Objective To study the relationship between the mandibular bone arch and the dental arch in patients with skeletal Class Ⅱ malocclusion and compare it with the Class Imalocclusion by establishing a 3D digital model.Methods A total of 25 cases with skeletal Class Ⅱ malocclusion and 25 cases with skeletal Class Ⅰ normal occlusion were selected.The mandibular model was scanned and a three-dimensional digital model was set up.After the determination of the WALA ridge and the FA point,the reference plane and coordinate system was established.Four degree polynomial curve fitting was performed with WALA ridge and FA point coordinates to re-present the corresponding basal and dental arch curves.The width difference between the basal arch curve and the dental arch curve was measured and calculated at 3 mm,10 mm,and 18 mm away from the horizontal axis of the coordinate.The differences of basal bone and dental arch width between skeletal Class Ⅱ and skeletal Class Ⅰ malocclusion was compared.Results The width differences be-tween the arch and the dental arch in the anterior,middle and posterior mandibular segments of skeletal Class Ⅱ patients were-1.58 mm,1.80 mm and 3.80 mm,respectively.The width differences between the arch and the dental arch in the anterior,middle and pos-terior mandibular segments of skeletal Class Ⅰ patients were 2.08 mm,2.92 mm and 4.24 mm,respectively.There was a significant difference between skeletal Class Ⅱ and skeletal Class Ⅰ in the anterior and middle segments(P＜0.05),but no significant difference in the posterior segment(P＞0.05).Conclusion In skeletal Class Ⅰ patients,the width of the basal bone is larger than that of the dental arch,and the dental arch was located medial to the basal bone.In skeletal Class Ⅱ patients,the width of the anterior arch is larger than the width of the basal bone,that is,the dental arch is located outside the basal bone.The width difference of the basal arch in skeletal Class Ⅱ is smaller than that in skeletal Class Ⅰ.

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

A 7-year-old girl was admitted to the hospital with rapidly progressive vision loss. Since 1 year of age, she had exhibited developmental delay accompanied by visual impairment and neutropenia. Combined with genetic testing and molecular pathogenicity analysis, she was diagnosed with Cohen syndrome (CS) caused by compound heterozygous variants in VPS13B (c.6940+1G>T and c.2911C>T). The c.6940+1G>T variant resulted in exon 38 skipping, leading to a frameshift and premature termination. Reverse transcription quantitative polymerase chain reaction revealed significantly reduced VPS13B gene expression (P<0.05). Bioinformatic analysis suggested that both variants likely produce truncated proteins. This case highlights that integrating clinical features with molecular pathogenicity assessment (DNA, RNA, and protein analysis) can improve early diagnostic accuracy for CS.
Humans ; Female ; Child ; Vesicular Transport Proteins/genetics* ; Developmental Disabilities/etiology* ; Muscle Hypotonia/etiology* ; Myopia/etiology* ; Heterozygote ; Intellectual Disability/etiology* ; Microcephaly/etiology* ; Obesity/genetics* ; Growth Disorders/etiology* ; Retinal Degeneration/genetics* ; Psychomotor Disorders/genetics* ; Fingers/abnormalities*

Objective To investigate the effect of sal-like gene 2(Sall2)gene overexpression on the progression of disease in human superoxide dismutase 1(hSOD1)-G93A mutant amyotrophic lateral sclerosis(ALS)transgenic mice,with the aim of identifying potential therapeutic targets for ALS gene therapy.Methods Differential Sall2 gene were screened through bioinformatics analysis.Forty-eight ALS transgenic mice were selected for this study.AAV-PHP.eB-Sall2 adeno-associated virus with a neuron-specific promoter,human synapsin I(hSyn),was constructed and administered via tail vein injection to six-week-old mice.In parallel,the same litter of ALS mice received an injection of AAV-PHP.eB-GFP.The staining of Sall2 and neuron-specific nuclear protein(NeuN)/GFAP in the spinal cord and cerebral cortex of mice were detected through immunofluorescent double-label staining technology.The survival period,weight changes,exercise ability,and electromyographic changes of the gastrocnemius muscle were detected.The morphological changes in the spinal cord anterior horn neurons were detected through Nissl staining.The effect of Sall2 gene overexpression on the expression of the cell cycle protein E1(cyclin E1)was investigated through Western blotting.Results Bioinformatics analysis showed out that Sall2 was differentially expressed in ALS mice.Compared with ALS mice in the control group,the Sall2 protein expression of ALS mice in the overexpressing Sall2 gene group increased in both the spinal cord and cerebral cortex,and the Sall2 integral absorbance values of Sall2+/NeuN+double-positive cells were higher.The survival time of ALS mice in the Sall2 gene overexpressing group was prolonged,the rate of weight loss was slowed down,the performance in the rotarod and inverted grid tests was improved with longer times,and the positive sharp waves and fibrillation potentials in the gastrocnemius electromyography were reduced.The number of Nissl bodies labeled neurons increased in the spinal cord anterior horn of the Sall2 gene overexpressing mice,and the condition of neuronal damage was improved.Overexpression of the Sall2 gene also reduced the expression of cyclin E1 in both the spinal cord and cerebral cortex of ALS transgenic mice.Conclusion Overexpression of the Sall2 gene can delay disease progression and improve motor performance in ALS transgenic mice,affecting the expression of cyclin E1,thus exerting a therapeutic effect on these mice.

Objective To explore the role of SLIT-ROBO Rho GTPase-activating protein 2(srGAP2)in spinal motor neuron degeneration in amyotrophic lateral sclerosis(ALS).Methods Applied bioinformatics analysis to investigate the expression changes of srGAP2 in the spinal cord of human superoxide dismutase 1(hSOD1)mutant ALS transgenic mice.hSOD1 G93A mutant ALS transgenic mice were selected for animal experimental validation,with littermate wild type(WT)mice serving as the control group.A total of 36 pairs were divided into four groups,namely the pre-onset stage,early-onset stage,mid-onset stage,and late-onset stage.The expression changes and cellular localization of srGAP2 in the spinal cord of ALS mice were detected by Real-time PCR,Western blotting and immunofluorescent double-label staining.The hSOD1G93A mutant NSC34 motor neuron-like cell model was established,and in vitro experiments were carried out to detect the changes in srGAP2 expression,and the effects of srGAP2 over-expression on the viability of hSOD1G93A mutant NSC34 cells and the growth of cell protrusions.Results Bioinformatics analysis revealed abnormally low expression of srGAP2 in the spinal cord of hSOD1 mutant ALS mice.Animal experiments verified that compared with the WT mice,the expression of srGAP2 was reduced at both mRNA level and protein level in the spinal cord of hSOD1G93A mutant ALS transgenic mice at early-onset,mid-onset and late-onset stages.Compared with the WT mice,srGAP2 integral absorbance(IA)values in srGAP2+/NeuN+double-positive cells in the anterior horn of the spinal cord of hSOD1G93A mutant ALS transgenic mice were lower,srGAP2 IA values in srGAP2+/GFAP+double-positive cells were higher;Compared with the hSOD1WT NSC34 cells,the expression of srGAP2 was reduced at both mRNA level and protein level in hSOD1G93A mutant NSC34 cells.Over-expression of srGAP2 elevated the viability of hSOD1G93A mutant NSC34 cells,and up-regulated the expression level of synapse-related protein β Ⅲ-tubulin and growth associated protein 43(GAP43).Conclusion Low expression of srGAP2 is closely associated with the progression of ALS,while over-expression of srGAP2 can promote outgrowth of cell protrusions and exert a protective effect on spinal motor neurons in ALS.

Objective To evaluate the influence of the wearing position of dosimeters outside lead aprons on effective dose estimation for interventional radiology workers, analyze the differences between single and double dosimeter methods in effective dose estimation, and provide a reference for the personal dose monitoring of interventional radiology workers. Methods This study employed a combined approach of on-site monitoring and Monte Carlo simulation to evaluate the impact of the wearing position of dosimeters outside lead aprons on effective dose estimation, as well as the differences between effective doses measured using single and double dosimeters. Interventional radiology workers wore dosimeters at three positions: the neck outside the lead collar, the left chest outside the lead apron, and inside the lead apron. Effective doses were estimated using the single and double dosimeter methods specified in GBZ 128-2019 Specifications for individual monitoring of occupational external exposure, and the impact of different wearing positions on the estimation results was compared. Geant4 Monte Carlo simulations were used to model dose distributions at the neck outside the lead collar and at the left chest outside the lead apron for operators performing cardiovascular interventions under tube voltages of 70, 80, 90, and 100 kVp and exposure angles of posteroanterior (PA), anteroposterior (AP), and left anterior oblique 45° (LAO45°) positions. The study assessed the impact of dosimeter wearing position on effective dose estimation. Results Monte Carlo simulations demonstrated that neck doses consistently exceeded left chest doses across different tube voltages and exposure angles, with neck-to-chest dose ratios of 0.80-0.90. Under identical tube voltage conditions, AP showed the highest doses, followed by LAO45°, and PA demonstrated the lowest doses. The single and double dosimeter methods exhibited consistent patterns in effective dose estimation. Single dosimeter method generally yielded higher effective doses with relative deviations of 9.9% to 83%, though these deviations decreased under high tube voltages. Field monitoring data indicated that most interventional radiology workers maintained relative deviations between single and double dosimeter calculations below 6%, with neck-to-chest dose ratios of 0.95-1.1. The estimation patterns remained consistent across both methods, though single dosimeter method showed slightly higher results. Conclusion Under PA, AP, or LAO45°, the doses at the neck consistently exceeded those at the left chest. Therefore, when wearing lead protective equipment, the dosimeter should be properly positioned at the neck outside the lead collar to accurately reflect the radiation doses of surgeons. Some interventional radiology workers improperly positioned the dosimeter (intended at the neck outside the lead collar) at the left chest outside the lead apron, and this may result in an underestimation of the effective dose.

Objective To study the relationship between the mandibular bone arch and the dental arch in patients with skeletal Class Ⅱ malocclusion and compare it with the Class Imalocclusion by establishing a 3D digital model.Methods A total of 25 cases with skeletal Class Ⅱ malocclusion and 25 cases with skeletal Class Ⅰ normal occlusion were selected.The mandibular model was scanned and a three-dimensional digital model was set up.After the determination of the WALA ridge and the FA point,the reference plane and coordinate system was established.Four degree polynomial curve fitting was performed with WALA ridge and FA point coordinates to re-present the corresponding basal and dental arch curves.The width difference between the basal arch curve and the dental arch curve was measured and calculated at 3 mm,10 mm,and 18 mm away from the horizontal axis of the coordinate.The differences of basal bone and dental arch width between skeletal Class Ⅱ and skeletal Class Ⅰ malocclusion was compared.Results The width differences be-tween the arch and the dental arch in the anterior,middle and posterior mandibular segments of skeletal Class Ⅱ patients were-1.58 mm,1.80 mm and 3.80 mm,respectively.The width differences between the arch and the dental arch in the anterior,middle and pos-terior mandibular segments of skeletal Class Ⅰ patients were 2.08 mm,2.92 mm and 4.24 mm,respectively.There was a significant difference between skeletal Class Ⅱ and skeletal Class Ⅰ in the anterior and middle segments(P＜0.05),but no significant difference in the posterior segment(P＞0.05).Conclusion In skeletal Class Ⅰ patients,the width of the basal bone is larger than that of the dental arch,and the dental arch was located medial to the basal bone.In skeletal Class Ⅱ patients,the width of the anterior arch is larger than the width of the basal bone,that is,the dental arch is located outside the basal bone.The width difference of the basal arch in skeletal Class Ⅱ is smaller than that in skeletal Class Ⅰ.

Objective To investigate the rehabilitative effects of pelvic floor muscle training(PFMT)combined with electromyography biofeedback(EMG-BF)in patients with post-prostatectomy incontinence(PPI),aims to provide refer-ence for clinical nursing practice.Methods 98 patients with PPI who were treated at the urinary incontinence nurse-led clinic of a tertiary hospital in Shanghai were included using the method of convenience sampling.Patients enrolled from June to September 2022 were assigned to a control group(n=49),receiving PFMT alone at home.Those enrolled from November 2022 to February 2023 were assigned to an experimental group(n=49),receiving PFMT at home combined with EMG-BF at the nurse-led clinic.Both groups received intervention for 3 months,preceded by guidance for PFMT provided by incontinence specialist nurses.The urine leakage in 24-hour pad test,the International Consultation on Incontinence Questionnaire-Short Form(ICIQ-SF),the Incontinence Quality of Life Questionnaires(I-QOL),and the Broome Pelvic Muscle Self-Efficacy Scale(BPMSES)were used to assess objective and subjective incontinence severity,quality of life,and self-efficacy of PFMT on the day of catheter removal and at 1,2,and 3 months post-intervention.Results A total of 46 patients were included in each group.The 24-hour urine leakage volume and I-QOL scores demonstrated significant between-group and over-time effects(P＜0.05),with no interaction effect between groups and time(P＞0.05)The ICIQ-SF and BPMSES scores exhibited interactive ef-fects between time and groups(P＜0.05).At 2 and 3 months post-intervention,the intervention group showed signifi-cantly lower ICIQ-SF scores(P＜0.001),and higher BPMSES scores(P＜0.05),compared to those in the control group.Conclusion PFMT combined with EMG-BF can effectively alleviate the objective and subjective severity of PPI,enhance patients'self-efficacy in PFMT,and improve their postoperative quality of life.