Patient and implant-related risk factors for implant failure of one-stage lateral sinus floor elevation: A 2- to 10-year retrospective study.

OBJECTIVES: This retrospective study aimed to evaluate the early and late implant failure rates of one-stage lateral sinus floor elevation (LSFE) and to identify the patient and implant-related risk factors associated with these failures. MATERIALS AND METHODS: All patients treated with one-stage LSFE from January 2014 to December 2021 were evaluated for inclusion. A total of 618 patients with 936 implants met the inclusion criteria. Clinical and radiographic information about patient and implants was collected. Univariate and multivariate Cox proportional hazards frailty regression models were performed to identify risk factors for early and late implant failure. RESULTS: The cumulative implant survival rate was 95.62% (95% CI 93.90%-97.68%), with 16 early implant failures and 25 late implant failures. The Cox analysis indicated that ≤3 mm residual bone height (RBH) was associated with a higher early failure rate. For late implant failure, smoking habit, ≤3 mm RBH, and certain implant brand were independent risk factors. Narrow sinus ostium, long infundibulum, and flat thickening of Schneiderian membrane might be non-independent risk factors for late implant failure. No significance was found in other variables, including age, periodontitis history, implant characteristics (position, diameter, length, protrusion length, marginal bone loss), surgeon experience, healing time, opposing dentition, and prosthesis. CONCLUSIONS: One-stage LSFE is a predictable treatment for patients with atrophic maxilla. ≤3 mm RBH increased the risk of early implant failure, while smoking habit, ≤3 mm RBH, and certain implant brand were independent risk factors for late implant failure.

Optogenetics in oral and craniofacial research. / å ‰é—ä¼ å­¦åœ¨å£è ”å’Œé¢Œé¢éƒ¨ç ”ç©¶ä¸­çš„åº”ç”¨.

Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control, noninvasiveness, and high efficiency. Genetically modified photosensory sensors are engineered into proteins to modulate conformational changes with light stimulation. Therefore, optogenetic techniques can provide new insights into oral biological processes at different levels, ranging from the subcellular and cellular levels to neural circuits and behavioral models. Here, we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research, focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo (orofacial movement, licking, eating, and drinking), such as channelrhodopsin (ChR), archaerhodopsin (Arch), and halorhodopsin from Natronomonas pharaonis (NpHR). We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial cellulitis. In addition, optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational studies. Although the scope of optogenetic tools is increasing, there are limited large animal experiments and clinical studies in dental research. Potential future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019 (COVID-19), studying oral bacterial biofilms, enhancing craniomaxillofacial and periodontal tissue regeneration, and elucidating the possible pathogenesis of dry sockets, xerostomia, and burning mouth syndrome.

The high-bone-mass phenotype of novel transgenic mice with LRP5 A241T mutation.

Gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) can cause high-bone-mass (HBM) phenotype, with 19 identified mutations so far. The A242T mutation in LRP5 has been found in 9 families, making it one of the most prevalent mutations. However, the correlation between the A242T mutation and HBM phenotype remains unverified in animal models. This study aimed to investigate the bone properties in a new transgenic mouse model carrying the LRP5 A241T missense mutation, equivalent to A242T in humans. Heterozygous Lrp5A241T mice were generated using CRISPR/Cas9 genome editing. Body weight increased with age from 4 to 16 weeks, higher in males than females, with no difference between Lrp5A241T mice and wild-type control. Micro-CT showed slightly longer femur and notably elevated trabecular bone mass of the femur and fifth lumbar spine with higher bone mineral density, bone volume fraction, and trabecular thickness in Lrp5A241T mice compared to wild-type mice. Additionally, increased cortical bone thickness and volume of the femur shaft and skull were observed in Lrp5A241T mice. Three-point bending tests of the tibia demonstrated enhanced bone strength properties in Lrp5A241T mice. Histomorphometry confirmed that the A241T mutation increased bone formation without affecting osteoblast number and reduced resorption activities in vivo. In vitro experiments indicated that the LRP5 A241T mutation enhanced osteogenic capacity of osteoblasts with upregulation of the Wnt signaling pathway, with no significant impact on the resorptive activity of osteoclasts. In summary, mice carrying the LRP5 A241T mutation displayed high bone mass and quality due to enhanced bone formation and reduced bone resorption in vivo, potentially mediated by the augmented osteogenic potential of osteoblasts. Continued investigation into the regulatory mechanisms of its bone metabolism and homeostasis may contribute to the advancement of novel therapeutic strategies for bone disorders.

In vitro and in vivo accuracy of autonomous robotic vs. fully guided static computer-assisted implant surgery.

OBJECTIVES: To assess the accuracy of autonomous robotic and fully guided static computer-assisted implant surgery (sCAIS) performed on models and patients. MATERIALS AND METHODS: This study was divided into in vitro and in vivo sections. In vitro, 80 operators were assigned to two groups randomly. Forty operators performed forty autonomous robotic implant (ARI group) surgeries and the remaining forty operators carried out forty fully guided sCAIS (FGI group) surgeries on maxillary models, respectively. Each operator placed an implant in one maxillary model. In vivo, 60 patients with 113 implants from 2019 to 2023 (ARI group: 32 patients, 58 implants; FGI group: 28 patients, 55 implants) receiving implant surgeries were incorporated in this retrospective research. The preoperative and postoperative cone beam computer tomographs (CBCTs) were utilized to estimate the linear deviations and angular deviations in two-dimensional (2D) and three-dimensional (3D) space. The Pearson's chi-square test, Shapiro-Wilk test, Student's t test, Mann-Whitney U test and mixed models were applied, and p <0.05 was considered statistically significant. RESULTS: In vitro, a total of 80 implants were enrolled and significant differences were found between the two groups (p < 0.001): The 3D deviation at the platform of ARI and FGI group was 0.58 ± 0.60 mm and 1.50 ± 1.46 mm, respectively, at the apex was 0.58 ± 0.60 mm and 1.78 ± 1.35 mm, respectively, and angle was 1.01 ± 0.87° and 2.93 ± 1.59°, respectively. Also, except for mesiodistal deviation at the implant platform, the rest linear and angular deviations in the ARI group were significantly lower than those in the FGI group in 2D space (p < 0.001). In vivo, a significantly lower mean of angular deviation (0.95 ± 0.50°, p < 0.001) and the linear deviation at both platform (0.45 ± 0.28 mm, p < 0.001) and apex (0.47 ± 0.28 mm, p < 0.001) were observed in ARI group when compared to the FGI group (4.31 ± 2.60°; 1.45 ± 1.27 mm; 1.77 ± 1.14 mm). CONCLUSIONS: The use of autonomous robotic technology showed significantly higher accuracy than the fully guided sCAIS.

Effect of mitophagy in the formation of osteomorphs derived from osteoclasts.

Osteoclasts are specialized multinucleated giant cells with unique bone-destroying capacities. A recent study revealed that osteoclasts undergo an alternative cell fate by dividing into daughter cells called osteomorphs. To date, no studies have focused on the mechanisms of osteoclast fission. In this study, we analyzed the alternative cell fate process in vitro and, herein, reported the high expression of mitophagy-related proteins during osteoclast fission. Mitophagy was further confirmed by the colocalization of mitochondria with lysosomes, as observed in fluorescence images and transmission electron microscopy. We investigated the role played by mitophagy in osteoclast fission via drug stimulation experiments. The results showed that mitophagy promoted osteoclast division, and inhibition of mitophagy induced osteoclast apoptosis. In summary, this study reveals the role played by mitophagy as the decisive link in osteoclasts' fate, providing a new therapeutic target and perspective for the clinical treatment of osteoclast-related diseases.

The association of work physical activity and recreational physical activity with periodontitis in the NHANES (2009-2014).

BACKGROUND: The aim of this study was to investigate the association between different types and intensity of physical activities (PA) and periodontitis in a nationally representative sample of adults in the United States. METHODS: The data of periodontal condition and PA of 10,714 individuals were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014 and the Global Physical Activity Questionnaire (GPAQ). The association between the prevalence of periodontitis and two PAs (work PA and recreational PA) was respectively analyzed and adjusted by uni- and multi-variable logistic regression models. The odd ratios (ORs), adjusted odd ratios (ORad ), and 95% confidence interval (95% CI) were calculated as the main outcome indicators. RESULTS: After adjusted by age, sex, race, poverty-income ratio (PIR), diabetes, smoking status, alcohol use, and floss frequency, moderate and vigorous work PAs were significantly correlated with higher odds of periodontitis (ORad  = 1.22, 95% CI = 1.02-1.46; ORad  = 1.40, 95% CI = 1.04-1.89, respectively) while moderate and vigorous recreational PAs were correlated with lower odds of periodontitis (ORad  = 0.81, 95% CI = 0.69-0.95; ORad  = 0.55, 95% CI = 0.43-0.71, respectively). CONCLUSIONS: Work PAs and recreational PAs have opposite associations on the prevalence of developing periodontitis and their aggravating or protective associations enhance with the increase of intensity.

A certain protective effect of vitamin D against dental caries in US children and youth: A cross-sectional study.

OBJECTIVES: Recent studies reported that evidence of the association between caries and vitamin D was inconclusive. We investigated the relationship between dental caries and serum vitamin D levels in US children and youth aged 5-19 years through the National Health and Nutrition Examination Survey (NHANES). The purpose of this study was to analyze the relations between serum 25-hydroxyvitamin-D [25(OH)D] level and dental caries in children and youth. METHODS: Data were collected from the NHANES dataset performed in 2011-2018. A total of 8896 subjects completed the examination was enrolled. Serum 25(OH)D was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). All teeth examined and caries assessment was conducted by licensed dentists. Statistical analyses included complex samples Chi-square tests, analysis of variance, logistic regression analyses, and restricted cubic splines conducted by R software. RESULTS: There was a nonlinear relation between dental caries and age in youth. Vitamin D showed a relatively stable protective effect when the concentration exceeded 60 nmol/L. There was a dose-effect relation that a 10 nmol/L increase in serum 25(OH)D concentrations was associated with a decreased caries odd by 10%. CONCLUSIONS: Our findings suggested that vitamin D sufficiency may be a protective factor for dental caries.

RNA-Seq-based transcriptomics analysis during the photodynamic therapy of primary cells in secondary hyperparathyroidism.

BACKGROUND: The aim of this study was to identify changes in gene expression before and after 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and to investigate the potential mechanism of 5-ALA-PDT based on ribonucleic acid sequencing (RNA-Seq) analysis. METHODS: Secondary hyperparathyroidism (SHPT) primary cells were isolated from surgically excised specimens and exposed to laser light. The transcription profiles of SHPT primary cells were identified through RNA-Seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to validate genes based on RNA-Seq results. RESULTS: In total, 1320 DEGs were identified, of which 1019 genes were upregulated and 301 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including TGF beta in extracellular matrix (ECM), negative regulation of triglyceride biosynthetic process, protein heterodimerization activity, systemic lupus erythematosus, ECM-receptor interaction, focal adhesion and protein digestion and absorption. Protein-protein interaction (PPI) network analyses identified potential heat shock protein (HSP) interactions among the DEGs. Eight HSP genes were also identified that were most likely involved in 5-ALA-PDT, which were further validated by RT-qPCR and western blotting. CONCLUSIONS: The findings of this descriptive study reveal changes in the transcriptome profile during 5-ALA-PDT, suggesting that gene expression and mutation, signaling pathways, and the molecular network are altered in SHPT primary cells. The above findings provide new insight for further studies on the mechanisms underlying 5-ALA-PDT in SHPT.

METTL3 depletion contributes to tumour progression and drug resistance via N6 methyladenosine-dependent mechanism in HR+HER2-breast cancer.

BACKGROUND: Chemotherapy is an important strategy for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+HER2-) breast cancer (BC), but this subtype has a low response rate to chemotherapy. Growing evidence indicates that N6-methyladenosine (m6A) is the most common RNA modification in eukaryotic cells and that methyltransferase-like 3 (METTL3) participates in tumour progression in several cancer types. Therefore, exploring the function of METTL3 in HR+HER2- BC initiation and development is still important. METHODS: mRNA and protein expression levels were analysed by quantitative real-time polymerase chain reaction and western blotting, respectively. Cell proliferation was detected by CCK-8 and colony formation assays. Cell cycle progression was assessed by flow cytometry. Cell migration and invasion were analysed by wound healing assays and transwell assays, respectively, and apoptosis was analysed by TUNEL assays. Finally, m6A modification was analysed by methylated RNA immunoprecipitation. RESULTS: Chemotherapy-induced downregulation of the m6A modification is regulated by METTL3 depletion in HR+HER2- BC. METTL3 knockdown in MCF-7/T47D cells decreased the drug sensitivity of HR+HER2- BC cells by promoting tumour proliferation and migration and inhibiting apoptosis. Mechanistically, CDKN1A is a downstream target of METTL3 that activates the AKT pathway and promotes epithelial-mesenchymal transformation (EMT). Moreover, a decrease in BAX expression was observed when m6A modification was inhibited with METTL3 knockdown, and apoptosis was inhibited by the reduction of caspase-3/-9/-8. CONCLUSION: METTL3 depletion promotes the proliferation and migration and decreases the drug sensitivity of HR+HER2- BC via regulation of the CDKN1A/EMT and m6A-BAX/caspase-9/-3/-8 signalling pathways, which suggests METTL3 played a tumour-suppressor role and it could be a potential biomarker for predicting the prognosis of patients with HR+HER2- BC.

Genetically modified cell spheroids for tissue engineering and regenerative medicine.

Cell spheroids offer cell-to-cell interactions and show advantages in survival rate and paracrine effect to solve clinical and biomedical inquiries ranging from tissue engineering and regenerative medicine to disease pathophysiology. Therefore, cell spheroids are ideal vehicles for gene delivery. Genetically modified spheroids can enhance specific gene expression to promote tissue regeneration. Gene deliveries to cell spheroids are via viral vectors or non-viral vectors. Some new technologies like CRISPR/Cas9 also have been used in genetically modified methods to deliver exogenous gene to the host chromosome. It has been shown that genetically modified cell spheroids had the potential to differentiate into bone, cartilage, vascular, nerve, cardiomyocytes, skin, and skeletal muscle as well as organs like the liver to replace the diseased organ in the animal and pre-clinical trials. This article reviews the recent articles about genetically modified spheroid cells and explains the fabrication, applications, development timeline, limitations, and future directions of genetically modified cell spheroid.

Maxillary sinus floor augmentation comparing removing versus retaining antral pseudocyst: A retrospective cohort study.

OBJECTIVES: To retrospectively compare multilevel volumetric changes in both hard and soft tissues between antral pseudocyst (AP) removal and retainment before maxillary sinus floor augmentation (MSFA) and immediate implant placement. MATERIAL AND METHODS: Twenty-six patients with 38 implants placed from 2016 to 2021 were included and divided according to a cohort design as follows: 13 removing the cyst (RC group) and 13 "leaving alone" the cyst (LC group). 3D radiographic parameters (primary outcome), 2D parameters and clinical records (secondary outcome) involving both hard and soft tissues were evaluated for four periods (T1: immediate postoperative, T2: 6-month, T3: 12-month, and T4: 2- to 5- year follow-up). Possible confounding factors, including sinus anatomical features and implant distribution, were also analyzed to eliminate their disturbance. RESULTS: The 3D volumetric change rate of bone grafts in the RC group (-9.32% ± 10.01%) from T2 to T3 was significantly lower than that in the LC group (-19.8% ± 10.59%) (p < .05). The change rate of apical bone height (ABH), endo-sinus bone gain (ESBG) and other 2D parameters were not significantly different between the two groups. 5.3% implants in RC group and 9.1% implants in LC group failed during follow-ups. 0% postoperative complications were observed in RC group. The Schneiderian membrane of RC group was significantly thinner than that of LC group at two measuring points in sinus. CONCLUSION: The present study demonstrated that compared to AP retainment, AP removal before MSFA and immediate implant placement can obtain higher bone graft volumetric stability and favorable prognosis.

Genetically modified immunomodulatory cell-based biomaterials in tissue regeneration and engineering.

To date, the wide application of cell-based biomaterials in tissue engineering and regeneration is remarkably hampered by immune rejection. Reducing the immunogenicity of cell-based biomaterials has become the latest direction in biomaterial research. Recently, genetically modified cell-based biomaterials with immunomodulatory genes have become a feasible solution to the immunogenicity problem. In this review, recent advances and future challenges of genetically modified immunomodulatory cell-based biomaterials are elaborated, including fabrication approaches, mechanisms of common immunomodulatory genes, application and, more importantly, current preclinical and clinical advances. The fabrication approaches can be categorized into commonly used (e.g., virus transfection) and newly developed approaches. The immunomodulatory mechanisms of representative genes involve complicated cell signaling pathways and metabolic activities. Wide application in curing multiple end-term diseases and replacing lifelong immunosuppressive therapy in multiple cell and organ transplantation models is demonstrated. Most significantly, practices of genetically modified organ transplantation have been conducted on brain-dead human decedent and even on living patients after a series of experiments on nonhuman primates. Nevertheless, uncertain biosecurity, nonspecific effects and overlooked personalization of current genetically modified immunomodulatory cell-based biomaterials are shortcomings that remain to be overcome.

Prognosis Comparison Between Nipple-Sparing Mastectomy and Total Mastectomy in Breast Cancer: A Case-Control Study After Propensity Score Matching.

BACKGROUND: Currently, the operation rate of nipple-sparing mastectomy (NSM) is increasing. However, the long-term prognosis of NSM is not well documented. We utilized the Surveillance, Epidemiology, and End Results (SEER) database to analyze the long-term prognosis of NSM compared with total mastectomy (TM). METHODS: Population-level data of female breast cancer patients treated with NSM and TM were extracted from 1998 to 2016 from the SEER database. Propensity score matching (PSM) was performed to reduce the influence of selection bias and confounding variables in comparisons. Kaplan-Meier analysis, log-rank test, and Cox proportional hazard regression were performed. RESULTS: A total of 5765 patients underwent NSM, which increased from 266 in 2004-2009 to 5370 in 2010-2016. A total of 134,528 patients underwent TM, and the number of patients undergoing TM continued to decline. The overall survival (OS) and breast cancer-specific survival (BCSS) were similar between the NSM group and the TM group (P = 0.058 and 0.87, respectively). For OS, subgroup analysis showed that patients with age ≥ 46, White race, median household income ≥ $70,000, hormone receptor-positive, and HER2 negative had a better prognosis for treatment with NSM. There was no significant difference in BCSS between the NSM group and the TM group. CONCLUSIONS: In recent years, the clinical application of NSM has been increasing. NSM is a proper procedure for breast cancer patients to achieve long-term survival.

Therapeutic effect of Keap1-Nrf2-ARE pathway-related drugs on age-related eye diseases through anti-oxidative stress.

Age-related eye diseases, including cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), are the leading causes of vision loss in the world. Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye. The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body. This pathway is also active in the development of age-related eye diseases. A variety of drugs have been shown to treat age-related eye diseases through the Keap1-Nrf2-ARE (Kelch-like ECH-Associating protein 1- nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway. This review describes the role of oxidative stress in the development of age-related eye diseases, the function and regulation of the Keap1-Nrf2-ARE pathway, and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.