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Objective: This study presents an innovative articular fossa prosthesis generated by the envelope surface of condyle movement, and compares its mandible movements, muscle activities, and joint reaction forces with two temporomandibular joint (TMJ) prostheses using multibody musculoskeletal simulation. Methods: A healthy 23-year-old female was recruited for this study. Cone-beam computed tomographic (CBCT) was performed to reconstruct the mandibular bone geometry. A customized TMJ fossa prosthesis was designed based on the subject-specific envelope surface of condyle movement (ESCM). Mandibular kinematics and jaw-closing muscle electromyography (EMG) were simultaneously recorded during maximum jaw opening-closing movements. To validate our prosthesis design, a mandibular musculoskeletal model was established using flexible multibody dynamics and the obtained kinematics and EMG data. The Biomet fossa prosthesis and the ellipsoidal fossa prosthesis designed by imitating the lower limb prostheses were used for comparison. Simulations were performed to analyze the effects of different fossa prostheses on jaw opening-closing motions, mandibular muscle activation, and contact forces. Results: The maximum opening displacement for the envelope-based fossa prosthesis was greater than those for Biomet and ellipsoidal prostheses (36 mm, 35 mm, and 33 mm, respectively). The mandibular musculoskeletal model with ellipsoidal prosthesis led to dislocation near maximal jaw opening. Compared to Biomet, the envelope-based fossa reduced the digastric and lateral pterygoid activation at maximal jaw opening. It also reduced the maximal resistance to condylar sliding on the intact side by 63.2 N. Conclusion: A customized TMJ fossa prosthesis was successfully developed using the ESCM concept. Our study of musculoskeletal multibody modeling has highlighted its advantages and potential. The artificial fossa design successfully achieved a wider condylar range of motion. It also reduced the activation of jaw opening muscles on the affected side and resistance on the intact side. This study showed that an ESCM-based approach may be useful for optimizing TMJ fossa prostheses design., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wang, Chen, Guo, Xu and Guo.)

Objective: To define the clinical factors that influence local recurrence and survival in patients with lower gingival squamous cell carcinoma (LGSCC) and determine whether bone invasion is an independent prognostic factor for them., Methods: A total of 104 patients with LGSCC hospitalized in Peking University Stomatology Hospital from June 2013 to December 2015 were enrolled in this retrospective study.All the patients were followed-up for more than 3 years.The degree of bone invasion was assessed using preoperative imaging data (CT and panoramic radiograph).The degree of bone invasion was divi-ded into four categories: no bone invasion, invasion of cortical bone, invasion of bone marrow cavity, and invasion of the mandibular canal.According to the central position of tumor, it was divided into two types: anterior mandibular invasion (anterior region of the mental foramen) and posterior mandibular invasion (posterior region of the mental foramen)., Results: of different invasion depth groups were compared using Mann-Whitney U test. P value < 0.05 was considered to be statistically significant.Kaplan-Meier survival analysis method was used to draw survival curve, and COX regression was used to explore the risk ratio ( HR ) and 95% confidence interval ( CI ) of prognostic factors of LGSCC., Results: The follow-up results showed that the 1-, 3-, and 5-year survival rates of LGSCC in this group were 91%, 84%, 82%, respectively.32.7%(34/104) of patients had cervical lymph node metastasis.The cervical lymph node metastasis rate of the anterior segment of the mandible was 12.5%(2/16), and 36.4%(32/88) for the posterior segment of the mandible ( P < 0.05).Univariate and multivariate COX analysis showed that the N stage and local recurrence were the prognostic factors of LGSCC patients ( P < 0.05)., Conclusion: As the degree of mandibular invasion increases, the prognosis of patients with mandibular gum cancer becomes worse.N stage and local recurrence are prognostic risk factors for LGSCC.The incidence of cervical lymph node metastasis for LGSCC is related to the primary tumor location.It is concluded that tumors located at the posterior of the mandible might be more prone to cervical lymph node metastasis than the anterior of the mandible.Thus various levels of cervical lymph node dissection strategies should be adopted for different sites of LGSCC.

Background: Long-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients., Methods: The clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed after administering anti-resorptive and/or anti-angiogenic drugs; the imaging and histological change of the extraction socket were observed. Moreover, the cell function of gingival fibroblasts was analyzed after the treatment with anti-resorptive and/or anti-angiogenic drugs in order to evaluate their effect on the gingival tissue healing of the extraction socket., Results: Patients treated with anti-angiogenic and anti-resorptive drugs had an advanced clinical stage and a bigger proportion of necrotic jawbone exposure compared to patients treated with anti-resorptive drugs alone. In vivo study further indicated a greater loss of mucosa tissue coverage above the tooth extraction in mice treated with sunitinib (Suti) + zoledronate (Zole) group (7/10) vs. Zole group (3/10) and Suti group (1/10). Micro-computed tomography (CT) and histological data showed that the new bone formation in the extraction socket was lower in Suti + Zole and Zole groups vs. Suti and control groups. In vitro data showed that the anti-angiogenic drugs had a stronger inhibitory ability on the proliferation and migration function of gingival fibroblasts than anti-resorptive drugs, and the inhibitory effect was obviously enhanced after combining zoledronate and sunitinib., Conclusion: Our findings provided support for a synergistic contribution of anti-angiogenic drugs to anti-resorptive drugs-based MRONJ. Importantly, the present study revealed that anti-angiogenic drugs alone do not induce severe MRONJ but aggravate the degree of MRONJ via the enhanced inhibitory function of gingival fibroblasts based on anti-resorptive drugs., (© 2023. The Author(s).)

Objective: To summarize the pathological characteristics of medication-related osteonecrosis of the jaw (MRONJ) specimens after jaw curettage or jaw osteotomy treatment and to comprehensively analyze the relationship between the different pathological features, treatment methods, and treatment effects to provide new ideas for effective treatment of MRONJ in clinical work., Methods: The clinical and pathological data were collected from 23 patients with MRONJ who were treated with curettage (18 patients) and jaw osteotomy (5 patients) at the Department of Oral and Maxillofacial Surgery of Peking University Hospital of Stomatology between June 2014 and December 2015. The pathological characteristics of MRONJ were summarized and analyzed with treatment effects based on various surgical treatment methods. The diagnostic criteria and disease staging of MRONJ were determined according to the 2014 American Association of Oral and Maxillofacial Surgeon's Position Paper., Results: In this study, 5 patients have treated with jaw segmental osteotomy, and all of them were in stage Ⅲ; the other 18 patients were treated with jaw curettage, including 5 patients in stage Ⅱ and 13 patients in stage Ⅲ. The pathological features of MRONJ in five cases of jaw segmental osteotomy were divided into three adjacent regions from shallow to deep: inflammation region (IR), sclerosis region (SR), and bone remodeling layer (BRL). Moreover, three types of pathological features of specimens from traditional curettage were defined as type 1 (IR), type 2 (IR + SR), and type 3 (IR + SR + BRL). The pathological features of the patients treated with jaw curettage were: type Ⅰ, 38.9% (7/18); type Ⅱ, 44.4% (8/18); type Ⅲ, 16.7% (3/18). Complete healing was achieved in 5 patients treated with jaw segmental osteo-tomy. Moreover, 2 cases with type Ⅰ, 1 case with type Ⅱ, and 1 with type Ⅲ completely healed after jaw curettage, while 5 cases with type Ⅰ, 7 cases with type Ⅱ, and 2 cases with type Ⅲ experienced recurrence after surgery., Conclusion: Pathological features of continuous regions of inflammation, sclerosis, and bone remodeling layer were identified from shallow to deep, based on the microscopic observation of jaw segmental osteotomy samples. Insufficient removal of the sclerotic region during jaw curettage that blocks the required blood, nutritional factors, and mesenchymal stem cells seems to be a common cause for failed treatment of MRONJ after curettage surgery.

Objective: To discover the factors that may affect the use of selective tracheostomy among patients who have undergone head and neck surgeries with free flap reconstruction, so that the patients will not need tracheostomy nor receive the unnecessary treatment., Methods: Five hundred and thirty-three patients who had undergone head and neck surgery with free flap reconstruction operated by the same team of surgery at Department of Oral and Maxillofacial Surgery at Peking University School of Stomatology from 2015 to 2016 were reviewed. Three hundred and twenty-one (60.2%) of these patients underwent selective tracheostomy. All the patients' demographic information, operation-related information, prior treatments, comorbidities and complications were recorded and analyzed., Results: The patients with defects of the tongue, mouth floor, oropharynx and bilateral mandible, who underwent neck dissection and with previous radiotherapy and smoking habit were more likely to get selective tracheostomy. Usage of bulky soft tissue flap might also add to the risk of airway obstruction and the need of selective tracheostomy, while other factors were not significantly related to the risk of postoperative airway obstruction and the patients could be kept safe without selective tracheostomy. Most cases without tracheostomy were kept safe except one case, while 8.39% of the patients with tracheostomy suffered from tracheostomy related complications, mainly pneumonia and hemorrhage of the tracheostomy wound, yet none led to serious consequences or even death., Conclusion: Selective tracheostomy is not necessary for patients who have undergone head and neck surgeries with free flap reconstruction except that there are defects at the tongue, oropharynx and mandible. Neck dissection, bulky soft tissue flap reconstruction, previous radiotherapy and smoking habit may also add to the risk of postoperative airway obstruction, while a favorable decision would involve a combination of all the above factors to assure the safety of the postoperative airway for the patients undergone head and neck surgeries with free flap reconstruction.

We explored the feasibility and efficacy of a degradable magnesium (Mg) alloy guided bone regeneration (GBR) in the treatment of bone defects after tooth extraction. A GBR membrane (MAR-Gide (MG)) was used to treat a mandibular second molar (M2M)-distal bone defect (DBD). In eight beagle dogs, bilateral mandibular second and fourth premolars were hemi-sected. The distal roots were removed to create a two-wall bony defect of dimension 5 mm × 5 mm × 5 mm to simulate M2M-DBD. Thirty-two bone defects were assigned randomly into four groups according to GBR membranes (MG and Bio-Gide (BG)) applied and the time of killing (3 months and 6 months after surgery). The osteogenesis of bone defects and MG degradation were analyzed using micro-CT, histology (staining, tartrate-resistant acid phosphatase), and inductively coupled plasma mass spectrometry. MG did not increase the prevalence of infection, wound dehiscence, or subcutaneous emphysema compared with those using BG. Trabecular volume/total volume at 3 months (63.71 ± 10.4% vs . 59.97 ± 8.94%) was significantly higher in the group MG than that in the group BG. Implanted MG was degraded completely within 3 months, and "island-shaped" new bone was found near MG degradation products. A significant difference was not found in vertical bone height or percent of new bone formation (45.44 ± 12.28% vs . 43.49 ± 7.12%) between the groups. The concentration of rare-earth elements in mandibular lymph nodes of the group MG was significantly higher than that of the group BG ( P ≤ 0.017) but did not lead to histopathological changes. In summary, MG exhibited good biocompatibility and clinical applicability compared with BG in vivo. The osteogenic effect of MG could be enhanced by regulating the degradation rate of Mg-alloy., Competing Interests: The authors declare that there are no conflicts of interest regarding publication of this manuscript., (Copyright © 2022 Zi-Yu Yan et al.)

Reconstruction of Brown's Class III maxillary defect can be challenging due to the complex geometry of maxilla. We aimed to introduce an improved method for maxillary reconstruction with a composite deep circumflex iliac artery (DCIA) flap aided by virtual surgical planning and intraoperative navigation. A 27-year-old woman diagnosed with left maxillary fibromyxoma was admitted to our institution in December 2018. Pre-operative facial and iliac computed tomography data were obtained for virtual surgical planning. Personalized cutting template, tooth-supported surgical guide, and rapid prototype model with reconstructed orbital floor were printed for pre-operative preparation. Surgery was completely guided by the intraoperative navigation system. The root mean square estimate of the reconstructed area was 3.68 mm. The average errors measured on the lateral and medial DCIA segments were 0.61 and 0.85 mm, respectively. Application of virtual surgical planning and intraoperative navigation could potentially enhance the reconstruction outcomes.

Objective: To establish an animal model with malignant tumor in the skull base-infratemporal region, and to explore the role of iodine staining technique in identifying tumor tissues with Micro-CT data., Methods: Sedation anesthesia was carried out on 12 BABL/c nude mice using inhaled isoflurane, and then WSU-HN6 cells that cultured and immortalized from human tongue squamous cell carcinoma were injected into the right infratemporal fossa via the submandibular area. The procedure was carried out under ultrasonographic guidance. The nude mice were sacrificed after 3 weeks observation. The head specimens were fixed and scanned by Micro-CT, and repeated scans were performed after staining with 3.75% compound iodine solution. Following decalcification in 20% EDTA for 2-4 weeks, the head specimens were embedded and sectioned. Hematoxylin and eosin staining and Pan-Keratin immunohistochemical staining were carried out. Bright-field microscopy and stereomicroscopy were used to visualize. The Micro-CT data were analyzed using iPlan software (Brainlab)., Results: Non-traumatic ultrasonography was used to guide HN-6 cells injection and confirm skull-base tumor formation in all the animals. Ultrasonographic guidance reduced the risk of cervical vessel injury when transferring tumor cells into the skull base space. An obvious asymmetrical appearance was detected via ultrasonography 3 weeks after tumor cell injection. The Micro-CT analysis showed that the bone was obviously damaged on the right side of the skull base, but the soft tissue image was unrecognizable. After four days staining with compound iodine solution, the morphology of the tumor and surrounding soft tissue could be clearly identified. Hematoxylin and eosin staining showed the tumor formation of the right infratemporal fossa region accompanied by bone destruction. Human keratin immunohistochemical staining showed that the tumor tissue originated from human squamous cell carcinoma, and the polynuclear osteoclasts could be seen at the margin of the skull base bone resorption., Conclusion: The animal model with malignant tumor in the skull base-infratemporal region could be successfully established via submandibular injection under ultrasound-guidance. Bone changes of the skull were easily observed on Micro-CT, but the tumor counter was not able to be distinguished from surrounding soft tissue. The 3.75% compound iodine staining of the head specimen could help discern the tumor and surrounding soft tissue in more details.

Objective: To detect the expression of cartilage oligomeric matrix protein (COMP) in the synovial chondromatosis of the temporomandibular joint (TMJSC), and to discuss the possible interactions between COMP, transforming growth factor (TGF)-β3, TGF-β1 and bone morphogenetic protein-2 (BMP-2) in the development of this neoplastic disease., Methods: Patients in Peking University School and Hospital of Stomatology from January 2011 to February 2020 were selected, who had complete medical records, TMJSC was verified histologically after operation. The expressions of COMP, TGF-β3, TGF-β1 and BMP-2 in the TMJSC of the temporomandibular joint were detected by immunohistochemistry and quantitative real-time PCR (RT-PCR) at the protein level and mRNA level respectively, compared with the normal synovial tissue of temporomandibular joint. The histological morphology, protein expression and distribution of TMJSC tissues were observed microscopically, and the positive staining proteins were counted and scored. SPSS 22.0 statistical software was used to analyze the expression differences between the related proteins in TMJSC tissue and the normal synovial tissue of temporomandibular joint and to compare their differences. P < 0.05 indicated that the difference was statistically significant., Results: Immunohistochemical results showed that the positive expression of COMP in TMJSC tissues was mostly found in synovial tissues and chondrocytes adjacent to synovial tissues, and the difference was statistically significant, compared with the normal temporomandibular joint synovial tissues. The positive expression of COMP was significantly different between recurrent TMJSC and non-recurrent ones. The positive expressions of TGF-β3, TGF-β1 and BMP-2 were higher than the normal synovial tissue, and were also mostly found in the synovial cells and adjacent chondrocytes, which was further confirmed by Western blot. According to the RT-PCR results, the expressions of COMP , TGF-β3 , TGF-β1 and BMP-2 in TMJSC were higher than those in the normal synovial tissue., Conclusion: The expression of COMP in TMJSC of temporomandibular joint increased significantly, compared with the normal synovial tissue. There may be interactions between COMP and cytokines related to the proliferation and differentiation, like TGF-β3, TGF-β1 and BMP-2, which may play a potential role in the pathogenesis of TMJSC.

Background: The periodontal healing distal to the mandibular second molar (M2M) after coronectomy of the M3M has shown controversial results. We aimed to combine a digital method with cone-beam computed tomography (CBCT) and estimate periodontal healing of M2M after M3M coronectomy. An accurate and stable indicator in three dimensions was also explored tentatively., Methods: Patients with a M3M in contact with the inferior alveolar canal were included. CBCT was applied immediately after coronectomy (baseline) and 6-months later. Data were investigated with digital software for registration. Previously reported and coronectomy-related factors were included for univariate and multivariate analyses., Results: A total of 181 patients (213 M3Ms) completed 6-month follow-up. Significant reduction in the distal intra-bony defect (DBD) depth of the M2M was shown (1.28 ± 1.24 mm, P < 0.001). DBD depth of the M2M at baseline was the most influential factor (r = 0.59), followed by preoperative M3M condition, age, rotation and migration of the root complex. Remaining enamel (OR = 6.93) and small retromolar space (0.67) contributed to re-contact of the root complex and M2M. Bone volume regenerated in the distal 2 mm was associated significantly with DBD-depth reduction (r = 0.74, P < 0.001)., Conclusions: Bone volume regenerated in the distal 2 mm of the M2M denoted stability of distal periodontal healing of the M2M. DBD depth at baseline was the most influential factor for healing of a DBD of the M2M after M3M coronectomy. The remaining enamel and a small retromolar space could contribute to re-contact of the root complex and the M2M., Trial Registration: China Clinical Trial Center, ChiCTR1800014862 . Registered 10 February 2018.

Objective: To evaluate the accuracy and feasibility of a custom robot system guided by optical navigation for needle puncture on trigeminal gasserian ganglion., Methods: A synthetic human skull model was used, with plasticine placed around the skull base to imitate the human soft tissue. Cone beam CT (CBCT) scanning was performed before the operation. With image data transferred to the graphical user interface of the computer workstation, the oval foramen was selected as the target and the "skin entry point" was also determined by the surgeon on the surgical planning software. Thus the needle trajectory was eventually planned. The skull model was fixed firmly to the trial table with a head clamp and relative size of the trial table was the same as a standard operating table. Following point-based registration, the data were sent to the robot control unit. Only after the surgeon's confirmation, the needle was automatically inserted into the intended target by the robot guided by optical navigation. When the procedure was completed, the instantaneous data of the needle tip orientation acquired by navigation system was sent back to the computer workstation for accuracy verification by calculating the geometric distance between the needle tip and the planning target after matrix transformation. Subsequently, after the needle had been released, CBCT scanning was also acquired to make image fusion of the preoperative skull and the postoperative skull. The data of the needle tip orientation was acquired on the postoperative image and the accuracy was re-verified by calculating the geometric distance between the needle tip and the planning target after matrix transformation. IBM SPSS Statistics 20 was used for statistical analysis and the paired t-test was used to compare the differences in the accuracy measured by the intraoperative navigation and postoperative image fusion., Results: All 20 interventions were successfully located in oval foramen at the first needle insertion. The mean deviation of the needle tip was (0.56±0.07) mm (measured by the navigation system) and (1.49±0.14) mm (measured by the image fusion), respectively (P<0.001)., Conclusion: The experimental results show the robot system is efficient and reliable. The navigation accuracy is one of the most significant factors in robotic procedures.

Objective: To evaluate the diagnostic performance of a non-invasive, non-radiating, economical and convenient infrared thermal imaging in the detection of oral squamous cell carcinoma (OSCC) cervical lymph node metastasis, and evaluate its applicability via parallel test and series test., Methods: This study was a prospective clinical study which passed the ethical review by the Biomedical Ethics Committee, Hospital of Stomatology, Peking University, and had been submitted for clinical trial registration. Totally 74 OSCC patients who were to undergo a neck dissection were included in this study. The inclusion criteria were patients who: (1) were pathologically diagnosed as malignant tumors and planned to undergo surgical treatment including neck dissection; (2) agreed to participate in this study. The exclusion criteria were those who: (1) had undergone surgeries at head and neck previously; (2) with a history of systemic tumor adjuvant therapies such as radiotherapy or chemotherapy etc; (3) were unwilling or unable to cooperate. Basal information as well as clinical examination results were collected, such as physical examination and contradictive enhanced CT. Besides, infrared thermal imaging was done ahead of surgery. Analysis of the diagnostic power of infrared thermal imaging followed the principles of diagnostic test. The positive signs of infrared thermal imaging were: (1) asymmetric thermographic pattern including vascular pattern in ROI; (2) thickening image of unilateral facial artery/vein, submental artery/vein or external carotid artery; (3) surface temperature of ROI raised over 1 °C compared with the opposite side; (4) changes of neck profile with abnormal temperature pattern. The gold standard of this diagnostic test was pathology diagnosis of cervical lymph nodes., Results: The sensitivity of infrared thermal imaging was 75.0%, while the specificity was 69.0%, accuracy was 71.6%, positive predictive value was 64.9% and negative predictive value was 78.4%. The sensitivity of parallel test which stood for the combination of infrared thermal imaging and conventional clinical examinations was 87.9% while the specificity of series test was 97.6%., Conclusion: Infrared thermal imaging is a promising non-invasive, non-radiating and economical tool in the detection of cervical lymph node metastasis from OSCC when combined with conventional pre-operative examination.

Objective: To study the clinical characteristics of mandibular movement and masticatory muscle function in preoperative and postoperative patients with unilateral mandibular tumors in the region of mandibular body and ramus by combining digital mandibular movement records with electromyography, and to preliminarily explore the relationship and mechanism between movement and masticatory muscle function., Methods: Six preoperative patients with tumor in unilateral body and ramus of mandible were included, and three postoperative patients with unilateral segmental resection and reconstruction of mandibular bone were included. The mandibular movement recording system and surface electromyography system were used to collect the movement trajectory of the patients' mandibular marginal movement and chewing movement, and the surface electromyography of bilateral masseter and temporalis was recorded concurrently. The surface electromyography of bilateral masseter and temporalis was collected when the patients were at relaxation and at maximal voluntary clenching (MVC). The motion trajectory was observed on the digital virtual model, and the motion amplitude and direction of mandibular marginal movements were analyzed. The characteristics of masticatory electromyogram (EMG) activity in affected and unaffected sides at relaxation, MVC and bilateral mastication were analyzed, and the asymmetry indexes and activity indexes were calculated., Results: The preoperative mean maximum opening of the patients was (35.20±6.87) mm. Three patients had mild mouth opening limitation, and all the patients' mouth opening trajectory was skewed to the affected side. During lateral movements, the mean range of motion of the affected side [(10.34±1.27) mm] and that of the healthy side [(6.94±2.41) mm] were significantly different. The maximum opening of the postoperative patients was (30.65±17.32) mm, and the mandibular marginal movement characteristics were consistent with those of the patients before surgery. During MVC in the preoperative patients, the median EMG activities of the masseter muscle [44.20 (5.70, 197.90) μV] and the temporalis muscle [42.15 (22.90, 155.00) μV] on the affected side were slightly lower than those of the masseter [45.60 (7.50, 235.40) μV] and the temporalis muscle [63.30 (44.10, 126.70) μV] on the healthy side. In the postoperative patients, individualized changes occurred. Some patients suffered from weakened electromyographic activity on the affected side, while some other ones showed hyperelectromyographic activity on the affected side., Conclusion: Both benign and malignant tumors as well as their surgery can cause abnormal mandibular movements and change of electromyographic activity of bilateral masseter and temporalis muscles.

Objective: To explore the value of incorporated multimodal image fusion technology with computer-aided design of the skull base-infratemporal tumor treatment., Methods: A retrospective study was carried out to enroll seventeen patients with skull base-infratemporal tumors treated at Peking University Hospital of Stomatology from February 2011 to September 2018. Plain CT, enhanced CT and MRI data were imported into the iPlan 3.0 software (BrainLab navigation system), and the image fusion was performed for each patient preoperatively. Then the three-dimensional images of the tumor, vital vessels and craniofacial bones were reconstructed to prepare virtual operation design. We evaluated the application of multimodal image fusion technology that had been incorporated with computer-aided planning during the navigation-guided biopsy or surgery, through the analysis of the biopsy and operation data and regular follow-up postoperatively., Results: The mean age of 17 patients (7 males and 10 females) was 46 years. Primary tumors occurred in 11 cases, and recurrent tumors in 6 cases. The size of the 17 tumors ranged from 2.9 cm to 9 cm, and the mean size was 4.35 cm. There were 7 cases with skull base bone destruction and/or intracranial extension, and 10 cases with tumors adjacent to the skull base. High-quality multimodal fused images were obtained in all the 17 cases. The spatial-position relationships of the tumors, adjacent craniomaxillofacial bones and vital vessels labeled with different colors were displayed well on the generated fusion images. The multimodal image fusion technology that incorporated with computer-aided three-dimensional reconstruction and then applied in navigation-guided biopsy or surgery showed that, preoperative analysis and virtual operation design functioned with good results, especially in cases with small tumor size, recurrence or illdefined borders in the skull base-infratemporal region. Operation was carried out in 16 cases after preoperative diagnosis and assessment, and 1 case was performed by navigation-guided biopsy only. The proportions of navigation-guided surgery and biopsy were 70.6% (12/17) and 17.6% (3/17) individually. The positive rate of pathologic diagnosis using navigation-guided biopsy was 100% (3/3). All the navigation-guided biopsies or operations were carried out successfully. Complications included 1 case of cerebrospinal fluid leak from a recurred meningioma patient postoperatively, and 1 case of facial paralysis resulting from parotid-gland deep lobe tumor. Most (14/15) tumors got complete removal with safe boundary through intra-operative navigation verification and post-operative imaging confirmation, except for one case of subtotal resection to avoid the injury of cavernous sinus. The pathological results of the tumors could be classified to mesenchymal (10), adenogenous (3), neurogenic (3) or epithelial (1) resources. The follow-up time ranged from 3 to 94 months, with the median follow-up time of 9 months., Conclusion: Taking full advantages of individualized multimodal images, could help analyze the three-dimensional spatial position relationship of tumors, vital vessels and craniofacial bones properly, and then complete the virtual operation design well. The incorporated multimodal image fusion technology with navigation technology may improve the accuracy and safety of core needle biopsy and surgical treatment of skull base-infratemporal tumors.

Fabrics are widely applied in various fields, such as body armor, aerospace industry and military equipment. This paper reports the semi-blunt puncture behavior of fabrics impregnated with a shear thickening fluid (STF), which is a dispersion system of nano silica/polyethylene glycol (SiO 2 /PEG). The rheological properties and microstructure of the STF were tested to evaluate the influence of SiO 2 particle size and additives (graphene nanoplatelets) on the puncture behavior of the final fabrics. The surface characteristics of neat and STF-treated fabrics were separately measured by field emission scanning electron microscopy (FESEM), which helps study the damage morphology and mechanism of the fabric. The surface characteristics of the silica nanoparticles and additives were also measured by transmission electron microscopy (TEM). The results demonstrated that the puncture behavior of the woven fabric was significantly enhanced due to the presence of STF. Moreover, the presence of additive GNPs induced a relatively lower shear thickening phenomenon, while a significant enhancement in the semi-blunt puncture behavior of the woven fabric was observed., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives  This study aims to evaluate the feasibility of a custom robot system guided by optical cone beam computed tomography (CBCT)-based navigation for skull base biopsy. Design  An accuracy study was conducted. Setting  Platform for navigation and robot-aided surgery technology. Participants  Phantom skull. Main Outcome Measures  The primary outcome measure was to investigate the accuracy of robot-assisted needle biopsy for skull base tumors. A 14-gauge needle was automatically inserted by the five degrees of freedom robot into the intended target, guided by optical navigation. The result was displayed on the graphical user interface after matrix transformation. Postoperative image scanning was performed, and the result was verified with image fusion. Results  All 20 interventions were successfully performed. The mean deviation of the needle tip was 0.56 ± 0.22 mm (measured by the navigation system) versus 1.73 ± 0.60 mm (measured by image fusion) ( p  < 0.05). The mean insertion depth was 52.3 mm (range: 49.7-55.2 mm). The mean angular deviations off the x-axis, y-axis, and z-axis were 1.51 ± 0.67, 2.33 ± 1.65, and 1.47 ± 1.16 degrees, respectively. Conclusions  The experimental results show the robot system is efficient, reliable, and safe. The navigation accuracy is a significant factor in robotic procedures.

There are numerous clinical cases indicating that long-term use of bevacizumab may increase the invasiveness of tumors. However, to date, little is known about underlying molecular mechanisms. Therefore, the purpose of our study was to investigate effects of bevacizumab in four cancer cells lines (WSU-HN6, CAL27, Tca83, and HeLa). It was found to promote migration and invasion in the WSU-HN6 and Tca83 cases, while exerting inhibitory effects in CAL27 and HeLa cells. The signal transducer and activator of transcription (STAT) 3 inhibitors niclosamide and S3I-201 inhibited the STAT3 signal pathway, which is activated by bevacizumab. These inhibitors also substantially blocked bevacizumab-induced migration of WSU-HN6 and Tca83 cells. Bevacizumab upregulated interleukin (IL)-6 and phosphorylated (p)-STAT3 expression time-dependently. Therefore, we propose that bevacizumab has differential effects on the migration of different cancer cell lines and promotes migration via the IL-6/STAT3 signaling pathway.

The purpose of this study is to establish in vivo and in vitro models for studying lymphatic metastasis of squamous cell carcinoma (SCC). Three cell lines CAL-27, Tca-83, and HeLa were injected into the tongue of nude mice. Forty days after injection, we could isolate cells of 2 homologous cell lines LN-CAL-27 and LN-HeLa from lymph node metastasis lesions. Then, the homologous cell pairs were compared by the CCK-8 assay, wound healing assay, real-time PCR, western blot, and animal experiments. The results showed that all the three cell lines could be used to establish lymphatic metastasis animal models, and the lymphatic metastasis process was observed clearly. In addition, the homologous cell pairs performed differently from parent lines with respect to biological behavior and lymphatic metastasis-related gene and protein expression. In conclusion, CAL-27, Tca-83, and HeLa cells could be used to simulate the lymphatic metastasis process of oral cancer in vivo. Furthermore, the homologous cell pairs (CAL-27 and LN-CAL-27; HeLa and LN-HeLa) are potential tools for in vitro investigation of the mechanisms underlying metastasis.

In the title compound, C(33)H(38)N(4)O(3), the mean planes of the 9H-xanthene unit and spiro-lactam (nine-atom) core are almost mutually perpendicular at 87.26 (6)°. Intra-molecular N-H⋯O and C-H⋯N inter-actions influence the 4-oxo-pent-2-en-2-yl-amino conformation. In the crystal, weak C-H⋯O hydrogen bonds link the mol-ecules into chains along [001].

Aim: To investigate the role of 64-slice computed tomography (CT) in portal vein cavernous transformation to determine surgical strategy., Methods: The site of lesions and extent of collateral circulation in 12 pediatric cases of cavernous transformation of the portal vein with surgical treatment were analyzed., Results: Eleven of 12 children had esophageal varices and were treated with lower esophageal and gastric devascularization and splenectomy, and the other case was only treated with splenectomy. There were eight cases with spontaneous spleen/stomach-renal shunt, four with Retzius vein opening, which was reserved during surgery. Three cases of lesions involving the intrahepatic portal vein (PV) were treated with living donor liver transplantation. One patient died from PV thrombosis after liver transplantation, and the rest had no significant complications., Conclusion: The PV, its branches and collateral circulation were clearly seen by 64-slice spiral CT angiography, which helped with preoperative surgical planning.

Background: Trans-sacral axial L5/S1 interbody fusion (AxiaLIF), a novel surgical procedure, recently adopted in clinical practice, has excellent clinical outcomes. However, there is inadequate data on the feasibility of the approach in all adult patients and the optimal surgical approach is currently unclear; therefore, further studies are required. In order to enhance the surgical approach for AxiaLIF, prospective anatomical imaging optimization is necessary. The objective of this study was to investigate the ability of magnetic resonance imaging (MRI) to achieve an optimal procedural setting., Methods: The subjects (n=40) underwent lumbosacral MRI examination. The median sagittal MRI images were analyzed and four measurement markers were defined as follows: the center of the L5/S1 disc (A), the anterior margin of the S1/2 disc space (B), the sacrococcygeal junction (C), and the coccygeal tip (D). The measurement markers were connected to each other to produce five lines (AB, AC, AD, BC, and BD), as reference lines for surgical approaches. The distance between each reference line and the anterior and posterior margins of the L5 and S1 vertebral bodies was measured to determine the safety of the respective approaches., Results: In all patients, Lines AB and AC satisfied the imaging safety criteria. Line AB would result in a significant deviation from the median and was determined to be unsuitable for AxiaLIF. Line AD satisfied the imaging safety criteria in 39 patients. However, the anal proximity of the puncture point proved to be limiting. For lines BC and BD, the imaging safety criteria were satisfied in 70% and 45% of patients, respectively., Conclusions: The AxiaLIF procedure is a safe technique for insertion of fusion implants in all subjects. Line AC is a favorable reference line for surgical approach and safe for all subjects, while line BC is not suitable for all subjects.

In the title compound, C(22)H(23)FN(2)OS, the piperidine ring shows chair confirmation and the two benzene rings make a dihedral angle of 17.0 (6)°. The thia-zole fragment is essentially planar with an r.m.s. deviation of 0.004 (2) Å and a maximum deviation of 0.006 (2) Å.. In the crystal, inter-molecular C-H⋯π inter-actions lead to the formation of a layer structure.

Background: Previous clinical and basic research of axial lumbar interbody fusion (AxiaLIF) all focused on the L5/S1. However, there is no data on the feasibility of this approach for the fusion of both L4/5 and L5/S1. This study aimed to explore whether transsacral axial interbody fusion is a candidate for the fusion of both L4/5 and L5/S1., Methods: The subjects (n = 40) underwent lumbosacral magnetic resonance imaging (MRI). The median sagittal MRI images were analyzed and five measurement markers were defined as follows: the center of the L4/5 disc (A), the center of the L5/S1 disc (B), the anterior margin of the S1/2 space (C), the sacrococcygeal junction (D), and the coccygeal tip (E). The measurement markers were connected each other to produce nine lines (AB, AC, AD, AE, BC, BD, BE, CD and CE) as the reference lines for surgical approaches. The distance between each reference line and the anterior and posterior margins of the L4, L5 and S1 vertebral bodies were measured to determine the safety of the respective approaches., Results: Twenty subjects were capable of finding one reference line to fuse both L4/5 and L5/S1 via transsacral axial interbody fusion approach. The surgical approach reference line was AE or CE line. In the other 20 subjects, it was failed to find a reference line which met the safety criteria for fusing both L4/5 and L5/S1., Conclusions: About half of subjects were capable of finding a suitable AxiaLIF reference line to fuse both L4/5 and L5/S1. In some subjects, it was difficult to find a suitable AxiaLIF reference line to fuse both L4/5 and L5/S1.

Objective: Activation of hedgehog (Hh) pathway has been implicated in the development of human malignancies. Hh as well as related downstream target genes has been extensively studied in many kinds of malignant tumours for clinical diagnostic or prognostic utilities. This study aimed at investigating whether Hh molecules provides a molecular marker of hepatoblastoma malignancy., Methods: We obtained tissue sections from 32 patients with hepatoblastoma as well as cholestasis and normal control. Immunohistochemical analysis were performed to determine Hh signal components in human hepatoblastoma. The prognostic significance of single expression of Hh signal components were evaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis for statistical analysis., Results: Expression of Hh signal components showed an increase in hepatoblastoma compared with cholestasis and normal tissues. There was a positive correlation between Smo or Gli1 expression and tumor clinicopathological features, such as histological type, tumor grade, tumor size and clinical stage. Both Smo or Gli1 protein high expression was significantly associated with poor prognosis by univariate analyses and multivariate analyses., Conclusions: Abnormal Hh signaling activation plays important roles in the malignant potential of hepatoblastoma. Gli1 expression is an independent prognostic marker.

Aim: To assess the effect of human leukocyte antigen (HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies., Methods: Articles in PubMed/MEDLINE, EMBASE and the Cochrane database from January 1970 to June 2009, including non-English literature identified in these databases, were searched. Only studies comparing HLA or sub-phenotype matching with mismatching were extracted. The percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed. A meta-analysis was performed when at least 3 studies provided data., Results: Sixteen studies met the inclusion criteria. A lower number of HLA mismatches (0-2 vs 3-6) did reduce the incidence of acute rejection (relative risk: 0.77, P = 0.03). The degree of HLA mismatching (0-2 vs 3-6) had no significant effect on 1-year [hazard ratio (HR): 1.04, P = 0.68] and 5-year (HR: 1.09, P = 0.38) graft survival. In sub-phenotype analysis, the degree of HLA-A, B and DR mismatching (0 vs 1-2) had no significant effect on 1-year and 5-year graft survival, either. The HRs and P-values were 0.95, 0.71 (HLA-A, 1-year); 1.06, 0.60 (HLA-A, 5-year); 0.77, 0.16 (HLA-B, 1-year); 1.07, 0.56 (HLA-DR, 1-year); 1.18, 0.23 (HLA-DR, 5-year), respectively., Conclusion: The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft outcomes. To obtain a short recovery time and minimize rejection post transplantation, HLA matching studies should be considered before the operation.

Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant tumor in the head and neck region, comprising more than 90% of all oral malignancies. A feasible approach for an animal model to study OSCC lymph node metastasis was established and biological behaviors of three oral squamous cell carcinoma cell lines were compared., Methods: After implanting three kinds of cell lines (GDC185, Tca8113, Tca83) into three different anatomical sites in nude mice, namely the tongue, floor of the mouth, and axillary fossa, we observed the tumorigenicity and the metastatic capacity, which was confirmed by histopathology under a surgical microscope., Results: The animal model injected with GDC185 cells into the floor of the mouth had the highest rate of neck lymph node metastasis (55.6%) and the cell lines had significantly different biological behaviors., Conclusions: Nude mice injected with GDC185 cells into the floor of the mouth could be used as a feasible animal model to study neck metastasis of oral squamous cell carcinoma.

We examined whether low dose radiation (LDR) exposure (75 mGy) could increase the therapeutic efficacy of cyclophosphamide (CTX) by comparing the effects of tumor suppression, tumor cell apoptosis, cell cycle and proliferation of bone marrow in vivo. Kunming mice implanted with S(180) sarcoma cells were given 75 mGy whole body gamma-ray radiation exposure and CTX (300 mg/kg) by intraperitoneal injection 36 hours after LDR. Proliferation of bone marrow and tumor cells was analyzed by flow cytometry. Cytochrome c leakage from the tumor was measured by Western-blot. We discovered that tumor growth was significantly reduced in the group exposed to CTX add to LDR. The apoptosis of tumor cells increased significantly after LDR. The tumor cells were arrested in G(1) phase in the groups treated with CTX and CTX + LDR, but cell cycle was more significantly arrested in mice exposed to LDR followed by CTX than in mice exposed only to LDR or CTX chemotherapy. Concentration of bone marrow cells and proliferation index in CTX + LDR mice were higher than those in the untreated mice. LDR or CTX + LDR could induce greater cytochrome c levels and caspase-3 activity in tumors. These results suggest that low dose radiation can enhance the anti-tumor effect of the chemotherapy agent CTX markedly. Furthermore, LDR significantly protects hematopoetic function of the bone marrow, which is of practical significance on adjuvant chemotherapy.

Background: Resection of tumors arising from the tongue base and the parapharyngeal space is difficult for exposure and manipulation because of their obscure location. The aim of this study was to evaluate the surgical approach of the pre-mental foramen mandibulotomy for resecting the tumors of tongue base and parapharyngeal space., Methods: Fifty-one patients with tumors of tongue base and parapharyngeal space were treated using the mandibulotomy approach on the pre-mental foramen. In the present study, this technique was described in detail. The patients were followed up for three months to six years with a mean of 26 months., Results: The tumors of tongue base and parapharyngeal space could be exposed clearly and be resected radically by surgical approach of pre-mental foramen mandibulotomy. The surgical complications were reduced., Conclusions: Compared to other surgical approaches, such as lateral mandibulotomy, midline mandibulotomy, the suprahyoid parapharyngeal approach, and paramedian mandibulotomy, we found that the pre-mental foramen mandibulotomy is the ideal choice for resecting the tumors of tongue base and parapharyngeal space.

We introduced a new method for reconstruction of accessory nerve defects by using the sternocleidomastoid muscle (SCM)-great auricular nerve flap. Thirty-four patients receiving traditional radical neck dissection were divided into two groups: the accessory nerve not-reconstructed group (Group A, N = 19) and the accessory nerve reconstructed group (Group B, n = 15). The surgical procedure of the reconstruction is described in detail. Postoperative shoulder functions were compared between the two groups. We found that Group B experienced much better shoulder function recovery than Group A. Both groups had good wound healing. It is concluded that reconstruction of accessory nerve defects with SCM-great auricular nerve flap is simple, effective and complication-free and worthwhile.

Aim: To investigate whether acute lung injury (ALI) in ventilated piglets with bacterial infection affects NF-kappaB and AP-1 expression in alveolar macrophages (AM) and whether nitric oxide (NO), surfactant (Surf), glucocorticoids (GC) affect NF-kappaB and AP-1 activation in AM in vivo and in vitro., Methods: The animals were intraperitoneally injected Escherichia coli, which caused ALI. Nuclear extracts of AM were analyzed by electrophoretic mobility shift assay (EMSA) for the nuclear factor-kappa B (NF-kappaB) and activation protein-1 (AP-1) expression. Detection of IkappaB-alpha protein was from cytoplasmic extract by Western blotting. Immunocytochemistry staining was used for intracellular location of p65 subunits of NF-kappaB., Results: In ex vivo experiments, strikingly higher expression of NF-kappaB and AP-1 by EMSA was found 6 h after bacterial injection in contrast to the Normal group. In the NO, SNO, and GC groups, markedly attenuated NF-kappaB and AP-1 activation was observed. The NF-kappaB and AP-1 activation in Surf group showed lower levels of the expression. Immunoblotting of AM cytoplasmic extract showed low expression of IkappaB-alphaprotein in the Control and Surf groups. The stronger expression was observed in the NO, GC, and SNO groups. AM of the Control and Surf groups showed intense nuclear staining, with decreased nuclear staining in the NO, GC and SNO groups. In in vitro experiment, it caused a significant increase in NF-kappaB and AP-1 activity in AM 1 h after exposure to lipopolysaccharides (LPS). In AM treated by LPS+SNP and LPS+GC, all showed decrease of DNA binding activity of NF-kappaB and AP-1 compared to those exposed to LPS+Surf. Immunoblotting of AM cytoplasmic extract showed that LPS stimulation of AM resulted in the low expression of IkappaB-alpha protein, which was not observed in the presence of SNP and methylprednisolone. However, the surfactant did not show such effect. LPS+Surf-exposed AM had intense nuclear staining, whereas decreased nuclear staining in the LPS+NO and LPS+GC-treated cultures was found, confirming a decrease in NF-kappaB activity., Conclusion: Activation of NF-kappaB was found in AM of ventilated piglets with bacterial ALI. NO and GS could prevent NF-kappaB and AP-1 activation in vivo and in vitro. Surfactant has limited effects on NF-kappaB and AP-1 activity.