[Comfortable initial periodontal therapy: step by step].

With the transition of the medical model from the traditional biomedical model to the biopsychosocial one, there is a growing trend and requirement for oral operations that prioritize comfort, pain management, minimally invasive techniques, and visualization. Consequently, demands for comfortable dental treatments among individuals are increasing. However, initial periodontal therapy is often accompanied by pain, and patients' reactions to pain range from nervousness to dental fear, such as irritability, hyperventilation, even nausea, vomiting, and refusal to cooperate, which make the implementation of initial periodontal therapy difficult or even impossible. This article will focus on three key steps: firstly, the preparation of the clinic, the acquisition of patients' trust and the implementation of preventive sedation before treatment; secondly, the use of comfort operation and nursing, psychological intervention measures, local anesthesia, and sedation techniques during treatment; thirdly, the health education and follow-up after treatment. By addressing these aspects, we aim to clarify how to perform comfortable initial periodontal therapy step by step.

[Inhibitory effect of downregulating G protein-coupled receptor class C group 5 member A expression on lipopolysaccharide-induced inflammatory response in human gingival fibroblasts].

Objective: To clarify the effect and the mechanism of G protein-coupled receptor class C group 5 member A (GPRC5A) on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (GFs), thus to provide a foundation for delving into the role of G protein coupled receptor (GPCR) in periodontitis. Methods: Gingival tissue samples were collected from 3 individuals periodontally healthy (health group) and 3 patients with periodontitis (periodontitis group) in Shandong Stomatological Hospital from December 2022 to February 2023. The expressions of GPRC5A of the two groups were detected by immunohistochemistry staining. GFs used in this study were isolated from a portion of gingiva for the extraction of impacted teeth in School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University from December 2022 to February 2023. GFs were isolated with enzymic digestion and transfected with 30, 50 and 80 µmol/L small interfering RNA-GPRC5A (siGPRC5A) or small interfering RNA-negative control (siNC), regarded as the experimental group and the negative control one, respectively. The silencing efficiency of siGPRC5A was evaluated by real-time fluorescence quantitative PCR (RT-qPCR). Experiments were then conducted using these cells which were divided into four groups of negative control (NC), LPS, siGPRC5A+LPS and siGPRC5A. The mRNA and protein levels of GPRC5A in GFs under 1 mg/L LPS-induced GFs inflammatory state were evaluated by RT-qPCR and Western blotting analysis after GPRC5A knockdown. RT-qPCR was used to detect the gene expression levels of the inflammatory cytokines in GFs induced by LPS, namely, interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, prostaglandin endoperoxide synthase 2 (PTGS2) after GPRC5A knockdown. Western blotting analysis and immunofluorescence staining were used to further investigate the activation of nuclear factor-kappa B (NF-κB) signaling pathway. Results: Immunohistochemistry staining showed that the expression of GPRC5A in gingival tissues of periodontitis group (0.132±0.006) increased compared with that in periodontally healthy group (0.036±0.019) (t=8.24, P=0.001). Meanwhile, RT-qPCR results showed that the gene expression levels of GPRC5A at different time point (2, 6, 12, 24 h) in LPS-induced GFs (0.026±0.002, 0.042±0.005, 0.004±0.000, 0.016±0.000) were upregulated compared with those in the NC group (0.004±0.000, 0.004±0.000, 0.002±0.000, 0.007±0.000) (all P<0.001), respectively, and peaked at 6 h. The 50 µmol/L group displayed the most significant decrease in siGPRC5A expression (31.16±3.29) compared with that of the siNC group (100.00±4.88) (F=297.98, P<0.001). The results of RT-qPCR and Western blotting analysis showed that siGPRC5A (0.27±0.03, 0.71±0.00) suppressed the expressions of GPRC5A at both gene and protein levels, while LPS (1.30±0.10, 1.43±0.03) was able to promote the expressions of GPRC5A compared with those of the NC group (1.00±0.01, 1.00±0.00)(all P<0.001). The siGPRC5A+LPS group (0.39±0.03, 1.06±0.16) also inhibited the increase of GPRC5A at both gene and protein levels induced by LPS (1.30±0.10, 1.43±0.03) (F=208.38, P<0.001; F=42.04, P<0.001). RT-qPCR results showed that the expressions of IL-8, IL-1ß, IL-6, TNF-α, and PTGS2 at the gene level in LPS group were highly increased compared with those in the NC group (all P<0.001). siGPRC5A significantly suppressed LPS-induced expressions of these inflammatory cytokines in GFs (all P<0.001). Western blotting analysis showed that the levels of p65 and IκBα protein phosphorylation in the LPS group were highly increased compared with those in the NC group, and siGPRC5A could effectively suppressed LPS-induced protein phosphorylation (all P<0.01). Furthermore, immunofluorescence staining showed that NF-κB p65 in the control group was mainly concentrated in the cytoplasm, and partially translocated to the nucleus under the stimulation of LPS. siGPRC5A was able to inhibit LPS-induced intranuclear translocation of p65 to a certain extent. Conclusions: GPRC5A expression was upregulated in periodontitis, and GPRC5A knockdown inhibited LPS-induced inflammation. Moreover, GPRC5A played a role in inflammation regulation by interacting with NF-κB signaling pathway.

[Review on the development of periodontology in China].

Chinese Journal of Stomatology has gone through 70 years of ups and downs, witnessing the development of periodontics in China from a faltering start to twists and turns, and finally innovative development. This article aims to review the periodontology-related papers published in the Chinese Journal of Stomatology. Based on the characteristics of the times, they are summarized into five stages: staggering start, forced stagnation, vigorous development, standardized innovation, and disciplinary integration. Researches on periodontal diseases in China initially focused on learning and reference, gradually caught up with the international level, and finally created in-depth insights and innovations. Eventually, Chinese periodontology has formed a research system with Chinese characteristics and achieved substantial achievements in clinical diagnosis and treatment, basic research, periodontal medicine, and disciplinary integration. Although the current status of Chinese periodontology still lags behind that of developed countries, these representative studies demonstrate the unremitting efforts and hard work of periodontists for generations, laying a solid foundation for the innovation and development of periodontology in our country.

[The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study].

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

[Research progress and application prospect of stem cells in inflamed dental tissues on periodontal bone regeneration].

Tissue engineering has become a research hotspot regarding periodontal bone regeneration in recent years. Generally, stem cells used in periodontal tissue engineering are derived from healthy dental tissues, while restricted due to the strict indication of tooth extraction and limited sources. Stem cells in inflamed dental tissues mainly derive from inflamed pulp, periapical and periodontal tissues. Stem cells in inflamed dental tissues are abundant and retain most of the basic characteristics of stem cell compared with the ones derived from healthy dental tissues, which can be a promising source of stem cells for periodontal bone regeneration. In this review, we summarize the current application and prospect of stem cells in inflamed dental tissues on periodontal bone regeneration, and then discuss their feasibility as seed cells, in order to provide a reference for future research and clinical application of stem cells in inflamed dental tissues.

[Advances in the periodontal surgical flaps techniques to preserve gingival papilla].

Papilla preservation in periodontal surgery is not only beneficial to maintain postoperative aesthetics and good oral hygiene but also contributes to obtaining good periodontal regeneration outcomes. Various periodontal flaps have been designed to preserve the gingival papilla, which constitutes the clinical basis for periodontal open flap debridement and periodontal regeneration surgery. A comprehensive understanding of their design purpose, indications, and technical key points will help clinicians to choose the optimal surgical plan, and thus improve the clinician's treatment levels, and obtain good clinical outcomes. Therefore, this article aims to introduce the design background, indications, and technical key points of various surgical flaps, such as papilla preservation technique, modified papilla preservation technique, simplified papilla preservation flap, etc.

[Introduction and interpretation of the European Federation of Periodontology S3 level clinical practice guideline for treatment of periodontitis].

2018 international classification of periodontal and implant diseases relates the classifications with the approaches of prevention and treatment based on the stages and grades of disease. European Federation of Periodontology (EFP) evaluated the available evidences following the methodological guidance of the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), and published the EFP S3 level clinical practice guideline for the treatment of stage Ⅰ-Ⅲ and Ⅳ periodontitis in 2020 and 2022, respectively. The present manuscript gives introduction and interpretation based on the EFP S3 level clinical practice guideline and Chinese national conditions. On the base of the diagnostic key points of staging and grading, it introduces in detail the step treatment procedures of stageⅠ-Ⅲ periodontitis as well as the multi-disciplinary treatment procedures of stage Ⅳ periodontitis, compares the similarities and differences between the step and phase procedures, and then proposes a strategy for determining the recall interval more suitable for Chinese clinicians. The present manuscript aims to help dentists to learn and grasp the key points more quickly and accurately on the clinical application of the guideline and to assist them in making the optimal treatment plans after judging and evaluating the specific clinical circumstances, so as to maximize the chances of favorable outcome.

[Study on the dynamic changes of oral microbiota in type 2 diabetes patients with periodontitis after initial periodontal therapy].

Objectives: To clarify the effect of initial periodontal therapy on the dynamic changes of oral (saliva, dorsal tongue and subgingival plaque) microbiota in periodontitis patients with or without type 2 diabetes mellitus (T2DM). Methods: A total of 14 patients with chronic periodontitis (CP group) and 14 CP patients with T2DM (CP-T2DM group) were included from Department of Periodontology, School and Hospital of Stomatology,Cheeloo College of Medicine, Shandong University. The microbial samples were collected from saliva, dorsal tongue and subgingival plaque of first molars at baseline, 1.5 and 3 months after initial periodontal therapy, and were detected by 16S rRNA (V3-V4 region) gene sequencing. The sequencing data were analyzed to obtain microbial distribution and community structure information. The same professional periodontist evaluated the periodontal status of patients according to periodontitis detection indices before and after initial periodontal therapy. Meanwhile, patients' blood samples were collected and related metabolic indices were evaluated. Results: After initial periodontal therapy, the glycosylated hemoglobin levels [(7.46±1.69)%] in CP-T2DM group were significantly improved than that at baseline [(7.65±1.34)%] (t=0.52,P=0.610). The probing depth of the sampling sites [CP group: (2.94±0.46) mm, CP-T2DM group: (2.95±0.35) mm] and bleeding index (CP group: 1.91±0.42, CP-T2DM group: 1.67±0.49) at 3 months after treatment were significantly decreased than the probing depth [CP group: (3.99±0.77) mm, CP-T2DM group: (3.80±0.76) mm] (F=25.61, P<0.001; F=17.63, P<0.001) and bleeding index (CP group: 3.03±0.52, CP-T2DM group: 2.54±0.65) (F=28.43, P<0.001; F=20.21, P<0.001) at baseline. The flora analysis showed that the α and ß diversity indices of the same sites in the CP and CP-T2DM groups did not change significantly before and after the initial therapy, but the bacterial abundance at each site changed. There were commonalities and differences in the microbial composition of each site in the CP and CP-T2DM groups. Among them, the relative abundance of Proteobacteria in saliva and dorsal tongue samples of the two groups after treatment was basically consistent with the change trend in the subgingival plaque microbes. In the subgingival plaque of the CP group, the relative abundance of Proteobacteria showed a gradual increase with the prolongation of initial periodontal therapy; while in the CP-T2DM group, it showed a trend of first increase and then decrease. Syntrophy, Dethiosulfate, Methanobacteriaceae and TG5 in CP and CP-T2DM groups were all significantly dominant bacteria in subgingival plaque at baseline (P<0.05). Moreover, in the CP-T2DM group Spirochetes also showed a significant advantage. At 1.5 months after treatment, Rhizobacteria, Alcaligenes, Comamomons, Delftia, Blautella, etc. were dominant in subgingival plaque (P<0.05). Firmicutes, Clostridia/Clostridiales, Enterococci and Ruminococci showed significant differences at 3 months (P<0.05). Conclusions: Plaques in saliva and tongue dorsal could reflect the effects of initial periodontal therapy on the dynamic changes of microorganisms to a certain extent. CP and CP-T2DM patients had differences in microbial composition and responses to initial periodontal therapy.

[Research advances in the interaction of periodontitis and psoriasis].

Periodontitis is a common chronic infectious oral disease, which is characterized by gingival inflammation,pocket formation, alveolar bone loss and tooth mobility. Psoriasis is a common chronic inflammatory skin disease, whose pathological features in skin lesions are excessive proliferation of epidermal cells, parakeratosis of the derma, and the infiltration of inflammatory cells. Both periodontitis and psoriasis are closely related to the interleukin(IL)-23/helper T cell 17(Th17)/IL-17 axis in their immunopathological mechanisms. The risk factors of psoriasis include smoking, vitamin D deficiency, obesity, emotional stress, etc, of which most factors are also common risk factors of periodontitis. The present article reviews the research advances in the interaction of the two diseases and their possible common mechanisms from three aspects, i.e. clinical study, IL-23/Th17/IL-17 pathway and common risk factors, which may be helpful to provide new ideas for clinical diagnosis and treatment.

[Wnt3a promotes osteogenic differentiation of periodontal ligament stem cell and regeneration of alveolar bone in experimental periodontitis].

Objective: To explore the effects of Wnt3a on the proliferation, migration and osteogenic differentiation of periodontal ligament stem cell (PDLSC) and to identify the role of Wnt3a in alveolar bone regeneration in mouse experimental periodontitis. Methods: The experiments were conducted by stimulating PDLSC using Wnt3a of 5 different concentrations (0, 20, 100, 200, 500 µg/L) respectively. Cell proliferation was detected by cell-counting assay, cell migration was evaluated by Transwell assay and the expressions of osteogenic related genes collagen Ⅰ (Col-Ⅰ), runt-related transcription factor 2 (Runx2) were examined by real-time quantitative PCR (RT-qPCR). Poly lactic-co-glycolic acid (PLGA)-Wnt3a-hyaluronic acid (HA) hydrogel was injected locally into the gingival sulcus of mice with experimental periodontitis. After 1, 2, 4, and 8 weeks of hydrogel injection, samples of maxillary alveolar bone were obtained. Micro-CT, HE staining and immunohistochemical staining of osteogenesis related markers, such as alkaline phosphatase (ALP), Runx2, osteocalcin (OCN), were used to evaluate alveolar bone regeneration. Results: After 10 d of culture, Wnt3a with concentrations of 20-500 µg/L significantly promoted the proliferation (P<0.01) and the migration (P<0.01) of PDLSC. After 21 d of culture, the expression levels of Col-Ⅰ mRNA were 0.96±0.27, 1.90±0.47, 2.18±0.24, 2.32±0.15 and 1.99±0.43 in 5 concentration groups respectively, and the expression levels of Runx2 mRNA were 1.08±0.15, 3.19±0.17, 6.19±0.28, 9.19±0.41 and 5.55±0.06, respectively. Both expressions had significant statistical differences compared with the negative control group (P<0.05). At 1, 2, 4, and 8 weeks, the Wnt3a hydrogel group had less distance [(497.3±18.2), (455.7±12.5), (401.0±8.5), (362.3±15.5) µm] from the cemento-enamel junction to alveolar bone crest compared with the periodontitis group [(710.3±10.2), (614.0±16.4), (564.3±12.5), (502.3±6.8) µm] (P<0.01) and weaker periodontal inflammation. Immunohistochemical results showed that the expression levels of bone-related proteins of ALP (0.72±0.01), Runx2 (0.77±0.03) and OCN (0.72±0.07) in the Wnt3a hydrogel group were increased compared with the periodontitis group (P<0.01). Conclusions: Wnt3a might promote the proliferation, migration and osteogenic differentiation of PDLSC and the alveolar bone regeneration.

First-principles study of the elastic and thermodynamic properties of CaSiO(3) perovskite.

The thermodynamic and elastic properties of CaSiO(3) perovskite are investigated at high pressures and temperatures using the plane wave pseudopotential method within the local density approximation. The athermal elastic moduli of CaSiO(3) perovskite are calculated as a function of pressure up to 200 GPa. The calculated results are in excellent agreement with available experimental data at high pressure, and compare favourably with other pseudopotential predictions over the pressure regime studied. It is also found that the elastic anisotropy drops rapidly with the increase of pressure initially, and then decreases more slowly at higher pressures. The thermodynamic properties of CaSiO(3) perovskite are predicted using the quasi-harmonic Debye model for the first time; the heat capacity and the thermal expansion coefficient agree with the observed values at ambient conditions and the other calculations at high pressures and temperatures.

[The effect on angiogenesis in guided tissue regeneration procedure using expanded polytetrafluoroethyene membranes in dogs].

OBJECTIVE: To observe the effect on angiogenesis in guided tissue regeneration procedures in which the barrier membranes were designed to be left for different time. METHODS: Periodontal defects were created on buccal side of mesial root of mandibular third and fourth premolar in dogs. An experimental polytetrafluoroethyene (ePTFE) membrane was adapted to leave in place for 2, 3, 4 and 8 weeks,respectively. In the control defects(right mandibular second premolar), no membrane was used. At the end of 8 weeks,all the animals were perfused with a combined solution of carbon black ink and 10% formalin solution and killed. 500 microm thick specimens were processed. Descriptive histology was carried out,evaluating angiogenesis in area of new supraalveolar and gingival flaps. RESULTS: Histologic analysis demonstrated that new vascular meshworks were built between the gingival flap and new connective tissue in the wound in 2-week,3-week and 4-week groups.However, in 8-week group, the number of supraalveolar blood vessels were fewer than that in other groups.But vascular rebuilt in gingival flap in 8-week group had come to normal. CONCLUSION: The existance of nonresorbable membrane could affect the rebuilt of supraalveolar vascular meshwork, but it had no significant effect on the blood circulation in gingival flap. The revascularization between gingival flap and the new connective tissue was not significantly influenced after the membranes were removed from 2 to 4 weeks' placement.

[Effects of bFGF on biological characteristics of cells derived from periodontium].

OBJECTIVE: To observe effects of basic fibroblast growth factor on the biological characteristics of cultured human gingival,periodontal ligament fibroblasts and human alveolar bone cells, such as proliferation, alkaline phosphatase activity, protein synthesis and the formation of mineralized nodules. METHODS: Using cell culture technique, MTT colorimetric assay, ALP activity assay, Commasie brilliant blue staining and Dahl McGec-Russell's alizarin red stain for calcium. RESULTS: bFGF enhanced the proliferative responses of the three types of cells. In contrast, bFGF inhabited the induction of alkaline phosphatase activity, protein synthesis and the mineralized nodule formation by PDLF and ABC. CONCLUSION: bFGF can enhance cell proliferation while inhibit cytodifferentiation, thus accelerating periodontal regeneration.