Complement C3 plays a critical role in periodontitis. However, its source, role and underlying mechanisms remain unclear. In our study, by analyzing single-cell sequencing data from mouse model of periodontitis, we identified that C3 is primarily derived from periodontal fibroblasts. Subsequently, we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis. C3ar^-/- mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice, characterized by mild gingival tissue damage and reduced alveolar bone loss. This reduction was associated with decreased production of pro-inflammatory mediators and reduced osteoclast infiltration in the periodontal tissues. Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation. Finally, by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis, we found that the results observed in mice were consistent with human data. Therefore, our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis, driven by macrophage M1 polarization and osteoclast differentiation. These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
Animals ; Osteoclasts/cytology* ; Periodontitis/metabolism* ; Cell Differentiation ; Mice ; Fibroblasts/metabolism* ; Macrophages ; Disease Models, Animal ; Complement C3/metabolism* ; Humans ; Disease Progression ; Mice, Inbred C57BL ; Male ; Mice, Knockout

ObjectiveTo investigate the developmental characteristics of gross motor skills and executive functions, and the correlation between them in school-age children with attention deficit hyperactivity disorder (ADHD). MethodsFrom November, 2020 to May, 2021, 90 children with ADHD were recruited from Peking University Sixth Hospital and Beijing Haidian Wanquan Primary School, and other 90 children with normal development from this primary school were recruited matched their age and gender. Gross motor skills were assessed with the Test of Gross Motor Development in Children, Third Edition (TGMD-3), and inhibitory control, working memory, and cognitive flexibility were assessed with Stroop Color Words Test (SCWT), Rey-Osterrich Complex Figure Test (ROCFT) and Trail Making Test (TMT), respectively. ResultsThe TGMD-3 score was significantly lower in children with ADHD than in normal children (t = -6.275, P < 0.001), while the test results of SCWT, ROCFT and TMT were worse (|t| ≥ 1.986, P ≤ 0.05). The TGMD-3 score of children with ADHD was negatively correlated with the word sense reaction time (r = -0.261), the number of word sense errors (r = -0.404) and the number of color errors (r = -0.326) (P < 0.05), positively correlated with the delayed structural memory scores (r = 0.228) (P < 0.05), and negatively correlated with the TMT-A reaction time (r = -0.255), the number of TMT-A errors (r = -0.329), TMT-B reaction time (r = -0.214) and the number of TMT-B errors (r = -0.474) (P < 0.05). Stratified linear regression analyses showed that the TGMD-3 score of children with ADHD was significant only in predicting test results for inhibitory control and cognitive flexibility (P < 0.05), with explanations of 8.7% and 22.5%, respectively. ConclusionDevelopments of both gross motor skills and executive function delay in children with ADHD, and there is a relation between them, especially the level of gross motor skills relating to the developments of inhibitory control and cognitive flexibility.

Objective:To explore the effect of acute exercise on the executive function in patients with atten-tion deficit hyperactivity disorder(ADHD),and to provide a theoretical basis for the exercise intervention of ADHD.Methods:Experimental studies on the effect of acute exercise on executive function in patients with ADHD published up to 21 April 2023 were searched from PubMed,Web of Science,Cochrane Library,Embase,CNKI,Wanfang,and other data platforms.Results:A total of 15 studies were included,and 515 patients with ADHD were included.The results of meta-analysis showed that a single exercise could improve inhibitory control(SMD=0.36,95％CI=0.17-0.55,P＜0.05)and cognitive flexibility(SMD=0.40,95％CI=0.10-0.69,P＜0.05)in pa-tients with ADHD.The results of subgroup analysis showed that in terms of the age of the participants,a single ex-ercise could only improve inhibitory control and cognitive flexibility in children and adolescents with ADHD(SMD=0.36,0.43,Ps＜0.05),but not in adult patients with ADHD(SMD=0.34,0.14,Ps＞0.05).In terms of exer-cise regimen,only a single exercise with moderate and high intensity,≤ 20 minutes,and open motor skills could simultaneously improve inhibitory control(SMD=0.47,0.51,0.47,Ps＜0.05)and cognitive flexibility(SMD=0.86,0.65,0.86,Ps＜0.05)in patients with ADHD.Conclusion:Acute exercise could improve inhibitory control and cognitive flexibility in children and adolescents with ADHD,but has no significant effect on working memory and executive function in adult patients.

Objective To explore the impact of exercise intervention on the reading abilities of chil-dren with Chinese developmental dyslexia(CDD).Methods Twenty-seven CDD children were recruited from patients of Peking University Sixth Hospital,and randomly divided into a CDD exercise interven-tion group of 14 and a CDD control group of 13.Another 14 age-matched normal children were select-ed into a normal control group.All groups kept daily physical activities in school,while the CDD ex-ercise intervention group additionally underwent 8-week individualized gross and fine motor interven-tion.The literacy,reading fluency and reading comprehension of all groups were evaluated by using"Elementary School Students'Literacy Test and Evaluation Scale",one-minute word reading and ele-mentary school students'reading ability assessment.Results Before the intervention,there were no sig-nificant differences between the exercise intervention and control groups in the literacy level,reading fluency,and reading comprehension(P>0.05),which were all significantly lower than the normal con-trol group(P<0.05).However,after the intervention,significant improvement was observed in the aver-age literacy level,reading fluency,and reading comprehension of the CDD exercise intervention group,and the literacy and reading fluency of the CDD control group,as well as the average literacy level and reading comprehension of the normal control group.Moreover,there were no significant differ-ences between the CDD exercise intervention and control groups in the average literacy level and read-ing fluency score(P>0.05),both significantly lower than the normal control group(P<0.05).Mean-while,the reading comprehension score of the CDD exercise intervention group was significantly higher than the CDD control group(P<0.05),but significantly lower than the normal control group(P<0.05).Conclusion Eight-week targeted gross and fine motor intervention can effectively improve reading abili-ty of DD children,especially their reading comprehension.

ObjectiveTo explore the characteristics of fine motor skills of school-age children with attention deficit hyperactivity disorder (ADHD) in different sexes. MethodsFrom April, 2021 to April, 2023, 66 ADHD children from grades one to four in Beijing Haidian Wanquan Primary School were screened by psychiatrists, and other 69 ADHD children were recruited from hospitals and patient groups of WeChat, accounting to 135 ADHD children. Meanwhile, a total of 135 typically developed (TD) children matched with sex and age (< 0.5 year) were recruited from the same primary school as controls. They were assessed with Movement Assessment Battery for Children (MABC-2) four subtests of manual dexterit. ResultsAfter controlling age, the subtest scores and the total score of fine motor of MABC-2 were less in ADHD boys and girls than in the TD boys and girls (P < 0.05). The main effect of sex was significant on the subtest scores and the total score of fine motor for ADHD children (F > 5.133, P < 0.05), and they were less in the boy than in the girls (P < 0.05). ConclusionThe development of fine motor delays in school-aged ADHD children, especially for the boys.

Objective : To investigate the effects of angiopoietin 4 (ANGPT4) on the odontogenic differentiation of human dental pulp stem cells. Methods : This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Human premolars were fixed, decalcified, dehydrated, embedded, and sectioned. Immunofluorescence staining was used to observe the expression and localization of ANGPT4. Human dental pulp stem cells (hDPSCs) were isolated and cultured in vitro. The growth state and morphology of hDPSCs were observed under an inverted phase contrast microscope. The expression of cell surface-related molecular markers was detected by flow cytometry. Alkaline phosphatase and alizarin red S staining were used to detect the odontogenic differentiation potential of hDPSCs. Oil-red O staining was used to detect the adipogenic differentiation potential of hDPSCs. RNA was extracted from hDPSCs at different time points after odontogenic induction, and RT-qPCR was used to analyze the mRNA expression of ANGPT4 and odontogenic-related genes during the odontogenic differentiation of hDPSCs in vitro. siRNA gene silencing technology was used to silence the expression of ANGPT4 in hDPSCs, and the silencing efficiency was detected by RT-qPCR and Western Blot. After silencing ANGPT4 in hDPSCs for 24 h, odontogenic induction was performed. Alkaline phosphatase and alizarin red S staining were performed on the 7th and 14th of induction to detect the odontogenic differentiation ability of hDPSCs after silencing ANGPT4 Results : Immunofluorescence staining of human premolars showed that ANGPT4 was expressed in odontoblasts and sub-odontoblastic cell-rich zone. hDPSCs were in good condition after 14 days of isolation and culture. Under the microscope, multiple cell colonies were observed, and the cell morphology was uniform and long spindle-shaped. The results of flow cytometry showed that hDPSCs expressed mesenchymal stem cell markers CD105 (90.42%) and CD90 (97.15%), but did not express hematopoietic cell markers CD45 (0.01%) and CD34 (0.08%). After odontogenic and adipogenic induction of hDPSCs, alkaline phosphatase staining, alizarin red S staining and oil red O staining were positive. The results of RT-qPCR after the odontogenic induction of hDPSCs showed that ANGPT4 was highly expressed on the 5th, 7th, 11th and 14th days of differentiation of hDPSCs (P<0.05), with the highest expression level on the 5th day. After hDPSCs were transfected with si-ANGPT4, the expression of ANGPT4 mRNA and protein was significantly down-regulated (P<0.05). The results of alkaline phosphatase staining showed that ALP staining intensity and area in the si-ANGPT4 group were significantly lower than those in the negative control. Alizarin red S staining showed that the formation of calcium nodules in the si-ANGPT4 group was significantly lower than that in the negative control. Conclusion ANGPT4 was expressed in odontoblasts and sub-odontoblastic cell-rich zone of human premolars. ANGPT4 may be a factor to promote the odontogenic differentiation of hDPSCs.

Objective To observe the electromyography characteristics of children's handwriting with attention deficit hyperactivity disorder(ADHD),and explore its electrophysiological mechanism,so as to provide an objective basis for developing non-pharmacological treatment for such children.Methods Between September 2021 and April 2022,29 ADHD children were recruited from an ordinary public primary school and the psychiatric clinic of a class-3 grade-A hospital in Beijing.Among them,25 were boys and 4 were girls,with an average age of 8.21±1.78 years.Meanwhile,23 male and 5 fe-male healthy counterparts were selected with the age gap no more than 6 months.The Delsys wireless surface EMG system was used to collect the electromyographic signals of the abductor pollicis breve,the first dorsal interosseous muscle,the flexor radial carpi motor and the extensor finger muscles dur-ing their writing tasks such as tracing trajectories,writing Arabic numerals 0-9,26 small and capital English letters,Chinese characters one to ten and"Yong".The percentage of the averaged electromyog-raphy(AEMG)of a muscle in the sum value of all measured muscles,and the coefficient of differ-ence were selected to evaluate the muscle contribution rate and the consistency of exertion,respective-ly.Moreover,the independent sample t-test was employed to compare the two different groups with the significance set at α=0.05.Results There was a significant difference in the muscle contribution of abductor pollicis breve and first dorsal interosseous muscles when writing Arabic numerals and that of abductor pollicis breve muscles when writing Chinese characters between ADHD children(27.29%,25.58%and 27.53%)and their healthy counterparts(42.87%,19.96%and 37.13%)(P<0.05).Most muscle differentiation coefficients of ADHD children were higher than 100%,with that of the domi-nant hand radial wrist flexor muscle reaching 270%in the trajectory tracing task.Conclusion Accord-ing to the characteristics of EMG signals,school-age ADHD children show an immature writing pat-tern,including poor stability of writing-related muscles,insufficient control of small finger muscle groups,poor control of hand coordination,and insufficient muscle inhibition of non-dominant hand.It is recommended to conduct the electromyoelectric assessment of handwriting movements in ADHD chil-dren,so as to carry out targeted intervention at an early stage.

Recent studies find that the expression of hepatoma-derived growth factor (HDGF) is closely correlated with the tumorigenesis,progression,metastasis,therapy and prognosis of various malignancies.Though the mechanism of the interaction of HDGF and tumors is still unclear,the research of HDGF serving as a tumor marker in malignancies and a new target for tumor treatment has become a hotspot in the research of tumor.

Objective:To evaluate the effectiveness and safety of anticoagulant therapy with rivaroxaban in atrial fibrillation( AF) pa-tients after radiofrequency catheter ablation( RFCA) . Methods:A retrospective analysis was performed in the study. Totally 141 AF pa-tients with RFCA in our hospital were enrolled from January 2014 to October 2015. The patients were divided into rivaroxaban group(70 patients)and warfarin group (71 patients). In rivaroxaban group,rivaroxaban(10 mg, po,qd)was given for at least 3 months after RFCA. In warfarin group,low molecular heparin (100 IU·kg-1,ih) was given before RFCA, and standard dose of warfarin (3-5 mg,po,qd) was given for at least 3 months by adjusting the INR within the range of 2. 0-3. 0 after RFCA as bridging therapy. The death rate, throm-boem bolism events and bleeding events between the groups were evaluated and companed groups. Results: There were no significant differences in baseline characteristics between the groups except the diastolic pressure. There were no significant differences in the death and thromboembolism events(transient cerebral ischemia , ischemic encephalopathy, 2/70 vs 4/71,P>0. 05)between the groups. There were no TIMI major bleeding events in both groups. There were no significant differences in minor bleeding events between the groups (3/70 vs 4/71,P>0. 05). Conclusion: Compared with those of warfarin,the effectiveness and safety of rivaroxaban show the similar effect in AF patients after RFCA. Rivaroxaban can be safely and effectively used in AF patients with low or middle risk of thromboembo-lism after RFCA.