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Skeletal muscle mass and function deteriorate with ageing. Adiponectin receptors (APNrs), mainly activated by adiponectin, participate in various physiological activities and have varying signalling pathways at different ages. This study aimed to explore whether discrepant performance exists in APNr activation regulating young and aged muscle satellite cells (MUSCs) and whether age-related muscle dysfunction could be alleviated upon APNr activation.The gastrocnemius muscle phenotype was observed in male mice aged 2 and 18 months. An APNr agonist (AdipoRon) was used in vitro and in vivo to investigate the changes in cell biological behaviours and whether muscle dysfunction could be retarded after APNr activation.Aged mice exhibited decreased muscle mass and increased fat infiltration. APNr activation inhibited C2C12 cells and young MUSCs (YMUSCs) proliferation but showed no obvious effect on aged MUSCs (AMUSCs). Moreover, APNr activation inhibited the migration of both YMUSCs and AMUSCs. Interestingly, APNr activation hampered the myogenic differentiation but advanced the adipogenic differentiation of YMUSCs, yet exact opposite results were presented in AMUSCs. It was demonstrated that Wnt and PI3K signalling pathways may mediate the phenotypic differences. Furthermore, in vivo experiments verified that APNr activation ameliorated age-related muscle atrophy and excessive fat infiltration.APNr activation exerted dual effects on the regulation of myogenesis and adipogenesis of YMUSCs and AMUSCs and rescued age-related skeletal muscle dysfunction.

Hippo pathway is a cellular regulatory pathway composed of core molecules such as MST1/2, LATS1/2, SAV1, MOB1A/B and downstream YAP/TAZ. Fully involved in regulating cell proliferation, differentiation, migration and apoptosis, the Hippo pathway is critical in regulating stem cells of oral origin, for instance, DPSCs and PDLSCs, enamel formation and periodontium regeneration. Here, we summarized the Hippo pathway involved in these progresses and concluded crosstalks of the Hippo pathway with BCL-2, ERK1/2, ROCK, TGF-β/BMP and Wnt/β-catenin pathways, hoping to provide foundation for further clinical therapy.

Background Temple filler injection is one of the most common minimally invasive cosmetic procedures involving the face; however, vascular complications are not uncommon. Objectives This study aimed to investigate the anatomy of the temporal vessels and provide a more accurate protocol for temple filler injection. Methods Computed tomography (CT) scans of 56 cadaveric heads injected with lead oxide were obtained. We then used Mimics software to construct 3-dimensional (3D) images of the temporal vessels described by a coordinate system based on the bilateral tragus and right lateral canthus. Results In the XOY plane, the superficial temporal artery (STA), middle temporal artery (MTA), zygomatico-orbital artery (ZOA), posterior branch of the deep temporal artery (PDTA), and lateral margin of the orbital rim divide the temple into 4 parts (A, B, C, and D). The probabilities of the STA, MTA, ZOA, and PDTA appearing in parts A, B, C, and D were 30.73%, 37.06%, 39.48%, and 77.18%, respectively. In 3D images, these vessels together compose an arterial network that is anastomosed with other vessels, such as the external carotid, facial, and ocular arteries. Conclusions 3D CT images can digitally elucidate the exact positions of temporal vessels in a coordinate system, improving the safety of temple filler injections in a clinical setting.

Objectives This study aims to establish a machine learn-based decision support system for the treatment of dental and maxillofacial malformations and verify its feasibility. Materials and Methods Between January 2015 to August 2020, 574 patients with spiral CT and have confirmed diagnosis of dento-maxillofacial deformities were used to train the diagnostic model based on five kind of machine learning algorithm. The diagnostic performance of the algorithm was compared with the ground truth and evaluated by accuracy, sensitivity, specifcity, and area under the ROC curve (AUC). The adaptive artificial bee colony (aABC) algorithm was used to calculate the orthognathic surgical plan based on cephalometrics in the normal population. The algorithm was used to automatically generate surgical plans for 50 patients and the plans were rated by three experienced maxillofacial surgeons. Results The binary relevance extreme gradient boosting model delivered the best overall performance. The final diagnosis success rates on six different kinds of maxillofacial deformities were all over 90%, except for maxillary overdevelopment (89.27%). Conclusions The machine learning algorithms show high accuracy and effectiveness in diagnosis and surgical plan design of dento-maxillofacial deformities. The AUC of all diagnostic types was greater than 0.88. The median score for surgical plan was 9. The scheme scores were further improved after human-computer interaction. Clinical Relevance The decision support system based on machine learning could be used for automatic diagnosis and surgical design for patients with dento-maxillofacial deformities, which will help improving diagnostic efciency and provide expertise to areas with lower medical levels.

Treatment of skeletal Class II patients with dual bite and idiopathic condylar resorption (ICR) is challenging for orthodontists because of the unstable position of the mandible as well as skeletal relapse attributed to improper seating of the mandibular condyles. This case report describes the successful treatment of an 18-year-old Mongolian man diagnosed with centric relation–maximum intercuspation discrepancy and ICR. After making a definitive diagnosis from verified centric relation using bilateral manipulation, orthodontic treatment was initiated followed by three-dimensional computer-aided design/computer-aided manufacturing prebent titanium plate–guided sagittal split ramus osteotomy and genioplasty. Postoperative 3D superimposition demonstrated that this surgical guide approach provided accurate repositioning of the condyles, which were well positioned in the fossae. Complete orthodontic and surgical treatment time was 24 months. The patient's facial appearance and occlusion improved significantly, and a stable result was obtained with a 1-year follow-up.

Background Strengthening weakened ligament tissues with injectable fillers to improve their supportive effect may achieve the aesthetic goal of face lifting. Objectives The aim of the study was to design an injectable technique for enhancing the true facial ligaments and dissect the ligaments to provide anatomical guidance for effective injection. Methods Six true facial ligaments were chosen as target anatomical sites for injection. Specimens were dissected, and 3-dimensional (3D) images were reconstructed to confirm the exact location of each injection site and to confirm that the proposed injection routes will not cause dangerous vascular damage. A total of 5 patients received the injections; 3D images were taken before and after the injections for comparison and clinical outcome assessments. Results The injection technique was designed to target 6 true facial ligaments, as follows. Site 1 targeted the temporal ligamentous adhesion region to lift the lateral ends of the eyebrows. Site 2 targeted the region of the lateral orbital thickening to lift the lateral canthus. Site 3 and site 4 targeted the zygomatic retaining ligaments and zygomatic cutaneous ligaments, respectively, to augment the soft tissues of the midface. Site 5 targeted the region of the maxillary ligament to lessen the nasolabial folds, and site 6 targeted the mandibular ligament to reduce the marionette line. Conclusions This site-specific injection technique targeting the true ligaments may lead to increased efficiency and accuracy of face rejuvenation and exert a lifting effect. Level of Evidence: 4

Robotic surgical system has been gradually applied in thyroid neoplasms as a novel treatment for years, with presenting some superiorities as well as limitations. To compare the effectiveness and safety of robotic surgery with open surgery for the patients with thyroid neoplasms, this review was conducted METHODS: We performed electronic search in CENTRAL, MEDLINE, EMBASE, CNKI, CBM, Opengray, and Sciencepaper Online databases and manual search in specific online databases and according to the reference list of relevant papers to get all the studies that compared the effectiveness and safety of robotic surgery with that of open surgery for patients with thyroid neoplasms. Last update was conducted in March 2020. Randomized-controlled trials, case-control studies, cohort studies, and cross-sectional surveys were all included.In this review, 59 studies were included: two RCTs, 15 NRSs, 40 cohort studies, and two cross-sectional studies. Robotic surgery was found to be associated with longer operative duration, less retrieved lymph nodes, higher postoperative thyroglobulin before radioactive iodine ablation, similar complication incidence but less blood loss, better functional recovery, and higher cosmetic satisfaction compared to open surgery.Robotic surgery is a safe and feasible approach with remarkable superiority in reducing intraoperative damage and improving patients' quality of life compared to open surgery for thyroid neoplasms. Meanwhile, this procedure is also associated with long operative duration, insufficient removal of neck lymph nodes, which need to be given careful consideration.

Background/purpose: Mechanical stretch plays a key role in promoting proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs) in distraction osteogenesis (DO). A better understanding of how the extracellular biomechanical stimulation is transferred to intracellular signal expression will benefit DO. Focal adhesion kinase (FAK) is a key factor in integrin signaling pathway. However, little is known about the effect of integrin-FAK signaling during the process of stretch induced osteogenic differentiation of BMSCs. Materials and methods: A specific short hairpin RNAs (shRNAs) lentiviral expression vector was used to silence Fak gene and a well-established in vitro uniaxial dynamic stretching device was applied to stimulate DO. Fak silencing was confirmed by fluorescence microscopy and the detection of Fak mRNA and FAK, p-FAK protein expression. Alkaline phosphatase (ALP) activity, expression of osteogenic differentiation markers - runt-related transcription factor 2 (RUNX2/Runx2) and alkaline phosphatase (Alp) together with integrin upstream signal transduction molecules integrin beta-1 (ITGB1/Itgb1) and downstream signal transduction molecules integrin-linked kinase (ILK) were detected after the stretch. Results: The results showed that mechanical stretch in control groups significantly induced the osteogenic differentiation of BMSCs with increased ALP activity, expression of RUNX2/Runx2 and Alp, together with upregulated ITGB1/Itgb1 and ILK, which all vanished in Fak silencing group. Conclusion: Silencing of the Fak gene inhibited the osteogenic differentiation of rat BMSCs induced by in vitro mechanical stretch through integrin signaling pathway. Keywords: Distraction osteogenesis, Focal adhesion kinase, Integrin signaling pathway, Mesenchymal stem cells, Mechanical stretch

Rare diseases are usually genetic, chronic and incurable disorders with a relatively low incidence. Developments in the diagnosis and management of rare diseases have been relatively slow due to a lack of sufficient profit motivation and market to attract research by companies. However, due to the attention of government and society as well as economic development, rare diseases have been gradually become an increasing concern. As several dental-craniofacial manifestations are associated with rare diseases, we summarize them in this study to help dentists and oral maxillofacial surgeons provide an early diagnosis and subsequent management for patients with these rare diseases., Oral Diseases: Dental and craniofacial indications associated with rare diseases Rare diseases are typically genetic, chronic, incurable disorders with a relatively low incidence, and a number of dental and craniofacial manifestations are associated with such diseases. A team headed by En Luo and Hanghang Liu at Sichuan University in China conducted a large-scale review of the manifestations and treatment of rare diseases related to dental and craniofacial disorders. The authors found that in their early stages, several rare diseases exhibit distinctive dental and craniofacial characteristics. Provided they understand the clinical features, dentists and oral surgeons are the individuals best placed to make an early identification of such diseases. The authors believe that their findings will help clinicians fully grasp the related clinical signs and potential treatments of rare diseases, thereby facilitating early diagnosis and patient management as well as improving prognosis.

The biology of immediate post-extraction implant osseointegration is mediated by a coordinated cascade of osteoblast-osteoclast interactions. The aim of this study was to develop a dual-delivery system that allowed sequential release of substance P (SP) to promote bone regeneration and alendronate (ALN) to reduce bone resorption, which will improve the implant osseointegration. We used coaxial electrospinning to fabricate the core-shell poly lactic-co-glycolic acid (PLGA)/gelatin nanofibers, which consists of SP in the shell and ALN in the core. This programmed delivery system was shown to release SP and ALN sequentially to match the spatio-temporal specificity of bone healing. The migration assay demonstrated that the SP-ALN dual-delivery system increased bone marrow mesenchymal stem cells (BMSCs) transmigration. Besides, the expression of osteogenic/osteoclastic markers, Alizarin Red staining, tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and bone resorption experiment showed that the dual-delivery system can render a microenvironment favorable for osteogenic differentiation and adverse to osteoclastogenesis. Using a rat immediate implant model, we validated the promoted osteogenic property and osseointegration around the implants of SP-ALN dual-delivery system by micro-computed tomography (micro-CT) and histological analysis. These findings suggest that the dual-delivery system with time-controlled release of SP and ALN by core-shell nanofibers provides a promising strategy to facilitate immediate implant osseointegration through favorable osteogenesis. STATEMENT OF SIGNIFICANCE: Immediate implant placement is potentially challenged by the difficulties in achieving primary implant stability and early osteogenesis. Initial period of osteointegration is regulated by osteoblastic/osteoclastic cells resulting in a coordinated healing process. To have an efficient bone regeneration, the coaxial electrospinning was used to fabricate a programmed dual-delivery system. The SP released rapidly and favored for BMSCs migration and osteogenic differentiation, while the sustained release of ALN can reduce the bone resorption. The rat immediate implant model indicated that the SP-ALN dual-delivery system could present the promoted peri‑implant osteogenic property and osseointegration through modulating the osteogenesis-osteoclastogenesis balance. This work highlights the sequential dual delivery of SP and ALN has a promising potential of achieving enhanced osseointegration for immediate implant placement.

The cover image is based on the Original Article An adiponectin receptor agonist promote osteogenesis via regulating bone-fat balance by Hanghang Liu et al., https://doi.org/10.1111/cpr.13035. [Image: see text]

Objectives Adiponectin signalling has been considered to be a promising target to treat diabetes‐related osteoporosis. However, contradictory results regarding bone formation were observed due to the various isoforms of adiponectin. Therefore, it would be necessary to investigate the effect of adiponectin receptor signals in regulating bone‐fat balance. Materials and Methods We primarily applied a newly found specific activator for adiponectin receptor, AdipoRon, to treat bone metabolism‐related cells to investigate the role of Adiponectin receptor signals on bone‐fat balance. We then established femur defect mouse model and treated them with AdipoRon to see whether adiponectin receptor activation could promote bone regeneration. Results We found that AdipoRon could slightly inhibit the proliferation of pre‐osteoblast and pre‐osteoclast, but AdipoRon showed no effect on the viability of mesenchymal stromal cells. AdipoRon could remarkably promote cell migration of mesenchymal stromal cells. Additionally, AdipoRon promoted osteogenesis in both pre‐osteoblasts and mesenchymal cells. Besides, AdipoRon significantly inhibited osteoclastogenesis via its direct impact on pre‐osteoclast and its indirect inhibition of RANKL in osteoblast. Moreover, mesenchymal stromal stems cells showed obviously decreased adipogenesis when treated with AdipoRon. Consistently, AdipoRon‐treated mice showed faster bone regeneration and repressed adipogenesis. Conclusions Our study demonstrated a pro‐osteogenic, anti‐adipogenic and anti‐osteoclastogenic effect of adiponectin receptor activation in young mice, which suggested adiponectin receptor signalling was involved in bone regeneration and bone‐fat balance regulation., Adiponectin receptors 1 and 2 are expressed early in mesenchymal stem cells lineage and in precursors including pre‐osteoblast, pre‐osteoclasts and chondrocytes. Using an adiponectin receptor agonist AdipoRon, our study demonstrated a pro‐osteogenic, anti‐adipogenic and anti‐osteoclastogenic effect of adiponectin receptor activation in young mice, which suggested adiponectin receptor signalling was involved in bone regeneration and bone‐fat balance regulation.

Background Nasal filler placement is associated with a high risk of blindness. The arterial supply to the upper nose overlaying the nasal bones is poorly understood. Objectives The aim of this study was to visualize and analyze the deployment of the ophthalmic and facial angiosomes in the upper nose to help prevent blindness following nasal filler injections. Methods The arterial systems of 62 cadaveric heads were filled with lead oxide contrast agent, and computed tomography (CT) images were acquired and reconstructed in 3 dimensions. Results Twenty-six of the cadaveric noses examined demonstrated clear CT images of the facial and ophthalmic angiosomes in the upper nose. The Type 1 upper nose (15.4%) is supplied by 2 independent ophthalmic angiosomes that communicate indirectly through a choke anastomosis. The Type 2 upper nose (38.5%) is supplied by 2 ophthalmic angiosomes with a true anastomosis between them. The Type 3 upper nose (46.1%) is supplied by both ophthalmic and facial angiosomes with true anastomoses across the dorsal midline. These true anastomoses are mediated by the radix arcade in 46% of the noses and involve the dorsal nasal artery in 65% of the cases. The anastomoses all cross the upper dorsal midline and are directly linked to the ophthalmic angiosome. Conclusions The deployment and anastomosis of the facial and ophthalmic angiosomes in the upper nose fall into 3 major patterns. About 85% of the noses have true anastomotic arteries that cross the upper dorsal midline and are directly linked to the ophthalmic circulation. Dorsum filler injection poses a significant risk of blindness.

Lung cancer has become the leading cause of cancer-related death worldwide. Oxidative stress plays important roles in the pathogenesis of lung cancer. Many natural products show antioxidative activities in cancer treatment. Zi Shen decoction (ZSD) is a classic prescription for the treatment of lung disease. However, its effect on lung cancer lacks evidence-based efficacy. In this study, we investigated the anticancer effects of ZSD on lung cancer in vivo and in vitro. Our results showed that oral administration of ZSD suppressed the Lewis lung cancer (LLC) growth in a subcutaneous allograft model and promoted necrosis and inflammatory cell infiltration in the tumor tissues. Furthermore, ZSD not only inhibited tumor cell proliferation and migration but also induced cell apoptosis in lung cancer cells. PI3K/AKT signaling is well characterized in response to oxidative stress. The bioinformatics analysis and western blot assays suggested that ZSD decreased the enzyme activity of PI3K and AKT in vivo and in vitro. We also found that the AKT/GSK-3β/β-catenin pathway medicated anticancer effect of ZSD in lung cancer cells. In conclusion, we demonstrate for the first time that ZSD possesses antitumor properties, highlighting its potential use as an alternative strategy or adjuvant treatment for lung cancer therapy.

Lung cancer has become the leading cause of cancer-related death worldwide. Oxidative stress plays important roles in the pathogenesis of lung cancer. Many natural products show antioxidative activities in cancer treatment. Zi Shen decoction (ZSD) is a classic prescription for the treatment of lung disease. However, its effect on lung cancer lacks evidence-based efficacy. In this study, we investigated the anticancer effects of ZSD on lung cancer in vivo and in vitro. Our results showed that oral administration of ZSD suppressed the Lewis lung cancer (LLC) growth in a subcutaneous allograft model and promoted necrosis and inflammatory cell infiltration in the tumor tissues. Furthermore, ZSD not only inhibited tumor cell proliferation and migration but also induced cell apoptosis in lung cancer cells. PI3K/AKT signaling is well characterized in response to oxidative stress. The bioinformatics analysis and western blot assays suggested that ZSD decreased the enzyme activity of PI3K and AKT in vivo and in vitro. We also found that the AKT/GSK-3β/β-catenin pathway medicated anticancer effect of ZSD in lung cancer cells. In conclusion, we demonstrate for the first time that ZSD possesses antitumor properties, highlighting its potential use as an alternative strategy or adjuvant treatment for lung cancer therapy.

Objectives Bone regeneration is a complex process modulated by multiple growth factors and hormones during long regeneration period; thus, designing biomaterials with the capacity to deliver multiple bioactive molecules and obtain sustained release has gained an increasing popularity in recent years. This study is aimed to evaluate the effect of a novel core‐shell electrospun fibre loaded with dexamethasone (DEX) and bone morphogenetic protein‐2 (BMP‐2) on bone regeneration. Materials and methods The core‐shell electrospun fibres were fabricated by coaxial electrospinning technology, which were composed of poly‐D, L‐lactide (PLA) shell and poly (ethylene glycol) (PEG) core embedded with BMP‐2 and DEX‐loaded micelles. Morphology, hydrophilicity, gradation, release profile of BMP‐2 and DEX, and cytological behaviour on bone marrow mesenchymal stem cells (BMSCs) were characterized. Furthermore, the effect on bone regeneration was evaluated via critical‐sized calvarial defect model. Results The electrospun fibres were featured by the core‐shell fibrous architecture and a suitable degradation rate. The sustained release of DEX and BMP‐2 was up to 562 hours. The osteogenic gene expression and calcium deposition of BMSCs were significantly enhanced, indicating the osteoinduction capacity of electrospun fibres. This core‐shell fibre could accelerate repair of calvarial defects in vivo via synergistic effect. Conclusions This core‐shell electrospun fibre loaded with DEX and BMP‐2 can act synergistically to enhance bone regeneration, which stands as a strong potential candidate for repairing bone defects.

Treating dentofacial deformities secondary to condylar resorption is a remarkable clinical challenge. Combined orthodontic treatment and orthognathic surgery is currently the main treatment scheme and is often integrated with temporomandibular joint surgery or conservative treatment according to the severity of condylar resorption. This paper discussed the etiology, clinical features, imaging features, treatment options, and prophylaxis of condylar resorption.髁突吸收是下颌骨髁突体积不可逆性缩小的一种临床现象，常继发牙颌面畸形。目前，正畸-正颌联合治疗是主要的治疗方案；同时，根据髁突吸收的严重程度，常结合关节手术或以药物、牙合板为主的保守治疗。本文从髁突吸收继发牙颌面畸形的病因、临床特点、影像学特点、治疗选择及其预防作一系统论述。.

Background Filler injection is a popular cosmetic procedure, but it can entail vascular complications. Periorbital injections have the highest risk within the entire injection area. Objectives The authors sought to systematically screen for periorbital arterial variations prior to treatment. Methods The external carotid arteries of 10 cadaveric heads were infused with adequate lead oxide contrast. The facial and superficial temporal arteries of another 11 cadaveric heads were injected with the contrast in sequential order. Computed tomography (CT) scanning was performed after injection of contrast, and 3-dimensional (3D) CT scans were reconstructed using validated algorithms. Results Three types of periorbital blood vessels were found to derive from the ophthalmic artery, including 30% directly originating from the ophthalmic artery, 65% originating from its trochlear branch, and 5% originating from its supraorbital branch. In the forehead, the ophthalmic artery, originating from the internal carotid arteries, formed anastomoses between the frontal branch of the superficial temporal artery, originating from the external carotid artery, with the deep and superficial branches of the supratrochlear and supraorbital arteries, respectively. The lateral orbit and malar plexus can be classified into 4 types based on the trunk artery: the zygomatic orbital artery (27%), the transverse facial artery (23%), the premasseteric branch of the facial artery (19%), and all 3 contributing equally (31%). Conclusions Postmortem 3D CT can map periorbital arterial variations. The branching pattern of the ophthalmic artery, the ophthalmic angiosome in the forehead, and the distribution of the lateral orbit and malar plexus were identified at high resolution to guide clinical practice.

The efficacy of stem cell-based bone tissue engineering has been hampered by cell death and limited fate control. A smart cell culture system with the capability of sequentially delivering multiple factors in specific growth stages, like the mechanism of the natural extracellular matrix modulating tissue formation, is attractive for enhancing cell activity and controlling cell fate. Here, a bone forming peptide-1 (BFP-1)-laden mesoporous silica nanoparticles (pep@MSNs) incorporated adhesion peptide, containing the arginine-glycine-aspartic acid (RGD) domain, modified alginate hydrogel (RA) system (pep@MSNs-RA) was developed to promote the activity and stimulate osteo-differentiation of human mesenchymal stem cells (hMSCs) in sequence. The survivability and proliferation of hMSCs were enhanced in the adhesion peptide modified hydrogel. Next, BFP-1 released from pep@MSNs induced hMSCs osteo-differentiation after the proliferation stage. Moreover, BFP-1 near the cells was self-captured by the additional cell-peptide cross-linked networks formed by the ligands (RGD) binding to receptors on the cell surface, leading to long-term sustained osteo-stimulation of hMSCs. The results suggest that independent and sequential stimulation in proliferation and osteo-differentiation stages could synergistically enhance the survivability, expansion, and osteogenesis of hMSCs, as compared to stimulating alone or simultaneously. Overall, this study provided a new and valid strategy for stem cell expansion and osteo-differentiation in 2D or 3D culture systems, possessing potential applications in 3D bio-printing and tissue regeneration.

Titanium implants are widely used in dental clinics and orthopaedic surgery. However, bone formation surrounding the implant is relatively slow after inserting the implant. The current study assessed the effects of bone marrow stromal cells (BMSCs) with forced expression of special AT-rich sequence-binding protein 2 (SATB2) on the osseointegration of titanium implants. To determine whether SATB2 overexpression in BMSCs can enhance the osseointegration of implants, BMSCs were infected with the retrovirus encoding Satb2 (pBABE-Satb2) and were locally applied to bone defects before implanting the titanium implants in the mouse femur. Seven and twenty-one days after implantation, the femora were isolated for immunohistochemical (IHC) staining, haematoxylin eosin (H&E) staining, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and micro-computed tomography (μCT) analysis. IHC staining analysis revealed that SATB2-overexpressing BMSCs were intensely distributed in the bone tissue surrounding the implant. Histological analysis showed that SATB2-overexpressing BMSCs significantly enhanced new bone formation and bone-to-implant contact 3 weeks after implantation. Real-time qRT-PCR results showed that the local delivery of SATB2-overexpressing BMSCs enhanced expression levels of potent osteogenic transcription factors and bone matrix proteins in the implantation sites. μCT analysis demonstrated that SATB2-overexpressing BMSCs significantly increased the density of the newly formed bone surrounding the implant 3 weeks post-operatively. These results conclude that local delivery of SATB2-overexpressing BMSCs significantly accelerates osseointegration of titanium implants. These results provide support for future pharmacological and clinical applications of SATB2, which accelerates bone regeneration around titanium implants.

Recent studies have suggested that genomic diversity may play a key role in different clinical outcomes, and the importance of SNPs is becoming increasingly clear. In this article, we summarize the bioactivity of SNPs that may affect the sensitivity to or possibility of drug reactions that occur among the signaling pathways of regularly used immunosuppressants, such as glucocorticoids, azathioprine, tacrolimus, mycophenolate mofetil, cyclophosphamide and methotrexate. The development of bioinformatics, including machine learning models, has enabled prediction of the proper immunosuppressant dosage with minimal adverse drug reactions for patients after organ transplantation or for those with autoimmune diseases. This article provides a theoretical basis for the personalized use of immunosuppressants in the future.

Throughout the twenty-first century, robotic surgery has been used in multiple oral surgical procedures for the treatment of head and neck tumors and non-malignant diseases. With the assistance of robotic surgical systems, maxillofacial surgery is performed with less blood loss, fewer complications, shorter hospitalization and better cosmetic results than standard open surgery. However, the application of robotic surgery techniques to the treatment of head and neck diseases remains in an experimental stage, and the long-lasting effects on surgical morbidity, oncologic control and quality of life are yet to be established. More well-designed studies are needed before this approach can be recommended as a standard treatment paradigm. Nonetheless, robotic surgical systems will inevitably be extended to maxillofacial surgery. This article reviews the current clinical applications of robotic surgery in the head and neck region and highlights the benefits and limitations of current robotic surgical systems.

Mesenchymal stem cells (MSCs) are able to self-renew and differentiate into tissues of mesenchymal origin, making them to be significant for cell-based therapies, such as metabolic bone diseases and bone repair. Regulating the differentiation of MSCs is significant for bone regeneration. Electrospun fibers mimicking natural extracellular matrix (ECM), is an effective artificial ECM to regulate the behaviors and fates of MSCs. The aligned electrospun fibers can modulate polar cell pattern of bone mesenchymal stem cells, which leads to more obvious osteogenic differentiation. Apart from the topographic effect of electrospun fibers, mechanical cues can also intervene the cell behaviors. In this study, the osteogenic differentiation of rat bone mesenchymal stem cells was evaluated, which were cultured on aligned/random electrospun fiber mats materials under mechanical tension intervention. Scanning electron microscope and immune-fluorescent staining were used to directly observe the polarity changing of cellular morphology and cytoskeleton. The results proved that aligned electrospun fibers could be more conducive to promote osteogenic differentiation of rat bone mesenchymal stem cells and this promotion of osteogenic differentiation was enhanced by tension intervention. These results were correlated to the quantitative real-time PCR assay. In general, culturing rat bone mesenchymal stem cells on electrospun fibers under the intervention of mechanical tension is an effective way to mimic a more real cellular microenvironment.

Rare diseases are genetic, chronic, and incurable disorders with relatively low prevalence. Thus, diagnosis and management strategies for such diseases are currently limited. This situation is exacerbated by insufficient medical sources for these diseases. The National Health and Health Committee of China recently first provided a clear definition of 121 rare diseases in the Chinese population. In this study, we summarize several dental-craniofacial manifestations associated with some rare diseases to provide a reference for dentists and oral maxillofacial surgeons aiming at fast-tracking diagnosis for the management of these rare diseases.罕见病是一类遗传性的、慢性的、不可治愈且发病率相对较低的疾病。由于其发病率低，相关医疗资源较为缺乏，对其诊断及治疗的研究也受到限制。近期国家五部委发布的《第一批罕见病目录》纳入了121种罕见病，第一次明确界定了我国罕见病的范围。临床资料显示一些罕见病常伴有牙颌面表现，为了实现对罕见病的早期诊断与治疗，本文对目录纳入的罕见病牙颌面临床表现及相关治疗手段进行总结，以期为口腔科医生提供临床诊断依据。.

An alendronate (AL)-embedded zinc phosphate (ZnP) coating was synthesized on biodegradable Zn to control its corrosion and long-term degradation while maintaining its bio-functionality. The AL molecules were well incorporated into the ZnP and the hybrid coating was homogeneously compact and dense. The coating not only reduced the corrosion current density and the Zn2+ release rate, but also ensured a uniform long-term degradation behavior of Zn in PBS. The coating retained a desirable balanced osteo-functionality of pro-osteoblast and anti-osteoclast response. The above achieved performance can be credited to the nature of the organic-inorganic components of this coating and its high quality.

Background/purpose Dental informatics (DI) is a new emerging interdiscipline for medical informatics (MI) and general dentistry, and dental information technology (d-IT) is a parallel research field. The purpose of this study was to investigate the current situation of DI and d-IT in China, evaluate the achievements, analyze the weakness, and anticipate the future development. Materials and methods Publications about DI and d-IT in English and Chinese journals by international and Chinese researchers were searched through literature reviews. The funds supporting DI and d-IT in China were manually searched. DI and d-IT education in China was analyzed by website search and telephone interview. Results The investigation indicated that China started research in DI and d-IT fields from the late 1970s, but the development has become more rapid in the last 10 years. Both Chinese and international publications have increased sharply within the last decade. The Chinese government kept a stable increasing investment in DI and d-IT scientific projects and Chinese researchers made influential achievements in certain fields of DI and d-IT, such as computer-aided design and computer-aided manufacturing (CAD-CAM) development and application, computer-assisted manufacture of facial prosthesis, and three-dimensional (3D)-assisted dental education. Conclusion DI and d-IT have developed rapidly in China in recent years. However, there are some problems which remain to be resolved.

This study investigated the efficacy of human osteoprotegerin (hOPG) transgene to accelerate osteointegration of titanium implant in ovariectomized (OVX) rats. Bone marrow stromal cells transduced with Ad-hOPG-EGFP could sustainedly express hOPG. Osteoclast precursor RAW264.7 cells treated by the hOPG were examined by tartrate-resistant acid phosphatase (TRAP) staining and bone slice resorption assay. The results showed differentiation and function of osteoclasts were significantly suppressed by hOPG in vitro. Ad-hOPG-EGFP was locally administered to the bone defect prior to implant placement in OVX and sham rats. After 3, 7, 28 days of implantation, the femurs were harvested for molecular and histological analyses. Successful transgene expression was confirmed by western blot and cryosectioning. A significant reduction in TRAP+ numbers was detected in Ad-hOPG-EGFP group. Real-time reverse transcriptase-PCR examination revealed that hOPG transgene markedly diminished the expression of cathepsin K and receptor activator for nuclear factor-κ B ligand in vivo. The transgene hOPG modification revealed a marked increasing osteointegration and restored implant stability in OVX rats (P

Purpose The objective of this study was to investigate cancellous bone response to strontium-doped hydroxyapatite (SrHA) in ovariectomized (OVX) rats. Methods Hydroxyapatite (HA) and 10%SrHA (HA with 10 mol% calcium substituted by strontium) implants were prepared and characterized by scanning electronic microscopy (SEM), energy dispersive microanalysis (EDX) and X-ray diffraction (XRD). Twelve weeks after bilateral ovariectomy, 20 rats randomly received HA or 10%SrHA implants in the right distal femur, with 10 animals in each group. Eight weeks after implantation, specimens were harvested and analyzed by micro-computed tomography (micro-CT) and histology. Results Compared with HA, 10%SrHA raised the percentage bone volume by 42.6%, bone-to-implant contact by 47.1%, mean trabecular number by 27.3%, mean trabecular thickness by 31.5% and mean connectivity density by 37.4%, while it decreased mean trabecular separation by 20.1% in micro-CT evaluation. 10%SrHA also increased the bone area density by 47.6% in histological analysis. Conclusions With the HA implants as controls, the 10%SrHA implants were shown to increase bone density and bone-to-implant contact, and improve trabecular architecture in the vicinity of implant surfaces.

Objectives To investigate the mechanism of mechanical stimulation in bone formation and regeneration during distraction osteogenesis. Materials and methods In this study, microarray technology was used to investigate the time course of bone-related molecular changes in distraction osteogenesis in rats. Real-time PCR and Western-blot analyses were used to confirm the expression of genes identified in microarrays. Meanwhile, we used a lentivirus vector to inhibit Fak expression, in order to identify the osteogenic effect of Fak and Fak-Mapk pathway during distraction osteogenesis. Results Several components of the Wnt and Hippo pathways were found to be up- or down-regulated during distraction osteogenesis by microarray. Meanwhile, it was found that Fak, Src, Raf-1, Erk1, Jnk and p38-Mapk were up-regulated during gradual distraction, compared with consolidation. To further determine whether Fak-Mapk pathway played an important role in distraction osteogenesis, Fak was disrupted with a lentivirus vector. The expressions levels of p-Fak, p-Erk1/2, p-JNK and p-p38Mapk were decreased. Meanwhile, a poor early and late osteogenesis effect was found in the shRNA-Fak group. Conclusion It was inferred that the mechanical stimulus induces increased expression of Fak and activates Fak-Mapk pathway, by activation of Erk, Jnk and p38-Mapk pathway, and that Fak at least, in part, plays an important role in maintaining osteogenic effect by activating Fak-Mapk pathway during distraction osteogenesis.

Recent studies have demonstrated the stimulatory effects of adiponectin on bone formation, but the mechanism underlying these effects remains unclear. The Wnt/β-catenin pathway, one of the most important pathways in osteogenesis, has rarely been associated with the osteogenic effects of adiponectin in previous studies. The present study was designed to investigate the effects of adiponectin on bone mesenchymal stem cell (BMSC) osteogenic differentiation and bone formation through the Wnt/β-catenin pathway. We detected adiponectin receptor expression in BMSCs, constructed a recombinant adenovirus containing the human adiponectin gene, and then used the adenovirus to transfect BMSCs in vitro or injected the adenovirus into bone defect areas in animal models. Wnt/β-catenin pathway and osteogenesis were detected by real-time PCR, western blotting, immunofluorescence, HE staining and micro-CT. In both our in vivo and in vitro experiments, we detected higher gene and protein expression levels of the Wnt/β-catenin pathway-related factors β-catenin and cyclinD1 in adiponectin transgenic BMSCs and rats. Similar results were noted regarding the gene and protein expression levels of osteogenesis-related genes. In addition, more new bone formation was observed in the adiponectin-treated groups. Our results indicate that adiponectin could facilitate BMSC osteogenic differentiation and osteogenesis, and the Wnt/β-catenin pathway was involved in the osteogenic effect of adiponectin.

Hypoparathyroidism (HP) is a disorder characterized by low levels of PTH which lead to hypocalcemia, hyperphosphatemia, and low bone turnover. The most common cause of the disease is accidental removal of the parathyroid glands during thyroid surgery. Novel therapies for HP are needed, but testing them requires reliable animal models of acquired HP. Here, we demonstrate the generation of two mouse models of acquired HP. In the GFP-PTX model, mice with green fluorescent protein (GFP) expressed specifically in the parathyroids (PTHcre-mTmG) were created by crossing PTHcre+ mice with Rosa-mTmGfl/fl mice. Green fluorescing parathyroid glands are easily identified under a fluorescence dissecting microscope and parathyroidectomy is performed in less than 20 min. After fluorescence-guided surgery, mice are profoundly hypocalcemic. Contrary to the traditional thyro-parathyroidectomy, this precise surgical approach leaves thyroid glands and thyroid function intact. The second model, which does not require surgery, is based on a diphtheria-toxin approach. PTHcre-iDTR mice, which express the diphtheria toxin (DT) receptor specifically in the parathyroids, were generated by crossing the inducible DTR mouse with the PTHcre mouse. Parathyroid cells are thus rendered sensitive to diphtheria toxin (DT) and can be selectively destroyed by systemically injecting mice with DT. The resulting hypocalcemic phenotype is stable.

Objective To evaluate the changes in the jaws and the upper airways of unilateral temporomandibular joint ankylosis patients who underwent condylar reconstruction via autogenous coronoid process grafts using cone-beam computed tomography (CBCT). Study design The 27 included patients underwent CBCT examinations at three stages: T0 (within two weeks before surgery), T1 (two weeks after surgery), and T2 (an average of 13 months after surgery). Forty items related to the maxillofacial hard tissues and the upper airway collected at the three times and the coronoid process graft volumes after surgery were compared. Results Some integral items related to the mandibular hard tissues exhibited statistical difference shortly after surgery. Some integral items related to maxillofacial hard tissues changing obviously long period after surgery may result from graft remodeling. Asymmetry-related item regarding local neo-condyle and some airway items were significantly different between T0 and T1. Due to variations in graft remodeling, some related local asymmetry items and airway items differed significantly between T0 and T2. Conclusions Anteriorly and inferiorly located neo-condyles and a trend toward the pronation of the mandible were observed and the narrowness of the upper airway was improved shortly after surgery. The grafts remodeled differently and some integral and asymmetry items related to neo-condyle changed. The improvements in the upper airway were slightly reduced.