[Locally delivered macrolides as an adjunct to non-surgical periodontal treatment of chronic periodontitis: a meta analysis].

PURPOSE: The present meta analysis was designed to determine the effects of macrolides group of antibiotics as local drug delivery agents to scaling and root planing (SRP), compared with SRP alone or plus placebo. METHODS: Electronic and manual literature searches were conducted to select randomized controlled trials (RCTs) comparing SRP + macrolides versus SRP alone using the following databases: PubMed, Cochrane Library, Science Direct, EMbase, CNKI, Wanfang database and VIP data until August 2018. Two reviewers independently extracted the data and evaluated the methodological quality of the included studies. RevMan 5.3 was applied for meta analysis. RESULTS: Seven papers were obtained, which included 439 patients with chronic periodontitis.Meta analysis showed that in the two groups, the changes in probing depth（PD）[MD=0.77, 95%CI(0.48-1.05), P<0.00001], clinical attachment loss（CAL）[MD=0.74, 95%CI(0.39-1.10), P<0.0001],plaque index（PI）[MD=0.30, 95% CI(0.17-0.43), P<0.00001]，modified sulcus bleeding index (mSBI)[MD=0.23, 95%CI(0.15-0.32), P<0.00001]at 3 month and 6 month of PD[MD=1.15, 95%CI(0.41-1.89), P=0.002] were significantly different, the difference of CAL[MD=0.92, 95%CI(0.43-1.40), P=0.0002], PI[MD=0.51, 95%CI(0.07-0.95), P=0.02] and mSBI[MD=0.18, 95%CI(0.07-0.29), P=0.002] was also significant (P<0.05). CONCLUSIONS: SRP combined with local macrolides adjuvant treatment for chronic periodontitis is effective in short-term observation.

Prevalence and Years Lived with Disability for Dental Caries among Children Aged 0-14 Years in China, 1990-2016.

The estimate of dental caries among Chinese children at the microscale level using standard methodology remains unclear. In this study, we assessed and analyzed the disease burden of childhood dental caries in China by extracting data from the Global Burden of Disease, Injuries, and Risk Factors Study 2016 (GBD 2016). In 2016, the number of cases, prevalence, years lived with disability (YLD), and age-standardized YLD rate of dental caries was 93.0 million, 43.0%, 32,200 person years, and 14.8 per 100,000, respectively. Across 33 provincial units, the disease burden was highest in Hubei (YLD rate 28.6 per 100,000), lowest in Macao (9.1 per 100,000), while geographical clustering was not observed. Compared with 1990, the prevalence in 2016 decreased from 46.8% to 43.0%, and the YLD rate decreased from 16.5 per 100,000 to 14.8 per 100,000. Given the slight decrease in dental caries burden, the prevalence and disease burden remained high among Chinese children. Strategies for addressing the spatial inequity of childhood dental caries require geographical targeting.

Stromal Cell-Derived Factor-1α Alleviates Calcium-Sensing Receptor Activation-Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced Cell Apoptosis in Rat Free Flaps.

Surgical flaps are frequently affected by ischemia/reperfusion (I/R) injury. Calcium-sensing receptor (CaSR) and stromal cell-derived factor-1α (SDF-1α) are closely associated with myocardial I/R injury. This study was performed to evaluate the feasibility of applying SDF-1α to counteract CaSR activation-mediated I/R injury in ischemic free flaps. Free flaps that underwent ischemia for 3 h were equally randomized into five groups: CaCl2, NPS2143 + CaCl2, SDF-1α + CaCl2, AMD3100 + SDF-1α + CaCl2, and normal saline. The free flaps were harvested to evaluate flap necrosis and neovascularization after 2 h or 7 d of reperfusion. p-CaSR/CaSR was extensively expressed in vascular endothelial cells of free flaps after I/R injury, and activation of the SDF-1α/CXCR4 axis and NPS2143 could reduce the expression of cleaved caspase-3, caspase-9, FAS, Cyt-c, and Bax and increase Bcl-2 expression; the opposite was true after CaSR activation. Interestingly, initiation of the SDF-1α/CXCR4 axis might abrogate CaSR activation-induced I/R injury through enhancement of microvessel density. In conclusion, CaSR might become a novel therapeutic target of free flaps affected by I/R injury. Activation of the SDF-1α/CXCR4 axis and NPS2143 could counteract CaSR activation-mediated I/R injury and promote free flap survival through inhibition of caspase-3/caspase-9-related cell apoptosis and enhancement of neovascularization.

[p38 MAPK pathway mediated BMP9-induced osteogenetic differentiation of hPDLSCs].

PURPOSE: To determine the effect of p38 MAPK signaling pathway on BMP9-induced osteogenetic differentiation of human periodontal ligament stem cells( hPDLSCs)． METHODS： hPDLSCs were collected in vitro, and adenovirus vectors were used to infect hPDLSCs; then the activity and staining of alkaline phosphatase(ALP) were detected ,the expression of osteopontin (OPN) and osteocalcin(OCN) were detected by qPCR ，and the calcium nodule deposition was used to analyse the ability of BMP9-induced hPDLSCs osteogenetic differentiation. Phosphorylation of p38 and MKK3/6 was detected after hPDLSCs was intervened with Ad-BMP9 and SB203580 ( inhibitor of p38 MAPK signaling pathway) for 36 h respectively for the effect of the signaling pathway on osteogenic differentiation． SPSS16.0 software package was used for statistical analysis. RESULTS: Under the action of Ad-BMP9, the activity of ALP, the levels of osteopontin and osteocalcin genes were significantly higher than the control group (P<0.01). Staining of ALP and the calcium nodule deposition were consistent with the activity of ALP, the levels of osteopontin and osteocalcin. Western blot demonstrated that the expression of p-p38 and p-MKK3/6 was increased significantly. After adding SB203580, the expression of ALP, OPN and OCN was decreased significantly (P<0.01),and the calcium mineral deposits were also decreased. CONCLUSIONS: During hPDLSCs differentiation, BMP9 can induce osteogenesis, and MKK3/6-p38-MAPK pathway was involved in the osteogenesis and had positive regulation for osteogenesis of hPDLSCs.

[Platelet-rich plasma combined with demineralized freeze-dried bone allografts for periodontal regeneration in the treatment of periodontal defects: a meta-analysis].

PURPOSE: The aim of this meta analysis was to assess the influence of platelet-rich plasma (PRP)combined with demineralized freeze-dried bone allografts(DFDBA) on regeneration of periodontal periodontal defects by means of evaluating clinical and radiographic outcomes in prospective human clinical trials. METHODS: The following databases such as PubMed, The Cochrane Library, EMbase, CNKI, Wanfang data and VIP data were searched on computer from inception to December, 2016. According to the inclusion and exclusion criteria, two reviewers independently extracted the data，assessed the methodological quality of the included studies. RevMan 5.2 was applied for meta analysis. RESULTS: Six papers were obtained reviewed which included 205 periodontal bone defect sites. Six articles showed that there was no significant difference in probing depth decrease between PRP combined with DFDBA and PRP or DFBDA group[MD=0.35, 95%CI（-0.09，0.79), P=0.12], but there was significant difference in clinical attachment loss increase between the two groups［MD= 0.68，95%CI（0.41，0.94），P<0.00001]. Three articles were included for evaluating bone filling, there was significant difference in the distance from the cemento-enamel junction(CEJ) to the vertical bone defect(BD)(CEJ-BD)[MD=0.71，95%CI（0.46，0.95），P<0.00001]between the two groups; there was also significant difference in the distance from the alveolar crest to the vertical bone defect(AC-BD)[MD=0.64，95%CI（0.41，0.87)，P<0.00001]between the two groups. but there was no significant difference in the distance from the cemento-enamel junction(CEJ)to the alveolar crest (AC)(CEJ-AC)[MD=0.03，95%CI（-0.10，0.16），P=0.68] between the two groups. CONCLUSIONS: Within the limitations of this meta analysis, PRP combined with DFDBA is superior to PRP or DFDBA alone in clinical attachment loss and bone filling ,but there was no significant difference in probing depth. However, given the limited sample size and quantity of included studies, the above findings still need to be further proved by conducting more high-quality and large-scale RCTs.

[Effect of low-intensity pulsed ultrasound combined with triamcinolone acetonide on oral mucosal ulcer healing in syrian hamster].

PURPOSE: To evaluate the effect of low-intensity pulsed ultrasound（LIPUS） combined with triamcinolone acetonide on oral mucosal ulcer in syrian hamster in several ways, including healing time, contents of superoxide dismutase（SOD）and malondialdehyde (MDA). METHODS: Sixty syrian hamsters were randomly divided into 5 groups, including a baseline group (containing a normal baseline group and a model baseline group, n=6) and 4 experimental groups (LIPUS processing and drug use group, LIPUS group, drug group and a normal control group without any processing, n=12). Four experimental groups and model baseline group were given oxygen free radicals to model the oral mucosal ulcer. At 24 h after the last treatment, the healing time of ulcer, content of SOD and MDA were compared between each group. SPSS 20.0 software package was used for statistical analysis. RESULTS: Compared with LIPUS group,drug group and control group, the healing time of oral mucosal ulcer in LIPUS and drug combined group was shortened. At 24 h after the last treatment, the activity of SOD showed that the LIPUS and drug combined group[(2.32±0.30) U/mgprot] were significantly higher than the model baseline group[(1.48±0.29) U/mgprot], the LIPUS group[(1.83±0.15) U/mgprot], the drug group[(1.76±0.25) U/mgprot] and control group[(1.71±0.18) U/mgprot] (P<0.05). The results of MDA content showed that the LIPUS and drug combined group [(8.17±0.21) nmol/mgprot] were significantly lower than the model baseline group[(9.41±0.22) nmol/mgprot], the LIPUS group[(9.00±0.44) nmol/mgprot], the drug group [(9.04±0.43) nmol/mgprot] and control group[(9.03±0.46) nmol/mgprot] (P<0.05). After oral mucosal ulcer healing, the activity of SOD and MDA showed that the LIPUS and drug combined group, the LIPUS group, the drug group and control group were not significantly different from the normal baseline group (P>0.05). CONCLUSIONS: Low-intensity pulsed ultrasound combined with triamcinolone acetonide can effectively improve the activity of SOD and reduce the contents of MDA in ulcerated tissues, and therefore accelerate the process of ulcer healing．.

[Clinical significance of calcitonin gene-related peptide level before and after treatment in patients with chronic periodontitis].

PURPOSE: To explore the clinical significance of calcitonin gene-related peptide (CGRP) levels in patients with chronic periodontitis before and after treatment, and to detect the calcitonin gene-related peptide content in human venous blood. METHODS: Thirty healthy controls and thirty patients with mild, moderate, severe periodontitis were enrolled from August 2014 to June 2015.CGRP level in the patients' peripheral blood was detected by ELISA. Three months after periodontal treatment, CGRP level in mild, moderate, severe periodontitis patients' peripheral blood was re-examined by ELISA. Then the correlation between calcitonin gene-related peptide and inflammation of chronic periodontitis was analyzed with SPSS 22.0 software package. RESULTS: The content of CGRP in healthy controls was significantly higher than that in patients with periodontitis. With the aggravation of periodontal inflammation, blood level of CGRP decreased gradually, and the lowest was in patients with severe periodontitis (P<0.01). Three months after periodontal treatment, CGRP content was significantly higher compared with that before treatment (P<0.05), but no significant difference was found in patients with different degree of periodontitis (P>0.05). CONCLUSIONS: The level of CGRP in venous blood decreased with the increasing severity of chronic periodontitis, and CGRP was negatively correlated with the degree of inflammation of chronic periodontitis. CGRP may be involved in the occurrence and development of chronic periodontitis. CGRP content in serum of patients with chronic periodontitis after treatment was significantly increased, CGRP may be used as the basis for clinical detection of chronic periodontitis.

Porphyromonas gingivalis lipopolysaccharide increases lipid accumulation by affecting CD36 and ATP-binding cassette transporter A1 in macrophages.

Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) promotes macrophage-derived foam cell formation, however, the mechanisms are not well established. In macrophages, lipid uptake is mediated by scavenger receptors including SR-A and CD36, while the cholesterol efflux is mediated by ATP-binding cassette transporter G1 (ABCG1), ABCA1 and SR-BI. We further investigated the mechanisms underlying the dysregulation by P. gingivalis LPS of these regulators resulting in the promotion of lipid accumulation in THP-1-derived macrophages. Our results showed that P. gingivalis LPS exacerbated lipid accumulation in oxidized low-density lipoprotein (oxLDL)-treated macrophages. However, cholesterol efflux was inhibited by P. gingivalis LPS in THP-1-derived macrophages. In oxLDL-untreated macrophages, P. gingivalis LPS treatment caused an increase in CD36 mRNA and protein levels, and a decrease in ABCA1 mRNA and protein levels, while having no effect on SR-A, SR-BI or ABCG1 expression. Upregulation of CD36 by P. gingivalis LPS resulted from activation of c-Jun/AP-1, and this was confirmed by the inhibition of increased CD36 expression after AP-1 inhibition using SP600125. However, the decreased protein stability of ABCA1 by P. gingivalis LPS was a result of increased calpain activity. Moreover, small hairpin RNA (shRNA) targeting heme oxygenase-1 (HO-1) augmented the P. gingivalis LPS-induced atherogenic effects on the expression of c-Jun/AP-1, CD36, ABCA1 and calpain activity. Accordingly, P. gingivalis LPS-regulated promotion of lipid accumulation in foam cells was also exacerbated by HO-1 shRNA. These results indicate that P. gingivalis LPS confers a exacerbation effect on the formation of foam cells by a novel HO-1-dependent mediation of cholesterol efflux and lipid accumulation in macrophages.

Tumor necrosis factor-α gene polymorphisms and risk of oral cancer: evidence from a meta-analysis.

Numerous studies have been conducted regarding association between TNF-α and oral cancer risk, but the results remain controversial. The present meta-analysis is performed to acquire a more precise estimation of relationships. Databases of Pubmed, the Cochrane library and the China National Knowledge Internet (CNKI) were retrieved until August 10, 2013. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated with fixed- or random-effect models. The heterogeneity assumption was assessed by I-squared test. Among the eight included case-control studies, all were focused on TNF-α-308G>A and four also concerned the TNF-α-238G>A polymorphism. It was found that oral cancer risk were significant decreased with the TNF-α-308G>A polymorphism in the additive genetic model (GG vs. AA, OR=0.19, 95% CI: [0.04, 1.00], P=0.05, I2=68.9%) and the dominant genetic model (GG+GA vs. AA, OR=0.22, 95% CI: [0.06, 0.82], P=0.03, I2=52.4%); however, no significant association was observed in allele contrast (G vs. A, OR=0.70, 95% CI: [0.23, 2.16], P=0.54, I2=95.9%) and recessive genetic models (GG vs. GA+AA, OR=0.72, 95% CI: [0.33, 1.57], P=0.41, I2=93.1%). For the TNF-α-238G>A polymorphism, significant associations with oral cancer risk were found in the allele contrast (G vs. A, OR=2.75, 95% CI: [1.25, 6.04], P=0.01, I2=0.0%) and recessive genetic models (GG vs. GA+AA, OR=2.23, 95%CI: [1.18, 4.23], P=0.01, I2=0.0%). Conclusively, this meta-analysis indicates that TNF-α polymorphisms may contribute to the risk of oral cancer. Allele G and the GG+GA genotype of TNF-α- 308G>A may decrease the risk of oral cancer, while allele G and the GG genotype of TNF-α-238G>A may cause an increase.

Hypoxia induces osteogenesis-related activities and expression of core binding factor α1 in mesenchymal stem cells.

Mesenchymal stem sells (MSCs) have received much attention in the field of bone tissue engineering due to their biological capability to differentiate into osteogenic lineage cells. Hypoxia-inducible factor 1alpha (HIF-1α) plays an important role in the MSC-related bone regeneration during hypoxia, while core binding factor alpha 1 (Cbfα1) is a transcription regulator that is involved in the chondrocyte differentiation and ossification. In the present study, we investigated the effects of hypoxia on biological capability of MSCs. MSCs were isolated from adult rabbit bone marrow, and were cultured in vitro under normoxia (air with 5% CO(2)) or hypoxia (5% CO(2) and 95% N(2)). The proliferation of MSCs, alkaline phosphatase (ALP) activity, and production of collagens type I and type III (Col I/III) were examined. The expression levels of HIF-1α and Cbfα1 were measured by real-time PCR and western blot analyses. We found that hypoxia significantly induced the proliferation of MSCs and increased ALP activity and the production of Col I/III. Moreover, hypoxia increased the expression of Cbfα1 mRNA after 12 h, whereas the expression of HIF-1α mRNA was increased after 1 h of hypoxia. Knockdown of HIF-1α expression with a small interfering RNA significantly increased the expression levels of Cbfα1 protein either under the normoxia or hypoxia condition. Our results indicate that hypoxia enhances MSCs to differentiate into osteogenic lineage cells and suggest that Cbfα1 may be negatively regulated by HIF-1α.