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

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.

Purpose: The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods: An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results: Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

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.

The end of the COVID-19 infection peak in 2022 prompts a backlog of cardiovascular surgical patients to gradually return to the hospital, resulting in a surge in cardiovascular surgeries. However, against the backdrop of the COVID-19 pandemic, the clinical practice of cardiovascular surgery faces many problems. Therefore, organized by Beijing Anzhen Hospital, experts in cardiovascular surgery and related fields have formulated hospital expert experience on perioperative treatment principles of cardiovascular surgery for patients infected with COVID-19. This article summarizes the clinical decision-making of patients requiring cardiovascular surgery after COVID-19 infection, and advises on the corresponding recommendations according to the existing evidence-based medical evidence as well as the actual clinical practice experience of relevant experts. The main content of the article includes special requirements for cardiovascular surgical treatment indications in patients with COVID-19 infection, selection of surgical timing, special requirements of preoperative, intraoperative and postoperative management, etc., which aims to provide COVID-19-infected patients with guidance on rational decision-making when receiving cardiovascular surgery.

PURPOSE: A large number of studies have suggested the practicability and predictability of immediate implant function, but few studies have reported marginal bone level changes during sequential loading periods. The purpose of this study was to evaluate the marginal bone remodeling of immediately loaded self-tapping implants both at each time point and during each loading period between two time points. MATERIALS AND METHODS: The patients included in this retrospective study were treated with immediately loaded NobelSpeedy Replace implants between August 2008 and July 2009. Differences in the marginal bone level (MBL) at each time point and the marginal bone level change (ΔMBL) between two time points were analyzed with Bonferroni correction (P < .05). RESULTS: Overall, 24 patients (mean age, 47.3 ± 12.8 years) with 42 immediately loaded implants and a median follow-up of 6.5 years (IQR, 67.8 months) were included. The cumulative survival rate after 10 - 12 years was 95.2%. Continuous but slow marginal bone loss was observed during long-term follow-up. MBL at both 7.5 years and 11 years was significantly lower than that at loading, 6 months, 2 years and 4 years (P < .05). No bone loss difference was found in any period before 4 years of follow up (P > .05). The loading period of 4 years to 7.5 years showed the largest ΔMBL compared to those of other time periods (P < .05). CONCLUSION Slight bone loss occurred continuously, and more radical changes of marginal bone can be observed during the period of 4-7.5 years. Thus, long-term effective follow-up of immediately loaded implants is needed.

Due to the COVID-19 pandemic, the teaching of Biopharmaceutical Engineering course was carried out online and completed with satisfactory outcomes. In order to improve the efficiency of online teaching, ensure the substantive equivalence between online and offline teaching and achieve effective teaching, this article summarized the exploration and practical experience of online teaching, taking the Biopharmaceutical Engineering course as an example. This includes analysis of learner characteristics, selection of online teaching platform, development of teaching resources, optimization of teaching contents, BOPPPS teaching method-based design of teaching structure, and reflection of effective teaching. This paper is expected to provide a useful reference for online teaching.
Humans ; Biological Products ; Pandemics ; COVID-19

Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer therapy. Among vascular coagulation agents, the extracellular domain of coagulation-inducing protein tissue factor, truncated tissue factor (tTF), is the most widely used. Since the truncated protein exhibits no coagulation activity and is rapidly cleared in the circulation, free tTF cannot be used for cancer treatment on its own but must be combined with other moieties. We here developed a novel, tumor-specific tTF delivery system through coupling tTF with the DNA aptamer, AS1411, which selectively binds to nucleolin receptors overexpressing on the surface of tumor vascular endothelial cells and is specifically cytotoxic to target cells. Systemic administration of the tTF-AS1411 conjugates into tumor-bearing animals induced intravascular thrombosis solely in tumors, thus reducing tumor blood supply and inducing tumor necrosis without apparent side effects. This conjugate represents a uniquely attractive candidate for the clinical translation of vessel occlusion agent for cancer therapy.

To seek convenient and effective method for reconstruction of edentulous jaw, Maló and his colleagues developed All-on-Four implant immediate-function concept. The principle of All-on-Four is to support the full-arch prosthesis by 4 implants and to achieve immediate loading after surgery. Its advantages include avoiding additional bone grafting, evading critical anatomical structures and immediate prosthesis. In recent years, All-on-Four technique has been widely utilized in clinical practice as a viable approach for edentulous patients. With the auxiliary of guided surgery and biomechanical researches, All-on-Four has achieved predictable clinical results. In this paper, the development, investigation of biomechanics and main points of surgery and prosthesis of All-on-Four were briefly reviewed.