily focused on the direct impact of individual factors on NSSI behavior， with insufficient exploration of the combined effects of anxiety， depression and social support. ObjectiveTo investigate the direct effect of anxiety on NSSI， the mediating role of depression and the moderating role of social support in relationship between anxiety and NSSI behavior， thus to provide references for the prevention and intervention of NSSI behavior among adolescents. MethodsIn February 2022， a total of 40 820 students in grades 7 to 12 across 10 middle schools in a district of Chengdu were selected as participants， and they were assessed using Generalized Anxiety Disorder Scale-7 item （GAD-7）， Patient's Health Questionnaire Depression Scale-9 item （PHQ-9）， Social Support Scale for Urban Students （SSSUS） and Adolescent Self-Harm Scale （ASHS）. Pearson correlation analysis was conducted to examine the correlations between scale scores among adolescents with NSSI behaviors. Mediation and moderation analyses were performed using Process 3.5 in SPSS， and the significance was tested with bootstrapping. The interaction was visualized by using simple slope analysis. ResultsAmong 34 534 （84.60%） valid respondents， 542 adolescents （1.57%） reported engaging in NSSI behavior. Significant differences in gender， GAD-7 scores， PHQ-9 scores， and SSSUS scores were observed between NSSI behavior group and non-NSSI group （χ²/t=62.889， 71.120， 94.365， -41.464， P<0.01）.Adolesents with NSSI showed positive correlations between GAD-7 scores and both ASHS and PHQ-9 scores （r=0.158， 0.166， P<0.01）. PHQ-9 scores were positively correlated with ASHS scores （r=0.364， P<0.01）， but negatively correlated with SSSUS scores （r=-0.290， P<0.01）. SSSUS scores were negatively correlated with ASHS scores （r=-0.247， P<0.01）. Depression partially mediated the relationship between anxiety and NSSI behavior， with an effect size of 0.544 （95% CI： 0.162~0.944）， accounting for 35.79% of the total effect. Social support moderated the relationship between depression and NSSI bahavior， with an effect value of -0.082 （95% CI： -0.135~-0.029）. ConclusionAnxiety not only directly influences NSSI bahavior among adolescents， also indirectly exacerbates it through depression， while social support mitigates the impact of depression on NSSI behavior. ［Funded by Youth Project of National Natural Science Foundation of China （number， 82401812）； Project of Health Commission of Sichuan Province （number， 24LCYJPT18）］

OBJECTIVE: To establish a similarity measurement model for patients with dentofacial deformity based on 3D craniofacial features and to validate the similarity results with quantifying subjective expert scoring. METHODS: In the study, 52 cases of patients with skeletal Class Ⅲ malocclusions who underwent bimaxillary surgery and preoperative orthodontic treatment at Peking University School and Hospital of Stomatology from January 2020 to December 2022, including 26 males and 26 females, were selected and divided into 2 groups by sex. One patient in each group was randomly selected as a reference sample, and the others were set as test samples. Three senior surgeons rated the similarity scores between the test samples and the reference sample. Similarity scores ranged from 1 to 10, where 1 was completely different, and 10 was exactly the same. Scores larger than 7.5 was considered as clinically similar. Preoperative cone beam computed tomography (CBCT) and 3D facial images of the patients were collected. The three-dimensional hard and soft tissue features, including distances, angles and 3D point cloud features were extracted. The similarity measurement model was then established to fit with the experts' similarity scoring by feature selection algorithm and linear regression model. To verify the reliability of the model, 14 new patients were selected and input to similarity measurement model for finding similar cases. The similarity scoring of these similar cases were rated by experts, and used to evaluate the reliability of the model. RESULTS: The similarity metric models indicated that the features of the middle and lower craniofacial features were the main features to influence the craniofacial similarity. The main features that were related to the expert' s similarity scoring included distance of anterior nasal spine-menton (ANS-Me), distance of right upper canion point-Frankfurt horizontal plane (U3RH), distance of left superior point of the condyle-left gonion (CoL-GoL), distance of left gonion-menton (CoL-Me), distance of pogonion-midsagittal plane (Pog-MSP), distance of right alar base-left alar base (AlR-AlL), angle of pronasale-soft tissue pogonion-labrale inferius (Pn-Pog' -Li), distance of trichion-right tragus (Tri-TraR), distance of left exocanthion-left alar base (ExL-AlL), lower 1/3 of skeletal face, middle and lower 2/3 of skeletal face and upper lip region of soft tissue. Fourteen new patients were chosen to evaluate the model. The similar cases selected by the model had an average experts' similarity scoring of 7.627± 0.711, which was not significantly different with 7.5. CONCLUSION The similarity measurement model established by this model could find the similar cases which highly matched experts' subjective similarity scoring. The study could be further used for similar cases retrieval in skeletal Ⅲ malocclusion patients.
Humans ; Male ; Female ; Imaging, Three-Dimensional/methods* ; Cone-Beam Computed Tomography ; Malocclusion, Angle Class III/surgery* ; Orthognathic Surgical Procedures/methods* ; Face/anatomy & histology* ; Cephalometry/methods* ; Adult ; Adolescent ; Dentofacial Deformities/surgery* ; Young Adult

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Small nuclear RNAs (snRNAs) refer to a class of highly abundant and functionally important non-coding small RNAs that are localized in the eukaryotic nucleus. These snRNAs are highly conserved in different eukaryotes during evolution and form complexes with specific chaperones to fulfill critical biological functions, including precursor messenger RNA (pre-mRNA) splicing and ribosomal RNA (rRNA) modification. Consequently, the regulation of snRNA gene expression is a crucial biological process for plants. In plants, the transcription and processing of snRNAs are regulated by RNA polymerase (Pol), snRNA-activating protein complex (SNAPc), defective in snRNA processing (DSP), and specific cis-elements in the snRNA promoter regions. Proper regulation of snRNA expression is essential for normal plant growth, development, and stress responses. This review summarizes the classification, structures, transcriptional regulation, and biological functions of plant snRNA genes, while outlining future research directions for snRNAs.
RNA, Small Nuclear/physiology* ; Gene Expression Regulation, Plant ; Transcription, Genetic ; Plants/metabolism* ; RNA, Plant/genetics*

BACKGROUND:Yougui Pill is a famous formula of the Chinese traditional medicine,which has good efficacy for lumbar disc herniation due to kidney yang insufficiency. OBJECTIVE:To investigate the potential targets and mechanism of action of Yougui Pill in the treatment of lumbar disc herniation by using network pharmacology and molecular docking technology,and verified by animal experiments. METHODS:(1)Network pharmacological analysis:We obtained the active ingredients and targets of Yougui Pill from TCMSP and other databases,collected genes related to lumbar disc herniation from GeneCards database,and took the intersection of the two for the topological analysis to derive the main active ingredients and core therapeutic targets.Gene ontology function analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using R software.(2)Molecular docking:Autodock and Pymol software were utilized for the prediction of molecular binding energy of TCM active ingredients to core therapeutic targets.(3)Animal experiments:Eighteen Sprague-Dawley rats were randomly divided into a control group,a degeneration group and a Yougui Pill group,with 6 rats in each group.A rat model of intervertebral disc degeneration was prepared by fiber puncture method in the degeneration and Yougui Pill groups.At 2 weeks after modeling,Yougui Pill was given by gavage in the Yougui Pill group,once a day for 2 consecutive weeks.The level of tumor necrosis factor-α in serum was detected by the ELISA method,and morphological changes of the annulus fibrosus and nucleus pulposus cells were observed using hematoxylin-eosin staining. RESULTS AND CONCLUSION:There were 90 active ingredients and 64 targets,and the main active ingredients were found to be quercetin,kaempferol,β-carotene,soybean flavonoid,and 4'-O-methylnyasol.The core targets of Yougui Pill for the treatment of lumbar disc herniation were interleukin 6,tumor necrosis factor-α,AKT1,interleukin 1B,and vascular endothelial growth factor A.Enrichment analysis revealed that the intersecting genes might be expressed through the interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,MAPK signaling pathway,PI3K-AKT signaling pathway,and other signaling pathways to improve intervertebral disc degeneration.The molecular docking test verified that quercetin,kaempferol,and β-carotene had strong binding ability to the core targets.Animal experiments showed that the level of serum tumor necrosis factor α in the degeneration group was higher than that in the control group(P<0.05),and the level of serum tumor necrosis factor α in the Yougui Pill group was lower than that in the degeneration group(P<0.05).Hematoxylin-eosin staining showed that the fibrous annulus of the intervertebral discs and the structure of the nucleus pulposus in the degeneration group were destroyed,and the number of nucleus pulposus cells was reduced;there was a tendency to reconstructing the fibrous annulus of the intervertebral discs in the Yougui Pill group,and the number of nucleus pulposus cells increased compared with the degeneration group.To conclude,Yougui Pill may treat lumbar disc herniation by improving disc degeneration through the effects of quercetin,kaempferol,beta-carotene and other key active ingredients on core targets such as tumor necrosis factor.

Objective:To explore the clinical epidemiological characteristics of respiratory syncytial virus in children in Hubei Province from 2020 to 2023.Method:A single-center and cross-sectional study was used to analyze the clinical data of 3 271 children with respiratory syncytial virus infection in Wuhan Children′s Hospital affiliated to Huazhong University of Science and Technology from July 1, 2020 to June 30, 2023. Nonparametric rank sum test and χ2 test were used for comparative analysis. Results:From July 1, 2020 to June 30, 2023, a total of 25 583 children were included in the analysis, of which 3 271(12.8%) children infected RSV. The detection rate was 16.3% in 2020-2021, 14.7% in 2021-2022 and 9.1% in 2022-2023. The detection rate decreased year by year ( χ2=222.054, P<0.05). From 2020 to 2023, there was an anti-seasonal epidemic of RSV in spring and autumn. The detection rate of RSV in infants under 1 year old was the highest, but the median ages of RSV positive children increased ( H=140.575, P<0.05). Pneumonia was the main clinical manifestation of RSV respiratory tract infection. Conclusion:The epidemiological characteristics of RSV in children in Hubei Province were different from those before. From 2020 to 2023, the detection rate of RSV decreased year by year. Besides winter, the prevalence of RSV could also be seen in spring and autumn. The median age of children infected with RSV increased after the epidemic. Pneumonia was the main clinical manifestation after RSV infection.

Objective Ionization chamber detector is commonly used for direct and continuous measurement of tritium concentration in the air. However, the measurement sensitivity is low due to the limitations of weak current measurement technology. It is necessary to develop a proportional counter for measuring tritium in the air. Methods This study involved the design of a proportional counter, considering various factors such as materials and structure. The stability, plateau curve, detection efficiency, and energy spectrum of the counter were tested. Results The coefficient of variation of the proportional counter was 3.14%, which met the standard requirement of being less than 15%. The plateau length was 260 V and the plateau slope was 0.80%/100V, which met the requirement of being less than 1%/100V. The tritium detection efficiency reached 68.02%. The energy spectrum measurement indicated a significant difference between tritium signal generated by the proportional counter and background signal, and the distribution of tritium in the energy spectrum was more concentrated. The background counting rate during tritium gas activity measurement could be reduced through energy spectrum measurement. Conclusion The proportional counter can provide a reference for the direct and continuous measurement of tritium in the air.

Objective To explore the correlation between serum fibroblast growth factor-23 (FGF23) concentration and heart failure and all-cause death in patients with end-stage renal disease (ESRD).Methods The prospective cohort study design was used in the present study.The ESRD patients who were admitted to the department of ne-phropathy in the Hospital and without heart failure symptoms were recruited in this study.The data of patients was collected through baseline questionnaires, physical examinations, echocardiography, and laboratory examinations.The serum FGF23 levels were measured by enzyme-linked immunosorbent assay (ELISA) .The follow-up time was 2 years.The onset of heart failure (ACC/AHA stage C-D) and all-cause death were composite endpoint events.The Cox proportional risk model was used to explore the risk factors of outcome events.Through subgroup analyses and interaction analyses, further exploration was conducted to determine whether there was heterogeneity in the as-sociation between FGF23 and outcome events in different subgroups.Results Ultimately,107 ESRD patients were included in this study, with an average age of (52.00 ± 12.51) years.There were 39 males (36.45％), and the median follow-up time was 23 months (21, 25 months).There were 32 (29.9％) outcome events, of which 22 (20.6％) onset of heart failure and 10 (9.3％) all-cause of deaths.The results of this study showed that the con-centration of FGF23 in the outcome event group was significantly higher than that in the non-event group [ (4.40 ± 1.16) pmol/ml vs (3.85 ± 0.82) pmol/ml,P<0.05].The Cox proportional risk model showed that the elevated FGF23 was associated with increased risk of the composite endpoint events in ESRD patients (HR=1.730 , 95％CI:1.164-2.570 , P=0.007) .Subgroup analyses showed that there was an interactive effect between FGF23 levels and gender on the risk of cardiovascular outcome events.Especially in male ESRD patients, the increased FGF23 level was correlated with a higher risk of cardiovascular events (P-interaction <0.05).Conclusion Elevated serum FGF23 is an independent risk factor for the onset of heart failure and all-cause of mortality in ESRD patients, especially in male patients.

BACKGROUND:To investigate the prognostic value of the peripheral perfusion index(PPI)in patients with septic shock. METHODS:This prospective cohort study,conducted at the emergency intensive care unit of Peking University People's Hospital,recruited 200 patients with septic shock between January 2023 and August 2023.These patients were divided into survival(n=84)and death(n=116)groups based on 28-day outcomes.Clinical evaluations included laboratory tests and clinical scores,with lactate and PPI values assessed upon admission to the emergency room and at 6 h and 12 h after admission.Risk factors associated with mortality were analyzed using univariate and multivariate Cox regression analyses.Receiver operator characteristic(ROC)curve was used to assess predictive performance.Mortality rates were compared,and Kaplan-Meier survival plots were created. RESULTS:Compared to the survival group,patients in the death group were older and had more severe liver damage and coagulation dysfunction,necessitating higher norepinephrine doses and increased fluid replacement.Higher lactate levels and lower PPI levels at 0 h,6 h,and 12 h were observed in the death group.Multivariate Cox regression identified prolonged prothrombin time(PT),decreased 6-h PPI and 12-h PPI as independent risk factors for death.The area under the curves for 6-h PPI and 12-h PPI were 0.802(95%CI 0.742-0.863,P<0.001)and 0.945(95%CI 0.915-0.974,P<0.001),respectively,which were superior to Glasgow Coma Scale(GCS),Sequential Organ Failure Assessment(SOFA)scores(0.864 and 0.928).Cumulative mortality in the low PPI groups at 6 h and 12 h was significantly higher than in the high PPI groups(6-h PPI:77.52%vs.22.54%;12-h PPI:92.04%vs.13.79%,P<0.001). CONCLUSION:PPI may have value in predicting 28-day mortality in patients with septic shock.