Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma.

Despite significant advances in therapy, the 5-year survival rates for patients with advanced stage oral cancers still remains poor as an appropriate treatment has not been found yet, due to side effects of chemo/radiotherapy. Verbascoside (VB), a major bioactive constituent of the Tsoong herb, displays pharmacological properties by exhibiting anti-oxidative, anti-inflammatory and anti-cancer activities. However, the underlining function and mechanism of VB in human oral squamous cell carcinoma (OSCC) remains unclear. In this study, we show that VB significantly decreased the viability and metastasis of HN4 and HN6 tumor cells, while promoting apoptosis. A xenograft OSCC mouse model further showed that intraperitoneal injection of VB strongly inhibited growth and lung metastasis of implanted tumor cells. Immunoblot analysis confirmed that VB effectively suppressed nuclear factor (NF)-κB activation and downstream Bcl-2/Bcl-XL expression, resulting in increased OSCC cell apoptosis. In addition, VB suppressed mRNA and protein expression of matrix metalloproteinase-9 via suppression of NF-κB activation, thereby inhibiting tumor cell metastasis. Inspiringly, compared to cisplatin-treated group, VB is a biocompatible agent without signficant side effects in vivo. Collectively, our results demonstrate that VB effectively inhibits OSCC tumor cell growth and metastasis via suppression of IκB kinase complex (IKK)/NF-κB-related signaling activation, suggesting that VB has potential use as a potent anticancer agent in OSCC therapeutic strategies.

Immediate implant placement and complete mouth rehabilitation with CAD-CAM titanium frameworks and cemented crowns for a patient with severe periodontal disease: A clinical report.

The technique of immediate implantation has been widely used to reduce treatment time and bone loss after extraction. However, immediate implant placement in infected extraction sockets is generally contraindicated. This clinical report describes a treatment protocol for immediate implantation after the extraction of teeth with generalized chronic periodontitis. The technique used for the oral rehabilitation used computer-assisted design and computer-assisted manufacturing (CAD-CAM) titanium frameworks and cemented zirconia crowns. The titanium frameworks overcame suboptimal implant position and the cemented crowns provided excellent function and esthetics despite the locations of screw-access openings. No clinical complications occurred during a 13-month follow-up.

Clinicopathological Characteristics and Outcome Predictors in Squamous Cell Carcinoma of the Maxillary Gingiva and Hard Palate.

PURPOSE: Squamous cell carcinoma (SCC) located in the maxillary gingiva and hard palate is relatively rare. There are few published guidelines for the treatment of SCC of the maxilla. The aim of the present study was to characterize the clinicopathologic features of SCC of the maxillary gingiva and hard palate and determine factors that predict outcome and lead to a strategic treatment plan. MATERIALS AND METHODS: A retrospective cohort study of patients with SCC of the maxillary gingiva and hard palate was conducted from 2003 to 2012 at the Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University. Clinicopathologic characteristics, treatments, outcome predictors, and 3- and 5-year overall survival rates were analyzed. The Kaplan-Meier method was used to evaluate 3- and 5-year overall survival rates. Univariate and multivariate Cox regression analyses were used to identify predictors of survival. A P value less than .05 was considered statistically significant. RESULTS: The 3- and 5-year survival rates of the 62 participants were 66.6 and 57.3%, respectively. Univariate analyses showed statistically significant (P < .05) associations between patient survival rate and tumor differentiation grade, T classification, marginal status, cervical lymphatics, and local recurrence. Occult lymph node metastases of maxillary SCC in tumor stages T2 to T4 occurred in 20 to 40% of patients. Patients who presented with lesions located after the first premolar plane area and received postoperative radiotherapy had a better prognosis. CONCLUSION: Elective neck dissection is recommended for management of T2 to T4 SCCs in the maxillary gingiva and hard palate. Postoperative radiotherapy can improve the prognosis and decrease the recurrence of SCC after the first premolar plane area.

Extended Free Forearm Flap for Treatment of Temporomandibular Joint Pseudoankylosis.

Pseudoankylosis of temporomandibular joint (TMJ) is characterized by limited mouth opening and impaired mandibular mobility induced by pathologic factors outside the joint itself, usually leading to compromised speech, swallowing, and breath functions. Multiple surgical approaches or reconstructive procedures have been proposed to resolve the joint pseudoankylosis and restore the mandibular movement for these affected patients. Free forearm flap has been widely used in reconstruction for various congenital or acquired defects or deformities; however, this flap has been rarely employed for TMJ pseudoankylosis in the literature. Here, the authors reported that noma-induced TMJ pseudoankylosis was diagnosed and successfully treated by extended free forearm flap with length over 10 cm in a Chinese female patient.

Reconstruction of palatomaxillary defects following cancer ablation with temporalis muscle flap in medically compromised patients: a 15-year single institutional experience.

OBJECTIVES: Successful reconstruction of palatomaxillary defects following cancer ablation represents a formidable challenge for surgeons to achieve consistently favorable outcomes. The purpose of this article is to present our experience in oncologic palatomaxillary repair with temporalis muscle flap (TMF) for medically compromised patients who are not ideal candidates for microvascular reconstruction at a Chinese tertiary referral hospital over a 15-year period (1998-2012). METHOD: A retrospective chart review was performed to identify patients with compromised medical conditions who underwent oncologic palatomaxillary reconstruction using TMF. Patients' demographics, clinicopathological variables, and surgical techniques were presented. Postoperative functional and aesthetic outcomes were assessed by measurements and patients self-evaluations. RESULTS: Sixty-nine TMFs were successfully harvested and used for immediate oncologic palatomaxillary reconstruction in 67 patients (31 males and 36 females, mean age 60.4 years) with diverse primary malignancies. These patients' co-morbidities included systemic diseases, preoperative chemotherapy/radiotherapy, and elder over 65 years which precluded the ideal utility of free flaps. Fifty-one patients remained alive without disease, while nine had recurrences/metastases and seven died during the follow-up (0.5-10.4 years, mean 3.7 years). All flaps survived with only partial necroses in four cases. Complications and donor-site morbidities were minimal with five transient facial paralysis and four mild diplopia and enophthalmos. Unrestricted diet and mouth opening, intelligible speech, and satisfactory temporal aesthetics were obtained in most patients. CONCLUSION: The TMF is a reliable, versatile, and alternative option for oncologic palatomaxillary reconstruction with satisfactory functional and aesthetic outcomes and minimal complications, especially when appropriately selected for those medically compromised patients.

Spontaneous malignant transformation in craniomaxillofacial fibrous dysplasia.

Spontaneous malignant transformation in craniomaxillofacial fibrous dysplasia (FD) is extremely rare and its clinicopathological characteristics remain largely unknown. Here, we aimed to characterize the epidemiology and clinicopathological features of malignancies arising from preexisting FD by presenting data from a Chinese tertiary referral hospital and review of English and Chinese literatures. The craniomaxillofacial disease registry of Shanghai Ninth People's Hospital was searched and reviewed to collect relevant information for patients diagnosed as malignant transformation in craniomaxillofacial FD between January 1993 and December 2010. An English and Chinese literature review was conducted to retrieve pertinent cases published in the past 2 decades with preset inclusion criteria. All included cases were further analyzed with regard to associated clinical and pathological variables. Three cases with osteosarcoma arising from previous craniomaxillofacial FD were found at our institution and 35 other cases were identified by literature review. These uncommon entities usually occurred in adults with a mean age of 39.8 years and equal gender preponderance. Maxilla remained the most common sites for malignancies followed by mandible and zygoma. Most malignancies were diagnosed as osteosarcoma followed by fibrosarcoma, chondrosarcoma, and malignant fibrous histiocytoma. Radical resection alone or with postoperative radiotherapy/chemotherapy remains the main treatment strategy with unfavorable prognosis due to local recurrence and distant metastasis. Taken together, our findings might for the first time provide the comprehensive information regarding the epidemiology, clinicopathological features, treatment, and prognosis of malignancies in craniomaxillofacial FD. Further investigations are warranted to improve early diagnosis and proper treatment for these uncommon entities.

Development and validation of a nomogram to predict occult cervical metastasis in early oral squamous cell carcinoma.

Background: Lack of adequate objectivity and universality, available models are still difficult to be applied to clinical practice in predicting occult cervical metastasis of early oral squamous cell carcinoma (OSCC). Taking abnormal metabolic state into consideration, the current model is helpful to distinguish those patients with or without occult cervical metastasis. Methods: This study retrospectively analyzed 330 OSCC patients initially diagnosed cT1-2N0M0 stage and received neck dissection from January 2020 to July 2022. The occult cervical metastasis was identified by pathological examination.. After screening independent risk factors using logistic regression, patients were divided into training and validation cohorts at the ratio of 2:1 randomly, and a novel diagnostic model was constructed. Performances of this model were evaluated by the area under the curve (AUC), calibrating curve, decision curve analysis (DCA) and clinical impact curve (CIC). Results: Of the 330 included patients {age mean [standard deviation (SD)], 61.24 (12.99) years; 202 (61.2%) males}, 49 (14.8%) had occult nodal metastasis. Five variables, including body mass index (BMI) [high odds ratio (OR): 1.132; 95% confidence interval (CI): 1.019-1.258, P=0.021], primary tumor site (tongue & floor of mouth (TF) OR: 3.756; 95% CI: 1.295-10.898, P=0.015), depth of invasion (DOI) (5-10 mm OR: 2.973; 95% CI: 1.266-6.981; P=0.012), pathological differentiation (Poor differentiation OR: 2.65; 95% CI: 1.341-5.239; P=0.005), and diabetes (OR: 3.123; 95% CI: 1.23-7.929; P=0.017) were screened to establish the predictive model. In training cohort (n=220), this model achieved an AUC of 0.814 and had a sensitivity of 78.1% and specificity of 70.2%. Calibration plots showed favorable consistency between the prediction of the model and actual observations (Hosmer-Lemeshow value >0.05). Decision curve analysis (DCA) and clinical impact curve (CIC) showed the model was clinically useful and had better discriminative ability under the threshold probability of 0.5. Above evaluations were verified in the validation cohort (n=110). Compared to previous reported models, the concordance index (C-index), net reclassification index (NRI), and integrated discrimination improvement (IDI) values were superior in both training and validation cohorts (P<0.05). Conclusions: This constructed model might have reference value for clinicians in making neck management decisions of early OSCC patients.

Contribution of SATB2 to the stronger osteogenic potential of bone marrow stromal cells from craniofacial bones.

Previous studies have shown that craniofacial bone marrow stromal cells (BMSCs) have a strong osteogenic potential. However, the mechanism by which BMSCs of various embryonic origins develop diverse osteogenic potentials remains unclear. To investigate the mechanisms regulating osteoblast differentiation in two different types of BMSCs, we compared the temporal and spatial mRNA and protein expression patterns of Satb2 and its downstream gene Hoxa2 by using real-time polymerase chain reaction, Western blotting and fluorescent immunostaining in mandible BMSCs (M-BMSCs) and tibia BMSCs (T-BMSCs) undergoing osteoblast differentiation. Higher levels of alkaline phosphatase, greater calcium accumulation and earlier expression of Runx2 were observed in osteogenic-induced M-BMSCs compared with T-BMSCs. Low levels of Satb2 were detected in both types of uninduced BMSCs but the majority of SATB2 was located in the nuclei of M-BMSCs. Notably, Satb2 was expressed earlier in M-BMSCs and Hoxa2, a downstream target of Satb2, was not expressed in uninduced M-BMSCs or during osteoblast differentiation, just as during embryonic mandible development. In contrast, Hoxa2 was reactivated in T-BMSCs during osteoblast differentiation. Based on these results, we conclude that SATB2 plays a different role during osteoblast differentiation of M-BMSCs and T-BMSCs. The earlier activation of Satb2 expression in M-BMSCs compared with T-BMSCs might explain the stronger osteogenic potential of M-BMSCs.

Differential regulation of proteoglycan-4 expression by IL-1α and TGF-ß1 in rat condylar chondrocytes.

Proteoglycan 4 (PRG4) is a multifaceted glycoprotein that mediates boundary lubrication of articular cartilage and its dysregulation is associated with impaired lubrication and cartilage destruction in multiple synovial joints. However, the spatiotemporal expression of PRG4 and the associated regulatory networks remain largely unknown in the mandibular condylar cartilage that is responsible for homeostasis and functions of the temporomandibular joint. We here investigated the possible regulatory effects of the interleukin-1α (IL-1α) or/and transforming growth factor-ß1 (TGF-ß1) on the expression of PRG4 in primary chondrocytes that were isolated from the superficial layer of the condylar cartilage of the 20-day-old male Sprague-Dawley rats. Both IL-1α and TGF-ß1 have been implicated in joint destruction and repair. Treatment of primary chondrocytes for 24 h with recombinant human (rh) IL-1α (10 ng/ml) resulted in pronounced reduction in the expression levels of PRG4 mRNA and protein, whereas stimulation with rhTGF-ß1 (10 ng/ml) significantly increased the expression levels, as measured by RT-PCR and ELISA, respectively. Moreover, rhTGF-ß1 was capable to antagonize the inhibitory effects on the PRG4 expression caused by rhIL-1α and robustly restored its abundance in the cultured condylar chondrocytes. Taken together, our data indicate that PRG4 is synthesized and secreted by condylar cartilage chondrocytes and its expression is differentially regulated by IL-1α and TGF-ß1. The rhIL-1α-mediated PRG4 repression is reversible and potently antagonized by rhTGF-ß1 in condylar chondrocytes. The observed up-regulation of PRG4 upon rhTGF-ß1 treatment further supports the therapeutic application of rhTGF-ß1 in the treatment of temporomandibular joint osteoarthritis.

Radial forearm free flap for reconstruction of a large defect after radical ablation of carcinoma of the tongue and floor of the mouth: some new modifications.

BACKGROUND: A modified radial forearm free flap was designed to rehabilitate function and to reduce the complications at both donor and recipient sites. METHODS: Between 2003 and 2007, 15 patients with infiltrating squamous cell carcinoma (T(3)-T(4)) of the tongue and/or floor of the mouth underwent hemiglossectomy and resection of the floor of the mouth with microvascular reconstruction using a modified radial forearm flap. The mean size of the forearm flap was 7.5 x 14 cm, and the de-epithelialized area was 7 x 6 cm, requiring no skin graft from the abdomen. Speech intelligibility tests were administered to test postoperative speech and the functional oral intake scale was applied to assess the postoperative swallowing function, and patients reconstructed with pectoralis major myocutaneous flap were used for comparison. RESULTS: All the flaps were successfully transferred. No obvious complications were found in either the oral-maxillofacial or forearm region. The speech intelligibility was better in the modified flap group (p < 0.01). An acceptable swallowing function was also achieved, although the difference was not significant (p > 0.05). CONCLUSIONS: The modified flap used for reconstructing large defects of the tongue and floor of the mouth might be a valid substitute for pectoralis major myocutaneous flap to improve the outcome in individuals with significant oral carcinoma.

Implants placed simultaneously with maxillary sinus floor augmentation in the presence of antral pseudocysts: Presentation of a case series.

OBJECTIVE: To report the outcome of simultaneous placement of dental implants with maxillary sinus elevation in the presence of antral pseudocysts. METHOD AND MATERIALS: This case series involved 14 patients with 28 implants placed simultaneously with maxillary sinus elevation. The psuedocysts were treated by cystic fluid extraction. Postoperative examinations were performed at 3, 6, and 12 months. RESULTS: All restorations were finished 6 to 9 months after implant placement. Nine antral pseudocysts disappeared and five decreased in size. All implants were deemed successful at 1 year postoperatively, showing osseointegration and masticatory function. No mobility was found during the follow-up period. CONCLUSION: In the absence of maxillary sinus infection, the combination of cystic fluid extraction, maxillary sinus elevation, and immediate implantation showed an acceptable clinical outcome in this series of patients.

Application of lateral arm free flap in oral and maxillofacial reconstruction following tumor surgery.

OBJECTIVE: To describe the application of lateral arm free flap (LAFF) in reconstruction of defects in the oral and maxillofacial regions following ablative oncological surgery. SUBJECTS AND METHODS: The study included 16 patients (13 male, 3 female, mean age 56, range 35-69 years). Sixteen LAFF were harvested to reconstruct defects caused by the dissection of malignant tumors of the oral and maxillofacial regions. The tumor was squamous cell carcinoma of the tongue (6 cases), floor of the mouth (4), retromolar area (3), inner cheek (2), and lower gingival (1). Flap sizes ranging from 5 x 7 to 6 x 9 cm were harvested using a sterile tourniquet for bloodless technique. The anastomoses were carried out using a magnifier or microscope. All donor defects were closed primarily. RESULTS: Fourteen flaps healed without venous insufficiency. One flap, in a female patient, survived with mild local microcirculatory obstruction but that of another female patient developed necrosis. There was no significant complication at the donor sites. The advantages of this flap include anatomically reliable vascular supply, accessible donor site, and the aesthetic quality of donor tissue is good. Compared with the radial artery, the posterior radial collateral artery is a nonessential vessel of the arm. The disadvantages are the relatively smaller vessel size for anastomosis and thicker subcutaneous tissue. CONCLUSIONS: For the repair of moderate-sized defects of the maxillofacial area, especially in male patients, the LAFF can be recommended.

Differential expression of inducible nitric oxide synthase in keratocystic odontogenic tumors prior and subsequent to decompression.

The aim of the present study was to investigate the expression of inducible nitric oxide synthase (iNOS) in keratocystic odontogenic tumors (KCOTs) prior and subsequent to decompression and to explore the association between iNOS expression and changes in clinical features. Sixteen pairs of specimens obtained at the time of decompression and subsequent curettages were collected and immunohistochemically examined using an antibody against iNOS. The intensity of iNOS staining was evaluated semi-quantitatively for statistical analysis. Prior to decompression, 87.5% of KCOT samples showed no immunohistochemical reactivity for iNOS. Only 12.5% of samples exhibited slight staining for iNOS in the cytoplasm of cells in the epithelial layer. Subsequent to decompression, all the samples exhibited moderate to intense staining for iNOS in the cytoplasm and membrane of cells in the epithelial and fibrous layers. This increased expression of iNOS following decompression was statistically significant (P<0.01). The results demonstrated distinct expression of iNOS in KCOT samples prior and subsequent to decompression, indicating that iNOS may have a role in mediating changes in clinical features.

Topographic relationship between root apex of mesially and horizontally impacted mandibular third molar and lingual plate: cross-sectional analysis using CBCT.

The present study was aimed to determine the topographic relationship between root apex of the mesially and horizontally impacted mandibular third molar and lingual plate of mandible. The original cone beam computed tomography (CBCT) data of 364 teeth from 223 patients were retrospectively collected and analyzed. The topographic relationship between root apex and lingual plate on cross-sectional CBCT images was classified as non-contact (99), contact (145) and perforation (120). The cross-sectional morphology of lingual plate at the level of root apex was defined as parallel (28), undercut (38), slanted (29) and round (4). The distribution of topographic relationship between root apex and lingual plate significantly associated with gender, impaction depth, root number and lingual plate morphology. Moreover, the average bone thickness of lingual cortex and distance between root apex and the outer surface of lingual plate were 1.02 and 1.39 mm, respectively. Furthermore, multivariate regression analyses identified impaction depth and lingual plate morphology as the risk factors for the contact and perforation subtypes between root apex and lingual plate. Collectively, our findings reveal the topographic proximity of root apex of impacted mandibular third molar to the lingual plate, which might be associated with intraoperative and postoperative complications during tooth extraction.

An excellent navigation system and experience in craniomaxillofacial navigation surgery: a double-center study.

Numerous problems regarding craniomaxillofacial navigation surgery are not well understood. In this study, we performed a double-center clinical study to quantitatively evaluate the characteristics of our navigation system and experience in craniomaxillofacial navigation surgery. Fifty-six patients with craniomaxillofacial disease were included and randomly divided into experimental (using our AccuNavi-A system) and control (using Strker system) groups to compare the surgical effects. The results revealed that the average pre-operative planning time was 32.32 mins vs 29.74 mins between the experimental and control group, respectively (p > 0.05). The average operative time was 295.61 mins vs 233.56 mins (p > 0.05). The point registration orientation accuracy was 0.83 mm vs 0.92 mm. The maximal average preoperative navigation orientation accuracy was 1.03 mm vs 1.17 mm. The maximal average persistent navigation orientation accuracy was 1.15 mm vs 0.09 mm. The maximal average navigation orientation accuracy after registration recovery was 1.15 mm vs 1.39 mm between the experimental and control group. All patients healed, and their function and profile improved. These findings demonstrate that although surgeons should consider the patients' time and monetary costs, our qualified navigation surgery system and experience could offer an accurate guide during a variety of craniomaxillofacial surgeries.

[Expression of full-length spleen tyrosine kinase in the oral squamous cell carcinoma and its relationship with tumor invasion and metastasis].

OBJECTIVE: To investigate the expression of full-length spleen tyrosine kinase [SYK (L)] mRNA and protein in human oral squamous cell carcinoma (OSCC) as well as its possible effects on the invasion and metastasis of OSCC. METHODS: The expression of SYK (L) was detected in 27 cases of OSCC tissues and its matched adjacent non-cancerous tissues by real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry. Fourteen cases of normal oral gingival tissues were also analyzed as a normal control. RESULTS: Reduced mRNA and protein expression of SYK (L) in OSCC tissues was observed compared with that in normal oral gingival tissues (P<0.01) and adjacent non-cancerous tissues (P<0.05). SYK(L) expression was significantly associated with lymph-node metastasis (P<0.05). CONCLUSION: SYK(L) is a candidate tumor suppressor for OSCC tissues, and has an inhibitive effect on the initiation, proliferation, and lymph-node metastasis of human OSCC.

[The influence of drilling pulling ways and cooling systems on dental implant surgery].

PURPOSE: To study the effect of different ways of pulling the drilling burs and cooling systems on alveolar bone temperature of the surgical area, and explore the changes of temperature field in dental implants. METHODS: Forty-eight unified standard artificial (nylon) bone blocks were fabricated and divided into 6 groups according to different drilling pulling ways and cooling systems. The changes of bone temperature field were detected in 6 groups, and the highest temperature in temperature field was measured and recorded. The date was analyzed with SPSS 12.0 software package for ANOVA. RESULTS: The temperature in the surgical area using internal cooling systems under the same drilling pulling was lower than using external cooling systems. The temperature in the surgical area using secondary drilling pulling way was lower than using direct drilling methods under the same cooling systems. The temperature in the surgical area using secondary drilling pulling way was the lowest when internal cooling systems was adopted(P<0.05). CONCLUSIONS: Drilling pulling way and internal cooling systems can effectively reduce the temperature in the surgical area, lessen heat production and improve the success rate of dental implants.

Perioperative glucocorticosteroid treatment delays early healing of a mandible wound by inhibiting osteogenic differentiation.

AIM: The purpose of this study is to investigate the effects of dexamethasone on repair of a critical size defect of the mandible in male Sprague-Dawley rats. MATERIALS AND METHODS: Fifty rats were divided into 2 groups: saline control and dexamethasone-treated groups. A 1 mm × 3 mm full-thickness bone defect was created at the inferior border of the mandible. Saline or dexamethasone was administered once a day for 5 days after postoperative palinesthesia. On days 1, 3, 6, 10 and 17, after cessation of drug administration, 5 samples from each group were analysed. The bone defect healing process was examined and analysed by stereology, radiology, histology and histochemical staining for total collagen, tartrate-resistant acid phosphatase staining for osteoclasts and immunohistochemical staining for the COX-2, RUNX2 and osteocalcin antigens. RESULTS: The dexamethasone-treated rats exhibited significantly lower radiopacity properties compared to the control rats. Histological staining revealed that the osteogenic differentiation and maturation of a callus in the defect region was significantly delayed from day 1 to day 10 in the dexamethasone group after cessation of drug administration compared to the control group. Consistent with the histological data, the level of total collagen protein was significantly lower in the dexamethasone group than in the control group. However, there was no significant difference between the 2 groups at day 17. Immunohistochemical analysis of COX-2, RUNX2 and osteocalcin expression showed that, at day 1, COX-2 and RUNX2 expression in the dexamethasone group was significantly lower than in the control group. There was no significant difference in osteocalcin expression between the two groups at each time point. There was no significant difference in the number of osteoclasts between the two groups. CONCLUSION: In a model of bone healing of a mandible defect, dexamethasone-treated rats exhibited impaired osteogenic differentiation and maturation due to the inhibition of COX-2, osteogenic gene, RUNX2 and collagen protein expression, which resulted in delayed bone repair. Although perioperative short-term therapy did not exhibit long-term effects on wound healing of the maxillofacial bone, the application of glucocorticoids should be cautiously considered in the clinic.

Critical-size calvarial bone defects healing in a mouse model with silk scaffolds and SATB2-modified iPSCs.

Induced pluripotent stem cells (iPSCs) can differentiate into mineralizing cells and thus have a great potential in application in engineered bone substitutes with bioactive scaffolds in regeneration medicine. In the current study we characterized and demonstrated the pluripotency and osteogenic differentiation of mouse iPSCs. To enhance the osteogenic differentiation of iPSCs, we then transduced the iPSCs with the potent transcription factor, nuclear matrix protein SATB2. We observed that in SATB2-overexpressing iPSCs there were increased mineral nodule formation and elevated mRNA levels of key osteogenic genes, osterix (OSX), Runx2, bone sialoprotein (BSP) and osteocalcin (OCN). Moreover, the mRNA levels of HoxA2 was reduced after SATB2 overexpression in iPSCs. The SATB2-overexpressing iPSCs were then combined with silk scaffolds and transplanted into critical-size calvarial bone defects created in nude mice. Five weeks post-surgery, radiological and micro-CT analysis revealed enhanced new bone formation in calvarial defects in SATB2 group. Histological analysis also showed increased new bone formation and mineralization in the SATB2 group. In conclusion, the results demonstrate that SATB2 facilitates the differentiation of iPSCs towards osteoblast-lineage cells by repressing HoxA2 and augmenting the functions of the osteoblast determinants Runx2, BSP and OCN.

[One-staged correction of alveolar cleft and lip and nasal deformities secondary to lip cleft].

OBJECTIVE: To investigate individualized one-staged correction of alveolar cleft and lip and nasal deformities secondary to lip cleft. METHODS: The alveolar cleft and lip and nasal deformities secondary to lip cleft were corrected in one stage. RESULTS: From 2004 to 2007, 37 cases were treated. 33 patients were treated successfully with primary healing in bony recipient area. Cancellous bone exposure happened in 3 cases. The wounds healed after debridement and drainage. The cosmetic results were satisfactory. CONCLUSIONS: One-staged correction of alveolar cleft and the lip and nasal deformities secondary to lip cleft can achieve good results.