Rapamycin regulates osteogenic differentiation through Parkin-mediated mitophagy in rheumatoid arthritis.

Varying degrees of bone destruction and bone loss occur in the development of rheumatoid arthritis (RA). Nevertheless, the mechanism underlying osteoporosis in the development of RA is not completely elucidated. Recent evidence indicates that mitophagy may play a vital role in regulating the differentiation and function of preosteoblast. Parkin is associated with mitophagy and various inflammatory diseases, but the precise role of Parkin in the treatment of osteoporosis in RA is unclear. In the present study, we found that the abnormal bone metabolism of RA is related to the activation of the mechanistic targets of mTORC1 pathway, and chronic inflammation which regulates the differentiation of preosteoblast through mitophagy. In this study, we found that Parkin was upregulated, and the mitochondrion was damaged in tumor necrosis factor alpha (TNF-α) stimulated preosteoblasts. Rapamycin (RAPA, an mTORC1 pathway blocker) upregulation of Parkin-mediated mitophagy tends to attenuate mitochondrial impairment caused by TNF-α in preosteoblasts. Theexperimentinvivo demonstrated that the combination therapy with TNF-α neutralizing antibody and RAPA significantly reduced osteoporosis in AIA mice. Drug inhibition of this pathway can be a potential treatment for osteoporosis in patients with RA.

Erratum: A Single-Center Study of a Resin Inlay Dental Implant-Fixed Prosthesis for Closing Proximal Contact Loss in 89 Patients Who Underwent 3-Year Follow-Up.

The authors informed the journal that Figure 4A was incorrectly a duplicate of Figure 5A. The correct version of Figure 4 is below. Reference: Qiyue Chen, Yong Shi, Zhaoqiang Zhang, Guangbao Song. A Single-Center Study of a Resin Inlay Dental Implant-Fixed Prosthesis for Closing Proximal Contact Loss in 89 Patients Who Underwent 3-Year Follow-Up. Med Sci Monit, 2021; 27: e933809. DOI: 10.12659/MSM.933809.

A Single-Center Study of a Resin Inlay Dental Implant-Fixed Prosthesis for Closing Proximal Contact Loss in 89 Patients Who Underwent 3-Year Follow-Up.

BACKGROUND Proximal contact loss (PCL) is very common between implant-fixed prostheses (IFPs) and adjacent teeth and leads to a high incidence of food impaction. Our aim was to determine if the mesio-distal adjustable (MDA) crown prostheses introduced in this study could easily establish new contacts intraorally without the intervention of prostheses retrieval. MATERIAL AND METHODS The MDA crown requires casting in the inlay framework at the proximal contact area. If PCL occurred, the resin in the inlay framework could be easily removed and refilled chairside. This single-center prospective study aimed to investigate the use of a resin inlay dental implant-fixed prosthesis for the closing proximal contact loss in 93 patients who were recruited from April 2017 to December 2017. Four patients dropped out during the 3-year follow-up; therefore, 89 patients were included. The effect of this technique was assessed by the implant mucosal status and follow-up investigations of food impaction. RESULTS PCL occurred in 29.21% (26 prostheses) of the IFPs. The PCL rate at the mesial contact surfaces (n=24, 26.97%) was significantly higher than that at the distal contact surfaces (n=5, 8.33%) (P<0.01); however, the incidence of PCL was greater at adjacent teeth with significant bone resorption (P=0.00). After readjusting the resin inlay and closing the clearance, implant mucosal status and food impaction were significantly reduced (P<0.01). CONCLUSIONS The findings of this study showed that use of the MDA crown for closing PCL was time-saving and effective with satisfactory results at 3-year follow-up.

Ezrin regulates synovial angiogenesis in rheumatoid arthritis through YAP and Akt signalling.

This study aimed to investigate the role and regulatory mechanisms of Ezrin in synovial vessels in rheumatoid arthritis (RA). Synovial tissues were obtained from people with osteoarthritis people and patients with RA patients. We also used an antigen-induced arthritis (AIA) mice model by using Freund's adjuvant injections. Ezrin expression was analysed by immunofluorescence and immunohistochemical staining in synovial vessels of patients with RA and AIA mice. We investigated the role of Ezrin on vascular endothelial cells and its regulatory mechanism in vivo and in vitro by adenoviral transfection technology. Our results suggest a role for the Ezrin protein in proliferation, migration and angiogenesis of vascular endothelial cells in RA. We also demonstrate that Ezrin plays an important role in vascular endothelial cell migration and tube formation through regulation of the Hippo-yes-associated protein 1 (YAP) pathway. YAP, as a key protein, can further regulate the activity of PI3K/Akt signalling pathway in vascular endothelial cells. In AIA mice experiments, we observed that the inhibition of Ezrin or of its downstream YAP pathway can affect synovial angiogenesis and may lead to progression of RA. In conclusion, Ezrin plays an important role in angiogenesis in the RA synovium by regulating YAP nuclear translocation and interacting with the PI3K/Akt signalling pathway.

Evaluation of the effect of concentrated growth factor in guided bone regeneration in maxillary anterior tooth defects / 口腔疾病防治

Objective@#To investigate the clinical effect of concentrated growth factor (CGF) applied in guided bone regeneration (GBR) for severe bone deficiency in the anterior maxilla.@*Methods @#Forty patients with bone defects in the anterior maxilla were chosen to be treated with GBR, 20 patients were treated with CGF applied in GBR as the observation group, and the other 20 patients were treated only with GBR as the control group. The evaluation of wound healing was performed after the operation, and bone augmentation was evaluated half a year after the operation.@*Results@#The first-stage healing rate of soft tissue wounds in the observation group was 100% and 75% in the control group, and the primary healing rate in the observation group was better than that in the control group (P=0.017). The changes in bone width of the observation group were （3.70 ± 0.28） mm, and those of the control group were （2.96 ± 0.16） mm. The bone augmentation in the observation group was higher than that in the control group (P=0.000). @*Conclusion@#CGF applied in GBR has a good effect on bone augmentation for severe bone deficiency in the anterior maxilla.

Detection of MSX1 gene mutations in patients with congenital tooth loss in Van der Woude syndrome / 口腔疾病防治

Objective@#To explore the relationship between MSX1 gene detection and tooth loss in a Van der Woude syndrome (VWS) family @* Methods @# DNA was extracted from the venous blood of 2 patients with dental hy⁃podontia in the 9th family of Van der Woude syndrome (VWS) families and 62 controls with complete dentition. Primers were designed for the MSXl gene. The coding regions of exons 1 and 2 of the MSX1 gene were amplified by PCR. The purified products of exons 1 and 2 of the MSX1 gene were sequenced and analyzed by sequence alignment @*Results@#The ivs2+68 C>T polymorphism in the MSX1 gene was found in the VWS9 members with tooth loss, and the VWS pa⁃tients with IRF6 gene mutations had increased tooth loss@* Conclusion@#Congenital tooth loss in the patients with con⁃genital missing teeth in VWS family 9 may be related to the ivs2 + 68 C> T polymorphism of the MSX1 gene.

Aberrant histone modification and inflammatory cytokine production of peripheral CD4+ T cells in patients with oral lichen planus.

BACKGROUNDS: To investigate alterations in histone modification and histone deacetylases (HDACs) in patients with oral lichen planus (OLP), and to evaluate correlations with inflammatory cytokine production. METHODS: Global histone H3/H4 acetylation and HDAC activity in CD4+ T cells from 23 patients with OLP and 10 healthy control subjects were examined using spectrophotometry. The mRNA levels of eight members of four classes of HDAC genes were measured by real-time quantitative polymerase chain reaction. Forty cytokines involved in inflammation were examined with a cytokine array. The correlation between histone modification and cytokine production was analyzed. RESULTS: Global histone H3 hypo-acetylation was observed in OLP patients. Patients with OLP had significantly higher HDACs activity,and higher HDAC6 and HDAC7 mRNA level compared with the controls. Of the 40 cytokines in the cytokine array, eight were significantly increased in OLP patients: interleukin (IL)-4, IL-8, IL-1ra, tumor necrosis factor receptor II (TNFR II), macrophage inflammatory protein 1b (MIP-1b), fibrosis-associated tissue inhibitors of metalloproteinase 1 (TIMP)-1, monocyte chemotactic protein 1 (MCP-1), and eotaxin-2. In the OLP group, the acetylation level of histone H3 was negatively correlated with IL-4 and MCP-1 production, and the expression of HDAC6 mRNA was positively correlated with MCP-1 production. In the non-erosive subgroup, acetylation of histone H3 was negatively correlated with IL-4, IL-16, and TIMP-2 production. In the erosive OLP subgroup, the expression of HDAC7 mRNA was positively correlated with MIP-1a production. CONCLUSION: Aberrant histone modification of CD4+ T cells in peripheral blood could occur in OLP patients, and possibly affects inflammatory cytokine production.

[Effect of preoperative anxiety level on postoperative pain sensation in patients receiving implant denture for partial edentulism].

OBJECTIVE: To explore the effect of preoperative anxiety level on postoperative pain sensation in partially edentulous patients undergoing surgery for implant denture. METHODS: Eighty partially edentulous patients receiving implant denture were examined for preoperative anxiety level using State Trait Anxiety Inventory (STAI) and Modified Dental Anxiety Scale (MDAS) questionnaires before implantation surgery. The Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Questionnaire were used to assess the pain sensation in patients immediately after the operation. The correlations of preoperative state anxiety, trait anxiety, and dental anxiety with postoperative VAS score were analyzed. According to the assessment results of STAI, the patients were divided into little or no (score range 20-37) anxiety group (L group), moderate (38-44) anxiety group (M group), and high (45-80) anxiety group (H group) to analyze the effect of state anxiety and trait anxiety levels on postoperative pain sensation. RESULTS: Significantly positive correlations were found between preoperative state anxiety, trait anxiety and dental anxiety among the patients (P<0.01). Postoperative VAS score was positively correlated with trait anxiety score (P<0.01) and differed significantly between different trait anxiety groups (P<0.01). Compared with the patients in M and L groups, those in H group showed a significantly higher VAS score after the operation (P<0.05). CONCLUSION: The preoperative trait anxiety level is associated with postoperative pain sensation in partially edentulous patients receiving implant denture, suggesting the necessity of preoperative anxiety intervention in clinical practice.

[Use of recombinant human beta-defensin-3 to evaluate the effect of adhesion of Candida albicans on the surface of soft lining material].

PURPOSE: To evaluate the effectiveness of recombinant human beta-defensin-3 (rHBD3) on reduction of Candida albicans from the surface of soft lining materials. METHODS: Specimens made of soft lining materials, which had been contaminated with C. albicans, were immersed in 25 µg/mL rHBD3 and 5.25% sodium hypochlorite (a positive control) for 5, 10, 30 and 60 min. The results were analyzed statistically with SPSS 10.0 software package. Confocal laser scanning microscopy(CLSM) of biofilm-associated C. albicans were treated with rHBD3 in different times. RESULTS: The results confirmed that an immersion time of 30 min or higher yielded a good disinfection effect, both for the experimental group and the positive control. A large number of pathogenic bacteria were killed and the cells were stained red by SYTO9/PI after 30 min. CONCLUSIONS: It is possible that soft lining materials immersed in rHBD3 solution that possesses antifungal activity may be clinically protective.

[Osteoblastic early attachment onto the surface of bioadhesive peptide modified pure titanium].

OBJECTIVE: To investigate the long-term integrity and the biological function of interface between the bioadhesive peptide modified implant surface and peri-implant tissue. METHODS: A short bioadhesive peptide containing Glycine-Tyrosine-Arginine-Glycine-Asparticacid-Serine (GYRGDS) sequence was immobilized onto the titanium implant surface by means of sol-gel coating technique and self-assembled monolayers (SAM). The chemical composition and organic functional groups on the titanium surfaces were characterized using XPS (X-ray photoelectron spectroscopy) and FTIR (Fourier transform infrared spectrometer). The adhesive strength and stability of osteoblasts on various implant surfaces were compared under flow condition. RESULTS: The results showed that alkali/hot water aging treatment could apparently improve the content of -OH functional groups of titanium surface. The chemical reactive Ti-O-Ti bonding at the surface of titanium played a vital role in inducing the formation of organosilane SAM. GYRGDS peptide can be covalently grafted onto the surface of titanium by SAM technique. The resistance of freshly adherent osteoblasts to detachment by flow was shear time dependent. When the four groups were compared under the same flow stress condition (2.05 Pa) at three specific time spans (30 min, 1 h, 2 h), the cells retention rates in GYRGDS-grafted groups were 93.0%, 54.4%, 34.4% respectively and were much higher than those in non-coated groups. CONCLUSIONS: It was suggested that GYRGDS might have positive effects on maintaining stability and adherence of cells onto the substrates under flow condition.

[Clinical application of maxillary sinus lift with Summers osteotome].

OBJECTIVE: To introduce and evaluate the procedure and the effect of maxillary sinus lift with closed technique by Summers osteotome, bone grafting and simultaneous implant placement. METHODS: 66 cases with severely resorbed alveolar bone in maxillary posterior region received sinus lift with Summers osteotome, simultaneously bone grafting and implants placement. The final restoration was finished at 6 months postoperatively. RESULTS: The operation procedure were eventless in the 66 cases, the sinus floor were elevated by 2-5 mm, three-dimensional reconstruction of the CT scan pictures showed the smooth dome profile of the lifting sites and no signs of laceration on the membrane, and there were no maxillary antritis after operation. After 6 months, no significantly bone graft resorption and good osseointegration were noticed in X-ray imaging. The final restoration was finished at this time. 12-24 months after the restoration, all implants inserted were remain, the hard and soft tissue were healthy, prosthesis were stable and functioned. X-ray showed good osseointegration in the lifting sites, the vertical resorption around the implants were less than 1 mm. CONCLUSION: With properly use of Summers osteotome, scraps of the bone in the implant sockets can be pushed into the sinus, these autogenous bone scraps were in favor of the osseogenesis and the sinus floor can be easily elevated by the method with very infrequent complications. It enlarged indication of dental implants and avoided operation of harvesting autogenous bone in other site. The method is simple and valuable to clinical application.

[Clinical study of autotransplanting of impacted anterior tooth and premolar].

OBJECTIVE: To evaluate the effect of autotransplantation of impacted anterior tooth and premolar. METHODS: Nineteen teeth of 19 patients were made autotransplantation. Fifteen impacted anterior teeth were transplanted to their normal positions. Four premolars were transplanted into missing anterior spaces. Four weeks after surgical procedure, root canal therapy was underwent. Clinical and radiographic examintation of 19 transplanted teeth were carried out after 18-months to 5-years. RESULTS: Nineteen teeth were stable with no sign of inflammatory resorption or periapical lesion. CONCLUSION: Autotransplantation may be a better treatment method to impacted tooth and missing anterior when they can't be treated by orthodontic method.

[Dental implants in patients with Type 2 diabetes mellitus: a clinical study.].

PURPOSE: The oral rehabilitation by dental implants in patients with diabetes remains a controversial issue.The aim of this study was to investigate the clinical results of implantation in patients with Type 2 diabetes mellitus. METHODS: This study group consisted of 21 patients with Type 2 diabetes mellitus who received 52 implants. RESULTS: There were 5 failures.The success rate was 90.4% with a follow up period of 12 to 37 months. CONCLUSIONS: The clinical outcome of dental implants in selected group of patients with well-controlled type 2 diabetes mellitus is satisfying and encouraging.Further investigations and clinical trials over a longer period of time are needed to determine the long-term survival of implants in diverse of patients with diabetes mellitus.

[Clinical application of maxillary sinus augmentation, bone graft and simultaneously placement of implant with trephine bur].

OBJECTIVE: To introduce and evaluate the procedure and the effect of localized management of sinus floor (LMSF), bone graft and simultaneous implant placement with trephine bur in maxillary posterior region. METHODS: 24 patients without enough alveolar bone height received LMSF, bone grafting and implants placement were carried out simultaneously.The autogenous bone were harvested by trephine bur in situ. Patients were followed up after 1 week, 1, 3 and 6 month. RESULTS: There was no implant loose or lost and maxillary antritis. 6 months postoperatively, bone graft reformed to new bone seen in X-ray films, sinus floors were augmented and reached the requirements of dental implants. The implant osseointegrated tightly with new bone which was satisfactory to second-step prosthesis after implant placement of 6 months later. CONCLUSIONS: The method enlarges the indication of dental implants and avoids operation of harvesting autogenous bone in other site. It is simple and valuable to clinical application.

[Single-tooth replacement in the aesthetic zone with immediate provisionalization].

OBJECTIVE: To investigate the clinical results of immediate loading of a single anterior implant. METHODS: 8 Frialit-2 implants were placed into anterior sites. Provisional prosthesis were placed at the time of fixture placement. RESULTS: No fixture has been lost since the immediate restoration was delivered, the minimum being 7 months and the maximum 14 months. CONCLUSION: Clinical studies on the placement of immediate restoration in anterior implant have revealed predictable results.

[Clinical application of maxillary endossenous implant with edentulous ridge expansion technique].

OBJECTIVE: To evaluate the application and the effect of edentulous ridge expansion(ERE) technique in maxillary endossenous implant placement. METHODS: 49 patients with maxillary alveolar ridge atrophy received edentulous ridge expansion using condenser. In order to be similar to natural root, dental implants were selected and placed to tooth missed sites according to the requirements of aesthetics, function and dimension. RESULTS: 49 patients with atrophied alveolar ridge received 86 implants. The labio-lingual width augmented from 3.3 to 5.4 mm and the alveolar ridge height from 2 to 7 mm 6 months after operation. The implants osseintergrated tightly with alveolar bone and second-step prosthesis was performed 6 months after implant placement. CONCLUSION: The edentulous ridge expansion technique can meet the requirements of aesthetics and function and is applicable to endossenous implant placement in maxilla. The method is simple and valuable to clinical application.