Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

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:To observe the inhibitory effect of dobutamine on proliferation of FLT3-ITD mutated acute myeloid leukemia(AML)cells and explore the feasibility of dobutamine as a monotherapy or in combination with quizartinib for the treatment of this type of AML.Methods:FLT3-ITD mutant cell lines MOLM13 and MV4-11 were cultured in vitro and divided into control group,dobutamine treatment group,quizartinib treatment group,and dobutamine combined with quizartinib treatment group.Cell viability,ROS levels,and apoptosis rate were detected by CCK-8,Flow cytometry,respectively,as well as the expression of YAP1 protein by Western blot.Results:Both dobutamine and quizartinib inhibited the proliferation of FLT3-ITD mutant AML cell lines.Compared with the control group,the dobutamine group exhibited a significant increase in ROS levels(P＜0.01),an increase in apoptosis rates(P＜0.05),and a decrease in YAP1 protein expression(P＜0.05).Compared with the dobutamine group,the combination of quizartinib and dobutamine significantly reduced cell viability(P＜0.05),increased ROS levels(P＜0.01),and decreased YAP1 expression(P＜0.05).Conclusion:Dobutamine as a monotherapy can inhibit the proliferation of FLT3-ITD mutated AML cells,inducing apoptosis.Additionally,the combination of quizartinib enhances the targeted inhibitory effect on FLT3-ITD mutated AML.The mechanism may involve the inhibition of YAP1 protein expression in AML cells of this type,leading to an increase in ROS levels and exerting its anti-tumor effects.

Objective:To investigate the effects of ubiquitin-specific protease (USP) 7/47 inhibitor (Cat. No. 1247825-37-1) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells with or without internal tandem duplications of the Flt3 gene (Flt3-ITD). Methods:ATP assay was used to detect the effects of 1247825-37-1 on the cell viability of two AML cell lines (MOLM13 and MV4-11) harboring Flt3-ITD mutation and one AML cell line (THP-1) without Flt3-ITD mutation as well as the primary Flt3-ITD-mutant and non-mutant AML cells from patient samples. Flow cytometry was used to detect the apoptosis of AML cell lines treated by different concentrations of 1247825-37-1.Results:Compared with the control group, 1247825-37-1 was able to significantly inhibit the proliferation of MOLM13, MV4-11 and THP-1 cells ( P<0.000 1). Besides, the cell viability of primary AML cells was also inhibited by 1247825-37-1, and a stronger inhibitory effect on non-mutant AML cells was observed. The USP7/USP47 inhibitor 1247825-37-1 could inhibit the proliferation of AML cells in a dose-dependent manner and a low dose (2 or 4 μmol/L) of 1247825-37-1 would be effective. Moreover, 1247825-37-1 was also able to efficiently induce the apoptosis of above AML cell lines in a dose-dependent manner. Conclusions:The USP7/USP47 inhibitor 1247825-37-1 significantly inhibits the proliferation of AML cells with or without Flt3-ITD mutation.

Objective: To explore sex differences in 3D T1texture features in the progression of Alzheimer's disease (AD) and to predict the diagnosis of AD patients of different sex． Methods: Seventy-seven AD patients (34 males and 42 females) ，74 amnestic mild cognitive impairment ( aMCI) patients ( 35 males and 39 females) and 75 healthy controls (HC) (35 males and 40 females) were recruited and high-resolution 3-dimensional T1 structural images were collected． Brain regions closely related to AD brain damage were selected as regions of interest ( ROIs) ，texture feature extraction and feature screening were performed．Analyses were performed by sex，and the support vector machine (SVM) was used for classification and prediction. Results : In the AD vs HC，AD vs aMCI and aMCI VS HC groups by different sex，we obtained some brain regions with relatively high recognition index in different subgroups，and found that there were significant differences between female patients and male patients with high recognition index，and the recognition index of female patients ( area under the curve，accuracy，sensitivity and specificity were generally higher than that of male． Conclusion There are significant sex differences in texture features in AD process，and the classification and prediction ability of texture features in female patients is better， suggesting the importance of sex differences in AD research．This study provides some reliable biomarkers for early sex-specific identification of AD，which may be helpful for the early diagnosis and treatment of AD in the future.

Objective: To investigate the effects of dopamine on olfactory function and inflammatory injury of olfactory bulb in mice with allergic rhinitis (AR). Methods: AR mouse model was established by using ovalbumin (OVA), and the mice were divided into two groups: olfactory dysfunction (OD) group and without OD group through buried food pellet test (BFPT). The OD mice were randomly divided into 2 groups, and OVA combined with dopamine (3, 6, 9 and 12 days, respectively) or OVA combined with an equal amount of PBS (the same treatment time) was administered nasally. The olfactory function of mice was evaluated by BFPT. The number of eosinophils and goblet cells in the nasal mucosa were detected by HE and PAS staining. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of olfactory marker protein (OMP) in olfactory epithelium, the important rate-limiting enzyme tyrosine hydroxylase (TH) of dopamine, and the marker proteins glial fibrillary acidic protein (GFAP) and CD11b of glial cell in the olfactory bulb. TUNEL staining was used to detect the damage of the olfactory bulb. SPSS 26.0 software was used for statistical analysis. Results: AR mice with OD had AR pathological characteristics. Compared with AR mice without OD, the expression of OMP in olfactory epithelium of AR mice with OD was reduced (F=26.09, P<0.05), the expression of GFAP and CD11b in the olfactory bulb was increased (F value was 38.95 and 71.71, respectively, both P<0.05), and the expression of TH in the olfactory bulb was decreased (F=77.00, P<0.05). Nasal administration of dopamine could shorten the time of food globule detection in mice to a certain extent, down-regulate the expression of GFAP and CD11b in the olfactory bulb (F value was 6.55 and 46.11, respectively, both P<0.05), and reduce the number of apoptotic cells in the olfactory bulb (F=25.64, P<0.05). But dopamine had no significant effect on the number of eosinophils and goblet cells in nasal mucosa (F value was 36.26 and 19.38, respectively, both P>0.05), and had no significant effect on the expression of OMP in the olfactory epithelium (F=55.27, P>0.05). Conclusion: Dopamine can improve olfactory function in mice with AR to a certain extent, possibly because of inhibiting the activation of glial cells in olfactory bulb and reducing the apoptotic injury of olfactory bulb cells.
Animals ; Disease Models, Animal ; Dopamine ; Humans ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa/metabolism* ; Olfactory Bulb/pathology* ; Ovalbumin ; Rhinitis, Allergic/metabolism*

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.
Child ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Malocclusion/prevention & control* ; Orthodontics, Interceptive

Objective:To explore the scheme of accurate pelvic osteotomy parameters and to analyze the feasibility and efficacy of 3D printing navigation plate in developmental dysplasia of the hip surgery.Methods:From January 2015 to December 2017, a total of 18 children with DDH underwent computer-assisted Salter pelvic osteotomy (computer-assisted osteotomy group) and 25 children with DDH who underwent conventional Salter pelvic osteotomy (conventional osteotomy group) were selected for retrospective analysis. There were 11 males and 32 females with an average age of 3.2±2.5 (range 1-11) years. According to International Hip Dysplasia Institute (IHDI) classification, there were 20 cases of type 1, 9 of type 2, 12 of type 3 and 2 of type 4. All patients were unilateral dislocation, including 18 cases on the left and 25 on the right. All children underwent pelvic CT examination before operation. Further, the proximal femur was surgically corrected during the operation. According to the acetabular rotation angle (ATA) and bony acetabular index (BAI), the computer-assisted osteotomy group simulated the operation with Mimics software made 3D printing navigation plate through which an accurate osteotomy scheme was developed. The two groups were compared in operative duration, intraoperative blood loss, Japanese Orthopaedic Association (JOA) hip joint score. Acetabular index (AI), central edge (CE) angle, and acetabulum head index (AHI) were compared between the two groups by using postoperative X-ray. The acetabular tilt angle (ATA) changes before and after operation in the computer-assisted osteotomy group were compared through 3D CT.Results:The follow-up duration was 2.3±0.2 (2.0 to 2.5) years in the computer-assisted osteotomy group and 2.8±0.15 (2.5 to 3.0) years in the conventional osteotomy group. The operative duration in the computer-assisted osteotomy group was 127±20.6 min, which was significantly longer ( t=4.657, P<0.001) than that in the conventional osteotomy group (103±13.2 min). Intraoperative bleeding was 157±17.5 ml in the computer-assisted osteotomy group and 151±15.3 ml in the conventional osteotomy group without significant difference between the two groups ( t=1.195, P=0.239). At 2 years after surgery, the JOA score of the hip joint in the computer-assisted osteotomy group (86.7±8.5 points) was like that (84.8±10.0 points) in the conventional osteotomy group ( t=0.628, P=0.533). At the last follow-up, the CE angle in the computer-assisted osteotomy group (36.8°±5.2°) was significantly larger than that (31.8°±4.4°) in the conventional osteotomy group ( t=3.414, P<0.001). There was statistically significant difference in term of AHI between the computer-assisted osteotomy group (85.8%±6.6%) and the conventional osteotomy group (80.4%±8.3%, t=2.284, P=0.028). AI was 23.5°±5.5° in the computer-assisted osteotomy group and 25.2°±4.2° in the conventional osteotomy group without significant difference ( t=-1.150, P=0.257). The ATA of the affected side was 12.3°±1.4° in the computer-assisted osteotomy group which was similar ( t=0.614, P=0.547) to that of the healthy side (11.8°±2.8°). Conclusion:Based on specific anatomical parameters, computer-assisted preoperative planning can not only directly simulate the process of osteotomy, but also produce individualized 3D printed guide plates. Compared with conventional Salter pelvic osteotomy, computer-assisted osteotomy can achieve accurate radiographic correction of the hip joint in children with DDH, resulting in a better matching relationship between the femoral head and acetabulum.

BACKGROUND: Finding an optimal treatment strategy for adolescent idiopathic scoliosis (AIS) patients remains challenging because of its intrinsic complexity. For mild to moderate scoliosis patients with lower skeletal growth potential (Risser 3-5), most clinicians agree with observation treatment; however, the curve progression that occurs during puberty, the adolescent period, and even in adulthood, remains a challenging issue for clinicians. The aim of the study is to investigate the efficacy of Schroth exercise in AIS patients with lower skeletal growth potential (Risser 3-5) and moderate scoliosis (Cobb angle 20°-40°). METHODS: From 2015 to 2017, data of 64 patients diagnosed with AIS in Peking University Third Hospital were reviewed. Forty-three patients underwent Schroth exercise were classified as Schroth group, and 21 patients underwent observation were classified as observation group. Outcomes were measured by health-related quality of life (HRQOL) and radiographic parameters. HRQOL was assessed using the visual analog scale (VAS) scores for back, Scoliosis Research Society-22 (SRS-22) patient questionnaire. Radiographic spinopelvic parameters were obtained from anteroposterior and lateral X-rays. The pre-treatment and post-treatment HRQOL and radiographic parameters were tested to validate Schroth exercise efficacy. The inter-rater reliability of the radiographic parameters was tested using the interclass correlation coefficient (ICC). The paired t test was used to examine HRQOL and radiographic parameters. Clinical relevance between C2-C7 sagittal vertical axis (SVA) and thoracic kyphosis was analyzed using Spearman correlation. RESULTS: In Schroth group, VAS back score, SRS-22 pain, and SRS-22 self-image domain were significantly improved from pre-treatment 3.0 ± 0.8, 3.6 ± 0.5, and 3.5 ± 0.7 to post-treatment 1.6 ± 0.6 (t = 5.578, P = 0.013), 4.0 ± 0.3 (t = -3.918, P = 0.001), and 3.7 ± 0.4 (t = -6.468, P < 0.001), respectively. No significant improvements of SRS-22 function domain (t = -2.825, P = 0.088) and mental health domain (t = -3.174, P = 0.061) were observed. The mean Cobb angle decreased from 28.9 ± 5.5° to 26.3 ± 5.2° at the final follow-up, despite no statistical significance was observed (t = 1.853, P = 0.102). The mean C2-C7 SVA value decreased from 21.7 ± 8.4 mm to 17.0 ± 8.0 mm (t = -1.224 P = 0.049) and mean T1 tilt decreased from 4.9 ± 4.2 ° to 3.5 ± 3.1° (t = 2.913, P = 0.011). No significant improvement of radiographic parameters and HRQOL were observed in observation group. CONCLUSIONS For AIS patients with a Risser 3-5 and a Cobb angle 20°-40°, Schroth exercises improved HRQOL and halted curve progression during the follow-up period. Both cervical spine alignment and shoulder balance were also significantly improved after Schroth exercises. We recommend Schroth exercises for patients with AIS.
Adolescent ; Adult ; Cervical Vertebrae ; Humans ; Kyphosis ; Lordosis ; Quality of Life ; Reproducibility of Results ; Retrospective Studies ; Scoliosis/therapy* ; Treatment Outcome