Morphometric analysis of paired fibula and mandible for optimal fibular mandibular reconstruction in a Chinese population.

To analyze the morphology of paired fibula and mandible aiming to choose optimal fibular segments for mandibular reconstruction in a Chinses population. A total of 118 cases of paired mandible and fibula was collected. All patients were received preoperative cone beam CT (CBCT) scans for mandibular evaluation and CT-angiographical (CTA) examination of the bilateral lower legs, respectively. The cross-sectional morphological differences between proximal (Side P), middle (Side M) and distal (Side D) segments of fibula and anterior, premolar and molar areas of mandible were compared. The most frequent cross-sectional shape at Side D, Side M and Side P portion of fibula was circular (75.4%), triangular (67.8%) and circular (49.2%), respectively. In anterior, premolar and molar areas of mandible, the most of the cross-section was s-shape (90.82%), straight (83.64%) and oblique (91.89%), respectively. The height and width of upper one third (W1) at Side M were significantly larger than those of Side D and Side P (p < 0.0001). There was significantly difference of width of lower one third (W2) among three groups (p < 0.0001). As for the height and widths of mandible, there was significant difference among anterior, premolar and molar regions (p < 0.0001). The rate of height between Side M of fibula and mandible (H (Side M/area)) was significantly larger than H (Side D/area) and H (Side P/area) (p < 0.01). The ratio of W1 between Side D of fibula and mandible (W1 (Side D/area)) was significantly larger than that of W1 (Side M/area) and W1 (side P/area) (p < 0.05). As for the ratio of W2 between fibula and mandible (W2 (plane/area)), there was significant difference among groups (p < 0.01). The distal and middle segments of fibula were suitable for reconstructing the anterior area of mandible and the proximal segment of fibula was more compatible with the premolar and molar areas of mandible.Clinical Relevance Presurgical morphometric analysis of paired fibula and mandible aids for optimal fibular-based mandibular reconstruction.

Immune landscape and subtypes in primary resectable oral squamous cell carcinoma: prognostic significance and predictive of therapeutic response.

BACKGROUND: Immune landscape of cancer has been increasingly recognized as a key feature affecting disease progression, prognosis and therapeutic response. Here, we sought to comprehensively characterize the patterns of tumor-infiltrating immune cells (TIIs) in primary oral squamous cell carcinoma (OSCC) and develop immune features-derived models for prognostication and therapeutic prediction. METHODS: A total number of 392 patients with OSCC receiving ablative surgery at three independent centers were retrospectively enrolled and defined as training, testing and validation cohorts. Detailed features of 12 types of TIIs at center of tumor and invasive margin were assessed by immunohistochemistry coupled with digital quantification. TIIs abundance in OSCC was also estimated by bioinformatics approaches using multiple publicly available data sets. Prognostic models based on selected immune features were trained via machine learning approach, validated in independent cohorts and evaluated by time-dependent area under the curves and concordance index (C-index). Immune types of OSCC were further identified by consensus clustering and their associations with genetic, molecular features and patient survival were clarified. RESULTS: Patterns of TIIs infiltration varied among patients and dynamically evolved along with tumor progression. Prognostic models based on selected TIIs were identified as efficient and sensitive biomarkers to stratify patients into subgroups with favorable or inferior survival as well as responders or non-responders to postoperative radiotherapy or immunotherapy. These models outperformed multiple conventional biomarkers and immune-related scores in prognostic prediction. Furthermore, we identified two main immune subtypes of OSCC (immune-hot and immune-cold) which harbored characteristic TIIs infiltrations and genomic and molecular features, and associated with patient survival. CONCLUSIONS: Our results delineated immune landscape and subtypes in OSCC, consolidated their clinical values as robust biomarkers to predict patient survival and therapeutic benefits and reinforced key roles of TIIs and tumor-immune interactions underlying oral tumorigenesis, ultimately facilitating development of tailed immunotherapeutic strategies.

A Novel Classification of Relationship Between Nasal Septum and Inferior Turbinate Associated With Nasal Airway Obstruction in Patients With Unilateral Alveolar Cleft.

OBJECTIVE: This study aims to investigate nasal morphologies associated with nasal airway obstruction in unilateral alveolar cleft patients. METHODS: A total of 234 unilateral alveolar cleft cases were performed cone beam computed tomography scans. The digital imaging and communication in medicine data were imported into Simplant Pro software. The radiographic features including nasal septum deviation and inferior turbinate hypertrophy as well as nasal airway volume and sinusitis were analyzed. RESULTS: A new radiographic classification of relationship between nasal septum and inferior turbinate (NS-IT) on the cleft side was proposed and three types of NS-IT relationship (type I, II and III) were identified in 234 cases. The statistical analysis revealed that the nasal airway volume on non-cleft side was significantly higher than that on cleft side in each of three types (P  < 0.0001), while no difference of nasal airway volume on non-cleft side was found among three types. In addition, the nasal airway volume on non-cleft side in type I and II was significantly higher than that in type III (P < 0.0001). Also, type III presented higher rate of maxillary sinusitis (P = 0.0154) and ethmoid sinusitis on cleft side (P = 0.0490) than type I and II. The other indexes including clinical variances were not significant among three types. CONCLUSIONS: Unilateral alveolar cleft patients with type III NS-IT relationship could have nasal airway obstruction and higher rate of maxillary and ethmoid sinusitis on cleft side, which may be taken into account at primary cleft repair and alveolar bone grafting treatment.

Comparison of Anatomical Features of Alveolar Cleft in Unilateral Cleft Lip and Palate Patients of Different Ages.

OBJECTIVES: This study aimed to compare the anatomical features of alveolar cleft in patients with complete unilateral cleft lip and palate (UCLP) of different ages. METHODS: Sixty UCLP patients were divided into 3 groups as follows: group 1 (7-12 years old), group 2 (13-18 years old) and group 3 (more than 18 years old). The radiographic images were analyzed based on cone beam computed tomography (CBCT) images. RESULTS: The mean age in 3 groups was 10.45 ±â€Š1.15, 15.05 ±â€Š1.90, and 22.55 ±â€Š3.00 years (P < 0.0001). The lip-palatal width in Group 2 and 3 was 15.14 ±â€Š3.67 mm and 15.50 ±â€Š3.92 mm, which was significantly larger than 12.97 ±â€Š1.82 mm in Group 1 (P = 0.037). The volume of alveolar defect was 1.09 ±â€Š0.23 cm, 1.28 ±â€Š0.38 cm and 1.40 ±â€Š0.58 cm in 3 groups, and the difference between any 2 of them was significant (P = 0.0004). The prevalence of ipsilateral but contralateral maxillary sinusitis was significant among 3 groups (P = 0.0015) while the other nasal deformities including nasal septum deviation and inferior turbinate hypertrophy was not found significant. CONCLUSIONS: Alveolar cleft volume increased with age, which is properly due to enlarged width of lip-palatal defect. The significant higher frequencies of ipsilateral maxillary sinusitis in patients under 18 could increase the risk of bone infection.

Quantitative sensory testing of periauricular skin in healthy adults.

The aim of this study was to investigate the test-retest reliability of quantitative sensory testing (QST) and mechanical sensitivity mapping of the periauricular skin. Twenty volunteers (10 men, 10 women) participated in two sessions at intervals of one week. Cold and warm detection threshold (CDT&WDT), cold and heat pain threshold (CPT&HPT), mechanical detection and pain threshold (MDT&MPT), pressure pain threshold (PPT) and two-point discrimination (2PD) were measured at five sites: bilateral subauricular and postauricular sites (LA, RA, LB, RB) and the dorsum of left hand (control). Pressure stimulation was applied at each of the four periauricular test sites. The test-retest reliability of the QST data implied fair to excellent agreement as evaluated by the intra-class correlation coefficients (ICC; all >0.4) for different days. There was no difference between each side in the QST parameters and mechanical sensitivity mapping (P ≥ 0.057). Significant differences between subauricular and postauricular sites were shown for WDT and PPT (P ≤ 0.028). NRS scores of mechanical sensitivity mapping showed significant effects of gender, site and point (P ≤ 0.040). QST and mechanical sensitivity mapping can be considered to be a reliable technique to assess somatosensory function of the periauricular skin.

Single-stage repair of secondary unilateral cleft lip-nose deformity in adults.

Correction of cleft lip-nose deformity in adult patients is different from that in children. One-stage correction has proved to be a suitable technique for patients with cleft-lip nose deformity. This study aimed to explore a particular single-stage method and evaluate the effect of simultaneous reparation of secondary unilateral cleft lip-nose deformities. Cleft lip patients who had previously undergone nasolabial surgery with residual poor nasal/lip appearance were included. The alveolar bone defect was repaired with granular costal cortical bone. Lip revision and rhinoplasty were performed using diced costal cartilage. The lip, nose, and alveolar deformities were corrected in one stage. From 2011 to 2017, 53 cases were treated. The vermilion discrepancy was corrected in all cases. Fifty-one patients were successfully treated, with primary healing in the bony recipient area. Cancellous bone exposure occurred in two cases. The wounds were healed after debridement and drainage. Appearances were improved in all patients. The mean change in columella-labial angle ranged from 82.50 to 92.78° (p < 0.001). This one-stage correction appears to have led to a distinct improvement in the nasal tip projection and lip. The method is considered to be effective and reliable in patients with secondary unilateral cleft lip-nose deformities.

Comparative Outcomes of Block and Cancellous Iliac Bone Grafting in Older Unilateral Alveolar Cleft Patients.

OBJECTIVE: To compare osseous outcomes of block and cancellous iliac bone grafting in older unilateral alveolar cleft patients. DESIGN: Retrospective and observational follow-up study. SETTING: Cleft Lip and Palate Centre, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China. PATIENTS: Forty-five nonsyndromic patients with unilateral complete alveolar cleft were enrolled in this study (25 patients in block bone graft group and 20 patients in cancellous bone graft group). INTERVENTIONS: In cancellous bone graft group, the alveolar cleft was filled with iliac cancellous bone particulate. In group of block bone graft, the harvested bone block was trimmed and fixed in alveolar defect. MAIN OUTCOME MEASURES: A novel method was proposed to investigate the volume and density of residual bone graft at 1-week, 3- and 6-month, 1- and 2-year postoperatively based on cone beam computed tomography scans. RESULTS: No difference in bone graft volume was found between 2 groups at 1-week and 3-month postoperatively; however, the residual volume of block bone graft group was significantly larger than that of cancellous bone graft group at 6-month, 1- and 2-year postoperatively. The bone density of block bone graft group was lower at 1-week and 3-month postoperatively but was comparable at 6-month, 1- and 2-year postoperatively. Our method was reliable and accurate to identify the range of residual bone graft when the boundary of grafted bone could not be identified clearly. CONCLUSION: Block bone graft could achieve comparable bone density and retain a greater amount of residual bone comparing to cancellous bone graft.

Biological Response to Recombinant Human Bone Morphogenetic Protein-2 on Bone-Implant Osseointegration in Ovariectomized Experimental Design.

OBJECTIVE: The aim of this study is to investigate the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone-implant osteointegration in osteoporotic rats. MATERIALS AND METHODS: Thirty-six female Wistar rats were randomly divided into 3 groups: sham-operation (SHAM), ovariectomized (OVX), and ovariectomized with rhBMP-2 (OVX + rhBMP-2). The bone density of right tibia was observed with x-ray and the serum alkaline phosphatase (ALP) activity was measured preovariectomy and postovariectomy using an ALP-kit. In OVX + rhBMP-2 group, rhBMP-2 was embedded in the peri-implant area, while SHAM and OVX groups did not contain rhBMP-2. Four and eight weeks after implantation, the rats were killed and the right tibia with implants was taken by x-ray. Histologic changes were investigated by hematoxylin and eosin staining, scanning electron microscope (SEM), and energy dispersive spectrometer examinations. RESULTS: The serum ALP level was significantly higher in ovariectomized rats compared with that before ovariectomy (P < 0.05), while no difference was found in SHAM rats. At 12 weeks after ovariectomy, radiographic and histologic findings showed significant osteoporotic changes in proximal tibial metaphyses of OVX rats, including reduced cortical bone density and enlargement of bone marrow cavity compared with SHAM ones. The results of implantation verified new bone formation around implants in OVX + rhBMP-2 and SHAM groups, indicating favorable bone healing and osseointegration. No bone resorption was found in OVX + rhBMP-2 group, while some soft tissue was observed in bone-implant interface in SHAM group. In OVX group, there was no effective bone-implant osseointegration and mature bone formed around implants, and some implants were even lost due to chronic inflammation. The percentage of calcium and phosphorous atoms was significantly higher and the percentage of sulfur element was significantly lower in peri-implant area in OVX + rhBMP-2 and SHAM groups than that in OVX group. CONCLUSION: rhBMP-2 could enhance the osseous healing and restore bone-implant osseointegration in osteoporotic rats.

Effect of Navigation System on Removal of Foreign Bodies in Head and Neck Surgery.

Foreign bodies retained in oral and maxillofacial regions include different types and properties. Road traffic accident is one of the major causes of the maxillofacial trauma. Foreign bodies can cause direct or indirect damage to the body, even life-threatening. It is a demanding procedure to detect the accurate position and implement surgical removal of the embedded fragments in the soft tissue in clinic.Usually, foreign bodies are close to important structures such as the head and neck region with limited intraoperative visibility and anatomical intricacies. Therefore, the key to remove foreign bodies in head and neck surgery is precise localization and reasonable surgical approaches. The authors reported that the foreign bodies adjacent to large vessels in a case were successfully removed assisted by AccuNavi-A surgical navigation system.

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.

Anatomical Study and Clinical Application of Facial Artery Perforator Flaps in Intraoral Reconstruction: Focusing on Venous System.

PURPOSE: Facial artery perforator flaps (FAPFs) are preferred for the repair of intraoral and peri-nasal defects because it is a convenient procedure with minimal donor-site morbidity. The purpose of this study was to investigate the anatomic features of FAPFs and present their clinical application in intraoral reconstruction. MATERIALS AND METHODS: Five cadaver specimens (10 sides) of the head and neck region and 90 clinical cases (90 sides) of neck dissection were analyzed to explore the facial venous drainage system of FAPFs. In addition, anatomic features of the facial artery and vein and the marginal mandibular branch of the facial nerve were investigated in cadaver specimens. Furthermore, the authors reviewed a series of 33 intraoral reconstruction cases using their designed FAPFs focusing on flap survival and facial venous drainage system types. RESULTS: Based on cadaveric and clinical observations, the facial vein drainage system was divided into 3 types: type A drained into the internal jugular vein (47%); type B drained into the external jugular vein (37%); and type C drained into the anterior jugular vein (16%). The mean distances from the facial artery to the vein at the region of the FAPF pedicle and tip were 2.79 ± 0.51 and 10.24 ± 0.70 mm, respectively. Most cases using the authors' designed FAPFs yielded satisfactory esthetic and functional outcomes, whereas 3 cases presented with venous congestion from type C facial vein drainage. CONCLUSION: This study improved the understanding of the anatomic features and clinical application of FAPFs in intraoral reconstruction. This FAPF design could be used to achieve superior intraoral defect reconstruction, and type C facial vein drainage might be a risk factor for flap survival.

Computer-aided design-based preoperative planning of screw osteosynthesis for type B condylar head fractures: A preliminary study.

OBJECTIVE: To investigate the clinical application of a new computer-aided design - (CAD) based planning method for the treatment of type B condylar head fractures without fragmentation. METHODS: A total of 13 adult patients (19 sides) with type B condylar head fractures were included in the study. In all cases, imaging was performed using cone bean computed tomography (CBCT) preoperative, and Digital Imaging and Communications in Medicine (DICOM) files were imported into Simplant 11.04 software. The fracture of the mandibular condyle was reconstructed by a three-dimensional reconstruction module, and the simulation of reduction was achieved according to the morphological characteristics. Preoperative design was performed based on the CAD technology, and the three-dimensional interface was used to determine the length, location, and orientation of the positional screw. Osteosynthesis was performed with a single positional screw according to the optimum direction assessed in the preoperative planning CBCT, and the result was confirmed with postoperative CBCT scans and clinical follow-up. RESULTS: Preoperative computer-aided design was able to predict the length, location, and direction of the positional screw. Postoperative CBCT results demonstrated that 12 cases (18 sides) were consistent with preoperative design with exception of one case (one side) due to unexpected rupture of the fragment. Six-month follow-up showed the condylar fractures were anatomically repositioned and that healing was excellent in 12 cases (18 sides) with minor displacement and resorption in one case (one side). Postoperative occlusion in all cases was excellent, and the maximum mouth opening improved from mean 1.2 cm preoperatively to a of mean 4.3 cm at 6 months postoperatively. The data for mandibular movements at 6 months postoperatively demonstrated the recovery of protrusion, without higher grade limitations for laterotrusion. In one case, there appeared to be mandibular deviation (<0.5 cm) with mouth opening. CONCLUSION: The new preoperative design provides relevant data for screw osteosynthesis to enhance the precision and effectiveness of open reduction and internal fixation type B condylar head fractures.

Accurate Evaluation of Cone-Beam Computed Tomography to Volumetrically Assess Bone Grafting in Alveolar Cleft Patients.

OBJECTIVE: The aim of this study was to investigate the accuracy of cone-beam computed tomography (CBCT) to assess the volume of bone graft in alveolar cleft patients. MATERIALS AND METHODS: Twelve patients of unilateral alveolar cleft were included in this study. All patients were taken CBCT preoperative and 1 week postoperative. The digital imaging and communications in medicine (DICOM) files were imported into Simplant software and three-dimensional (3D) reconstruction of the alveolar defect was achieved. With 3D volumetric measurements module, the volume of alveolar cleft was calculated preoperatively. During operation, the syringe compression method was adopted to calculate the actual amount of bone graft. One week postoperative, CBCT scan was performed again to measure the bone volume grafted to the defect. The volumetric ratio of the syringe compression method to preoperative CBCT assessment and the volume difference between syringe compression method and postoperative CBCT assessment were analyzed to evaluate the accuracy of CBCT measurement. RESULTS: The 3D structure of the alveolar cleft and the boundary of bone graft was clear from CBCT images. The estimated volume of alveolar cleft by preoperative CBCT scans was 1.06 ±â€Š0.09 cm, and the actual amount of bone graft determined by the syringe compression method was 1.51 ±â€Š0.12 cm. The ratio between the latter to the former was 1.43 ±â€Š0.07. The calculated volume of bone graft by 1-week postoperative CBCT scans was 1.53 ±â€Š0.11 cm, with no significant difference compared with the actual amount of bone graft (P > 0.05). CONCLUSIONS: CBCT was an accurate measurement to calculate the volume of alveolar defect and bone graft in alveolar cleft patients. Preoperative scans could aid in quantitatively determining the bone amount needed to adequately fill the bone defect, and the postoperative scans give accurate follow-up evaluation after surgery.

[Clinical effect of functional repair of bilateral cleft lip in 66 patients].

PURPOSE: To explore the clinical effect of functional repair for bilateral cleft lip using modified Mulliken method. METHODS: Sixty-six patients with bilateral cleft lip were selected and assigned to receive modified Mulliken method. During the operation, the prolabium was kept as narrow "tie" shape, the orbicularis oris was anatomically repositioned, and the orbicularis oris ring was re-built. Vermilion tubercle was reconstructed with the lateral red vermillion. The nasal deformity was preliminarily repaired. and the nasal columella was elongated at the same time. RESULTS: All the patients were followed-up for 0.5-2 years, there was no "trisection upper lip". The symmetry and natural shape of Cupid's bow were obtained in more than 80% patients. The width of philtrum was similar to normal children. Full vermilion of the lips, moderate-size vermilion tubercles and good dynamic and static shape were obtained without whistle deformities. Normal width of nasal base and nostril symmetry were gained. The columella was elongated. Satisfactory contour of the nasal tip was achieved. CONCLUSIONS: Modified Mulliken method could functionally repair bilateral cleft lip and effectively correct nasolabial deformities. It is worthy of wide clinical application.

A new design of facial artery perforator flaps for the reconstruction of small- to medium-sized intraoral defects.

AIM: The aim of this study was to investigate the reliability and outcomes of a new design of facial artery perforator flaps, extending from the angle of the mouth to the border of the mandible, for the reconstruction of small- to medium-sized intraoral defects. PATIENTS AND METHODS: The technique had been used in 23 patients between February 2009 and August 2012. The locations of intraoral defects included the tongue, the floor of the mouth, the inferior gingival mucosa, and the sublingual gland. All flaps were monitored for complications including skin loss and ischemia. The functions of appearance, swallowing, and speech were assessed 6 months after operation with the University of Washington Quality of Life Questionnaire. RESULTS: All flaps presented with satisfactory results except for one, which demonstrated superficial tip necrosis that settled after conservative treatment. The follow-up period ranged from 6 to 12 months, and 1 patient died as a result of pulmonary metastasis, and 3 patients underwent second surgery because of local tumor recurrence (2patients) and cervical recurrence (1 patient). Nineteen patients were assessed with the University of Washington Quality of Life Questionnaire, and the mean (SD) scores of appearance, swallowing, and speech were 57.89 (14.45), 83.68 (19.98), and 81.58 (23.16), respectively. CONCLUSIONS: This design of facial artery perforator flaps could provide an efficient and cost-effective method for reconstruction of small- to medium-sized intraoral defects with a low surgical morbidity and satisfactory levels of quality of life.

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.

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and nonsyndromic orofacial clefts susceptibility in a southern Chinese population.

Nonsyndromic orofacial clefts (NSOC) are one of the most common congenital anomalies in humans. Great efforts have been taken to unravel its genetic background. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism and two of its functional polymorphisms, MTHFR C677T and MTHFR A1298C, might be associated with NSOC susceptibility. The aim of the present study was to investigate their associations with risks of NSOC in a southern Chinese population. We found that MTHFR 677 TT and 677 CT/TT were associated with increased risk of cleft lip with or without cleft palate; meanwhile, MTHFR 1298 AC and 1298 AC/CC had protective effects against cleft lip with or without cleft palate. In further stratified analysis, we found that MTHFR 677 CT contributed to elevated risk of cleft lip only, as did MTHFR 677 CT/TT. On the contrary, MTHFR 1298 AC and 1298 AC/CC appeared to be protective against cleft lip with cleft palate. These results suggested that these two polymorphisms were involved in the development of NSOC in a southern Han Chinese population.