G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective:To measure the length and curvature of the external auditory canal (EAC) centerline using a three-dimensional (3D) measurement method based on high-resolution computed tomography (HRCT).Methods:A retrospective analysis was conducted on HRCT images of healthy EAC from 49 patients (64 ears) examined at the Sixth Medical Center of the PLA General Hospital from June to October 2024. The cohort included 25 males (28 ears) and 24 females (36 ears), aged 22-78 years (mean age 47.3 years), categorized into age groups: 18-30 years (20 ears), 31-60 years (22 ears), and 61-80 years (22 ears). The EAC comprised 29 left and 35 right ears. 3D reconstruction of the EAC was performed using medical software (3D Slicer), and the central curve of the EAC was extracted using an improved measurement method to determine its length and curvature. Statistical analysis was performed using Origin Pro 2023 software to compare differences across genders, sides, and age groups.Results:The measurements of EAC length and curvature revealed that the EAC was significantly longer in males than in females (27.46 mm vs. 25.44 mm, P=0.014) and longer on the right side than on the left (27.99 mm vs. 25.87 mm, P=0.031). No statistically significant difference in EAC length was observed among the different age groups ( P>0.05). Furthermore, no statistically significant differences in EAC curvature were found regarding gender, side, or age group (all P>0.05). Conclusion:The HRCT-based 3D reconstruction technique enables the establishment of a rapid and effective automated workflow for extracting the central curve of the EAC and systematically measuring its length and curvature. The data obtained provide a reference and methodological support for further research on anatomical variations of the human EAC and its potential clinical applications, such as the design of otological instruments or surgical planning.

Objective:To explore the association between oral health status, the lower respiratory tract microbiome, and the frequent acute exacerbation phenotype in chronic obstructive pulmonary disease (COPD).Methods:This cross-sectional study enrolled 39 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalized in the Department of Respiratory Medicine, Henan Provincial People′s Hospital between March 2021 and December 2022. Based on the number of hospitalization episodes for acute exacerbation in the past year, patients were divided into a frequent exacerbator group (≥2 times, n=28) and a non-frequent exacerbator group (<2 times, n=11). Bronchoalveolar lavage fluid (BALF) samples were collected from all subjects for metagenomic next-generation sequencing (mNGS). Oral health indicators and clinical data were also collected. Statistical analyses were performed using Spearman correlation analysis and multivariable Firth logistic regression analysis. Results:The frequent exacerbation group showed a significantly higher percentage of individuals with≥8 tooth loss compared to the non-frequent exacerbation group (96.4% vs 18.2%, P<0.001), a significantly younger age at first tooth loss in adulthood (53.96±7.30 years vs 62.10±5.80 years, P=0.003), and a significantly higher proportion of individuals who hardly brushed their teeth (50.00% vs 9.09%, P=0.038). The alpha-diversity indices of the lower respiratory tract microbiota were significantly lower in the frequent exacerbation group than in the non-frequent exacerbation group (all P<0.01). The relative abundances of Bacillota, Bacteroidota, Fusobacteriota, Streptococcus, Prevotella, Veillonella, Neisseria, Rothia, Prevotellamelaninogenica, Prevotellajejuni, Rothia mucilaginosa, Veillonella parvula, and Neisseria subflava were lower in the frequent exacerbation group (all P<0.05). In patients with AECOPD, the exacerbation frequency and the presence of ≥8 tooth loss were both negatively correlated with the Shannon index ( r=-0.854, P<0.001; r=-0.642, P<0.001, respectively). Further analysis revealed that Bacillota ( r=-0.862, P<0.001) and Streptococcus ( r=-0.814, P<0.001) were significantly negatively correlated with exacerbation frequency, while Pseudomonas was positively correlated with exacerbation frequency (all P<0.05). Bacillota ( r=0.369, P=0.021), Fusobacteriota ( r=0.368, P=0.021), and Veillonella ( r=0.379, P=0.017) were positively correlated with FEV 1% predicted. Multivariable Firth logistic regression analysis revealed that the first principal component of the microbial community ( OR=2.29, 95% CI: 1.20-11.07) and the loss of≥8 teeth ( OR=14.37, 95% CI: 1.42-482.51) were independent factors associated with frequent acute exacerbations. Conclusion:Frequent acute exacerbations of COPD are significant association with deteriorated oral health and dysbiosis of the lower respiratory tract microbiome, characterized by reduced alpha-diversity and depletion of commensal bacteria.

Objective:To measure the length and curvature of the external auditory canal (EAC) centerline using a three-dimensional (3D) measurement method based on high-resolution computed tomography (HRCT).Methods:A retrospective analysis was conducted on HRCT images of healthy EAC from 49 patients (64 ears) examined at the Sixth Medical Center of the PLA General Hospital from June to October 2024. The cohort included 25 males (28 ears) and 24 females (36 ears), aged 22-78 years (mean age 47.3 years), categorized into age groups: 18-30 years (20 ears), 31-60 years (22 ears), and 61-80 years (22 ears). The EAC comprised 29 left and 35 right ears. 3D reconstruction of the EAC was performed using medical software (3D Slicer), and the central curve of the EAC was extracted using an improved measurement method to determine its length and curvature. Statistical analysis was performed using Origin Pro 2023 software to compare differences across genders, sides, and age groups.Results:The measurements of EAC length and curvature revealed that the EAC was significantly longer in males than in females (27.46 mm vs. 25.44 mm, P=0.014) and longer on the right side than on the left (27.99 mm vs. 25.87 mm, P=0.031). No statistically significant difference in EAC length was observed among the different age groups ( P>0.05). Furthermore, no statistically significant differences in EAC curvature were found regarding gender, side, or age group (all P>0.05). Conclusion:The HRCT-based 3D reconstruction technique enables the establishment of a rapid and effective automated workflow for extracting the central curve of the EAC and systematically measuring its length and curvature. The data obtained provide a reference and methodological support for further research on anatomical variations of the human EAC and its potential clinical applications, such as the design of otological instruments or surgical planning.

Objective:To explore the association between oral health status, the lower respiratory tract microbiome, and the frequent acute exacerbation phenotype in chronic obstructive pulmonary disease (COPD).Methods:This cross-sectional study enrolled 39 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalized in the Department of Respiratory Medicine, Henan Provincial People′s Hospital between March 2021 and December 2022. Based on the number of hospitalization episodes for acute exacerbation in the past year, patients were divided into a frequent exacerbator group (≥2 times, n=28) and a non-frequent exacerbator group (<2 times, n=11). Bronchoalveolar lavage fluid (BALF) samples were collected from all subjects for metagenomic next-generation sequencing (mNGS). Oral health indicators and clinical data were also collected. Statistical analyses were performed using Spearman correlation analysis and multivariable Firth logistic regression analysis. Results:The frequent exacerbation group showed a significantly higher percentage of individuals with≥8 tooth loss compared to the non-frequent exacerbation group (96.4% vs 18.2%, P<0.001), a significantly younger age at first tooth loss in adulthood (53.96±7.30 years vs 62.10±5.80 years, P=0.003), and a significantly higher proportion of individuals who hardly brushed their teeth (50.00% vs 9.09%, P=0.038). The alpha-diversity indices of the lower respiratory tract microbiota were significantly lower in the frequent exacerbation group than in the non-frequent exacerbation group (all P<0.01). The relative abundances of Bacillota, Bacteroidota, Fusobacteriota, Streptococcus, Prevotella, Veillonella, Neisseria, Rothia, Prevotellamelaninogenica, Prevotellajejuni, Rothia mucilaginosa, Veillonella parvula, and Neisseria subflava were lower in the frequent exacerbation group (all P<0.05). In patients with AECOPD, the exacerbation frequency and the presence of ≥8 tooth loss were both negatively correlated with the Shannon index ( r=-0.854, P<0.001; r=-0.642, P<0.001, respectively). Further analysis revealed that Bacillota ( r=-0.862, P<0.001) and Streptococcus ( r=-0.814, P<0.001) were significantly negatively correlated with exacerbation frequency, while Pseudomonas was positively correlated with exacerbation frequency (all P<0.05). Bacillota ( r=0.369, P=0.021), Fusobacteriota ( r=0.368, P=0.021), and Veillonella ( r=0.379, P=0.017) were positively correlated with FEV 1% predicted. Multivariable Firth logistic regression analysis revealed that the first principal component of the microbial community ( OR=2.29, 95% CI: 1.20-11.07) and the loss of≥8 teeth ( OR=14.37, 95% CI: 1.42-482.51) were independent factors associated with frequent acute exacerbations. Conclusion:Frequent acute exacerbations of COPD are significant association with deteriorated oral health and dysbiosis of the lower respiratory tract microbiome, characterized by reduced alpha-diversity and depletion of commensal bacteria.

Objective:To evaluate the impact of self-crosslinked hyaluronic acid (SCH) gel on endometrium recovery after artificial abortion.Methods:A multicenter, prospective randomized controlled trial was conducted across 18 hospitals from December 2021 to February 2023, involving 382 women who underwent artificial abortion. Participants were randomly allocated to receive either treatment with SCH gel (SCH group) or no treatment (control group) in a 1∶1 ratio. The primary outcome was endometrium thickness in 14 to 18 days after the first postoperative menstruation. Secondary outcomes included changes in menstrual volume during the first postoperative menstruation, menstruation resumption within 6 postoperative weeks, time to menstruation resumption, duration of the first postoperative menstruation, and incidence of dysmenorrhea.Results:Baseline characteristics of participants were comparable between the two groups (all P>0.05), with 95.3% (182/191) in SCH group and 92.7% (177/191) in the control group completed the study. The postoperative endometrial thickness in SCH group was significantly greater than that in the control group [(9.78±3.15) vs (8.95±2.32) mm; P=0.005]. SCH group also had significantly fewer participants with reduced menstrual volume [23 cases (12.6%, 23/182) vs 31 cases (17.5%, 31/177); P=0.038]. Although SCH group experienced less dysmenorrhea during the first postoperative menstrual period, this difference was not statistically significant [28.5% (51/179) vs 37.1% (65/175); P=0.083]. Outcomes were similar between SCH group and the control group regarding the proportion of participants who resumed menstruation within 6 weeks postoperatively, time to menstruation resumption, and duration of the first postoperative menstruation ( P=0.792, 0.485, and 0.254, respectively). No serious adverse events were observed during the study period, and no adverse events were attributed to SCH gel treatment. Conclusion:The application of SCH gel after artificial abortion is safe and might aid in the recovery of the endometrium.

Objective To construct a stable synovial cell line MH7A from rheumatoid arthritis(RA)patients using lentiviral vectors that interfere with the expression of tumor necrosis factor receptor associated factor 2(TRAF2),and to study the role of TNF-α-TRAF2 signaling in MH7A abnormal proliferation.Methods Based on the design principles of human TRAF2 gene sequence and shRNA sequence,three pairs of TRAF2 shRNA interference se-quences were designed and synthesized.The primers were annealed by PCR,and a linear vector was obtained by double enzyme digestion PLKO.1-puro.The linearized vector was connected to the annealed primers through Solu-tion I,and the connected products were introduced into receptive cells.The plates were coated,and positive colo-nies were selected for sequencing.Three different recombinant plasmids of PLKO.1-TRAF2-shRNA lentivirus were constructed,and lentivirus packaging plasmids was used to package logarithmic growth phase HEK 293T cells.Vi-rus solution was collected to infect MH7A cells.At the same time,puromycin was used to screen MH7A stable transgenic strains with low TRAF2 expression.CCK-8 method,Western blot,and qPCR were used to detect the proliferation function of MH7A induced by TNF-α and low expression of TRAF2,as well as downstream signal TRAF2,P65 protein expression and mRNA levels.Results PLKO.1-TRAF2-shRNA(1),PLKO.1-TRAF2-shR-NA(2),and PLKO.1-TRAF2-shRNA(3)lentivirus vector plasmids and control group lentivirus vector plasmids PLKO.1-puro were successfully constructed.The three TRAF2-shRNA lentivirus vector plasmids and control group lentivirus vector plasmids PLKO.1-puro were respectively introduced into the lentivirus packaging plasmid of HEK 293T to obtain virus solution.After infecting MH7A cells with the virus solution,they were treated with puromycin(2.00 μ G/mL)screening and obtaining MH7A stable transgenic plants after 2 days.Through qPCR and Western blot results,it was found that the expression of TRAF2 mRNA and protein in PLKO.1-TRAF2-shRNA(1)MH7A stably transfected cells was significantly reduced compared to the negative control group.The results of CCK-8 and Western blot showed that after knocking down TRAF2 in MH7A,the proliferation of MH7A cells with low TRAF2 expression induced by TNF-α and the phosphorylation level of P65 were significantly reduced.Conclusion A sta-ble transgenic strain of PLKO.1-TRAF2-shRNA(1)MH7A cells was successfully constructed to investigate the role of TNF-α-TRAF2 signal activation in mediating abnormal proliferation of RA synovial cells.

Background Cognitive behavioral therapy(CBT)is a widely used and empirically supported psychotherapy method.In recent years,the localization of CBT related to culture has received increasing attention from Chinese scholars.However,there is still a lack of systematic research on the localization of CBT using idioms as materials.Objective To explore whether idioms reflect the mutual influence between the two core therapeutic elements of CBT(cognition and emotion)and to use them as CBT treatment tools among college students,so as to provide references for the localization of CBT.Methods Using the Xinhua Idiom Dictionary(second edition)published by the Commercial Press,a three-round manual screening method was used to select idioms that reflected the mutual influence between cognition and emotion in CBT.Based on the selected idioms,a survey questionnaire titled"survey on idiom understanding level"was developed.From August to October,2022,stratified sampling was conducted among college students from different majors and universities,and 815 valid questionnaires were obtained through the Questionnaire Star platform.By analyzing the understanding of each idiom among college students,idioms that could be used as CBT treatment tools were identified.Results In the Xinhua Idiom Dictionary(second edition),there were 13 idioms that reflected the influence of cognition on emotion and 5 idioms that reflected the influence of emotion on cognition.12 idioms could be used as CBT treatment tools,including 8 idioms that reflected the influence of cognition on emotion and 4 idioms that reflected the influence of emotion on cognition.Conclusion There may be idioms that reflect the mutual influence between the two core therapeutic elements of CBT(cognition and emotion)and these idioms can be attempted as a therapeutic tool for CBT among college students.