Xinchun Jian

Anthropometric measurement and analysis of the external nasal soft tissue in 119 young Han Chinese adults.

A random sample of 119 young, healthy Han Chinese adults (56 men and 63 women) between the age of 18 and 25 years (mean, 22.7 y) in PR China was obtained for this study. By the guidance of standard methods, based on Farkass anthropometric measurements in craniofacial region, 12 nasal soft tissue landmarks and 12 linear and 3 angular measurements were chosen. The linear measurements were taken directly, whereas the angular measurements were taken by photogrammetric method. Eight nasal proportion indices were calculated according to the linear measurements. The application of the independent-samples t-test showed sex dimorphism in most parameters of the nasal region. All the linear measurements were larger in men than in women, whereas all the angular measurements were smaller in men than in women. The significant differences in partial parameters between men and women have been proved. Ten of 12 linear measurements, 1 of 3 angular measurements, and 3 of 8 nasal proportion indices showed significant sexual dimorphism (P < 0.01). Compared with other racial/ethnic groups, the nasal anthropometric measurements and proportion indices of Han Chinese adults were different, to some extent. This study could provide credible and objective reference material for plastic and maxillofacial surgeons for the external nasal soft tissue evaluation and planning of the cosmetic nasal surgery. Besides, these results could be a useful guidance for preoperative and postoperative evaluations of secondary rhinoplasty in nasal deformity associated with cleft lip and palate.

Discovery of Novel Biomarkers in Oral Submucous Fibrosis by Microarray Analysis

Oral submucous fibrosis (OSF) is a high-risk precancerous condition of the oral cavity. Areca nut chewing is its key etiologic factor, but the full pathogenesis is still obscure. In this study, microarray analysis was used to characterize the mRNA changes of 14,500 genes in four OSF and four normal buccal mucosa samples to identify novel biomarkers of OSF. Five candidate genes with the most differential changes were chosen for validation. The correlation between clinicopathologic variables of 66 OSF patients and the expression of each gene was assessed by immunohistochemistry. The microarray analysis showed that 661 genes were up-regulated (fold value >2) and 129 genes were down-regulated (fold value <0.5) in OSF (q < 0.01). The top three up-regulated genes [Loricrin, Cartilage oligomeric matrix protein (COMP), Cys-X-Cys ligand 9 (CXCL9)] with the largest fold changes and the top two down-regulated genes [keratin 19 (KRT19), cytochrome P450 3A5 (CYP 3A5)] with the most significantly differential changes in OSF were chosen as candidate biomarkers. In immunohistochemical results, the expression of Loricrin and COMP showed statistically significant association with histologic grade of OSF (P = 0.03 and 0.006, respectively). COMP was found to be overexpressed frequently in patients with the habit of areca nut chewing for more than 4 years (P = 0.002). CYP 3A5 was revealed an inverse correlation with histologic grade (P = 0.04). This pilot study showed that five novel genes might play important roles in the pathogenesis of OSF and may be clinically useful for early detection of OSF. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2249–59)

Tripaddled anterolateral thigh flap for simultaneous reconstruction of bilateral buccal defects after buccal cancer ablation and severe oral submucous fibrosis release: a case report.

For buccal squamous cell carcinoma (SCC) patients accompanied with severe oral submucous fibrosis (OSF), it is a challenge to simultaneously reconstruct bilateral buccal defects created from cancer resection and contralateral OSF release to improve postoperative mouth opening. Herein, we present a case of reconstruction of bilateral buccal defects in a 46‐year‐old patient who had left buccal SCC accompanied with severe OSF. Extensive ablation involved the left full‐thickness cheek as well as part of mandible and a release of right OSF tissue were performed. A tripaddled anterolateral thigh (ALT) flap with three independent sets of perforators was harvested for reconstruction. The flap survived in its entirety. No donor or recipient site complication occurred. The preoperative inter‐incisor distance (IID) was 1 mm, while the postoperative IID was 23 mm. This is the first report on the use of one tripaddled ALT flap for reconstruction of bilateral buccal defects created from cancer ablation and severe contralateral OSF release.

Synergistic effects of betel quid chewing, tobacco use (in the form of cigarette smoking), and alcohol consumption on the risk of malignant transformation of oral submucous fibrosis (OSF): a case-control study in Hunan Province, China

OBJECTIVES Oral submucous fibrosis (OSF) is a potentially malignant disorder, wherein 7% to 13% of patients with OSF develop oral squamous cell carcinoma (OSCC) at clinically coincident sites established to have OSF. We aimed at investigating the lifestyle-related risk factors for malignant transformation of OSF. STUDY DESIGN A case-control study was conducted among 80 cases with OSF-associated OSCC and 80 controls with OSF but without clinically or histopathologically evident OSCC, recruited from January 2012 to October 2014 in the Xiangya Hospital, Hunan Province, Mainland China. RESULTS The odds ratios (OR) for OSCC were 13.3 (95% confidence interval [95% CI]: 3.1-56.4) and 45.1 (95% CI: 9.6-212.9) at the highest exposure of betel quid (BQ) chewing, by duration and frequency, respectively. Higher risks were also found to be associated with the consumption of cigarette (OR = 5.0, 95% CI: 1.7-14.8) and alcohol (OR = 3.1, 95% CI: 1.1-8.6). Adjusted ORs increased substantially among patients who consumed BQ and cigarette or alcohol simultaneously, which were 26.1 (95% CI: 4.0-172.6) and 55.-(95% CI: 1.8-1742.8) at the longest duration, and 160.3 (95% CI: 18.7-11371.2) and 58.1 (95% CI: 2.4-1434.9) at the highest dose, respectively. CONCLUSIONS The use of BQ, cigarette, and alcohol were identified as risk factors for malignant transformation of OSF in the Hunan province, Mainland China. Synergistic effects between BQ chewing and cigarette or alcohol consumption were revealed.

Multipaddled anterolateral thigh chimeric flap for reconstruction of complex defects in head and neck

The anterolateral thigh flap has been the workhouse flap for coverage of soft-tissue defects in head and neck for decades. However, the reconstruction of multiple and complex soft-tissue defects in head and neck with multipaddled anterolateral thigh chimeric flaps is still a challenge for reconstructive surgeries. Here, a clinical series of 12 cases is reported in which multipaddled anterolateral thigh chimeric flaps were used for complex soft-tissue defects with several separately anatomic locations in head and neck. Of the 12 cases, 7 patients presented with trismus were diagnosed as advanced buccal cancer with oral submucous fibrosis, 2 tongue cancer cases were found accompanied with multiple oral mucosa lesions or buccal cancer, and 3 were hypopharyngeal cancer with anterior neck skin invaded. All soft-tissue defects were reconstructed by multipaddled anterolateral thigh chimeric flaps, including 9 tripaddled anterolateral thigh flaps and 3 bipaddled flaps. The mean length of skin paddle was 19.2 (range: 14–23) cm and the mean width was 4.9 (range: 2.5–7) cm. All flaps survived and all donor sites were closed primarily. After a mean follow-up time of 9.1 months, there were no problems with the donor or recipient sites. This study supports that the multipaddled anterolateral thigh chimeric flap is a reliable and good alternative for complex and multiple soft-tissue defects of the head and neck.

Novel genetic biomarkers for susceptibility to oral submucous fibrosis: Cytochrome P450 3A

Oral submucous fibrosis (OSF) is a chronic and insidious oral mucosal disease, which always carries high risk of transition to oral cancer. Mainly based on genetic predisposition in pharmacokinetics for toxic substances of betel quid, there are obviously variable responses to betel quid among chewers. But the key genes resulting in interindividual variability in OSF development are still obscure. The cytochrome P450 3A (CYP 3A) gene family plays major roles in the oxidative metabolism of active endogenous and xenobiotic substrates, which is generally found polymorphic with variant alleles in different individuals and regarded as a major determinant of the interindividual variability in chemicals pharmacokinetics. Based on the specific property of CYP 3A, we consider this polymorphically expressed genotype could be a predictor of OSF susceptibility. Betel-quid chewers with lower level of CYP 3A expression might be more susceptible to toxicity of betel quid, resulting in higher risk of OSF lesion. Meanwhile, individuals at genetically high risk of OSF could be screened according to the genetic polymorphisms in some exclusive regions of the CYP 3A genes. By analyzing the polymorphisms of CYP 3A genes, we could differentiate interindividual variability for pharmacokinetics of betel-quid chewers, and then guide OSF therapy.

Multiple logistic regression analysis of risk factors for carcinogenesis of oral submucous fibrosis in mainland China

Oral submucous fibrosis (OSF), a chronic progressive disorder, is regarded as the premalignant lesion of oral squamous cell carcinoma (OSCC). Its distribution is associated with chewing betel quid (BQ). The objective of the present study was to investigate risk factors for the carcinogenesis of OSF in mainland China. A case-control study was performed in 42 patients with OSCC that originated from OSF and 40 OSF controls. Epidemiological data and information related to risk factors were collected using a short structured questionnaire. Odd ratios (OR) and 95% confidence intervals (CI) were derived from logistic regression analysis. In multivariate analysis, only age, duration of BQ chewing, duration of cigarette smoking, and OSF accompanied by oral leukoplakia or oral lichen planus were associated with significantly increased risk for the malignant transformation of OSF. These findings contribute to current knowledge on the prevention of carcinogenesis of OSF in mainland China.

miR-203 inhibits arecoline-induced epithelial‑mesenchymal transition by regulating secreted frizzled-related protein 4 and transmembrane-4 L six family member 1 in oral submucous fibrosis

Oral submucous fibrosis (OSF) is a potentially malignant disease predominantly found in Asian people. The areca nut has been implicated in this disease. Arecoline, one of the areca alkaloids, induces epithelial-mesenchymal transition (EMT)-related factors in primary human buccal mucosal fibroblasts. Yet, the mechanisms of the underlying arecoline-induced EMT in OSF remain unknown. In the present study, we aimed to investigate the role of microRNAs (miRNAs) in arecoline-induced EMT in HaCaT cells. We found that miR-203 was significantly downregulated in OSF tissues compared to that in normal buccal mucosa tissues, and that miR-203 negatively regulated secreted frizzled-related protein 4 (SFRP4) and positively regulated transmembrane-4 L six family member 1 (TM4SF1). We observed that upregulation of miR-203 significantly decreased the cell proliferation of HaCaT cells, and significantly upregulated the expression of cytokeratin 19 (CK19) and E-cadherin proteins, whereas it significantly downregulated the expression of N-cadherin and vimentin compared to these levels in the vehicle control cells. Thus, we provide evidence to illustrate that miR-203 plays a role in the pathogenesis of OSF, which may be a target for OSF management.

Insulin augments mechanical strain‑induced ERK activation and cyclooxygenase‑2 expression in MG63 cells through integrins

Insulin has been proposed to be a positive regulator of osteoblast proliferation and bone formation. In vivo mechanical loading is essential for maintaining skeletal integrity and bone mass. Since insulin and mechanical force activate similar signaling pathways in osteoblasts, it was hypothesized that insulin may affect mechanical stimulation in osteoblasts. The present study tested the hypothesis that insulin augments mechanical strain-induced signaling and early gene expression in MG63 cells via activation of the extracellular signal-regulated kinase (ERK) pathway and cyclooxygenase-2 (Cox-2) expression. Western blot analysis and quantitative polymerase chain reaction demonstrated respectively that insulin enhanced mechanical strain-induced ERK phosphorylation and Cox-2 expression levels in a dose-dependent manner. The effect of insulin on mechanical strain-induced Cox-2 expression was inhibited by blockade of the ERK pathway. In addition, echistatin, an inhibitor of integrin function, prevented the effects of insulin on mechanical strain-induced ERK phosphorylation and Cox-2 expression. The data obtained from this study suggested that insulin augments mechanical strain-induced Cox-2 expression levels via integrin-dependent activation of the ERK pathway in osteoblasts.

Cys-X-Cys ligand 9 might be an immunological factor in the pathogenesis of oral submucous fibrosis and its concomitant oral lichenoid lesion

ObjectivesOral submucous fibrosis (OSF) is a chronic oral precancerous disease primarily caused by betel quid chewing. Some OSF patients are concomitant with oral lichenoid lesion (OLL), a white-streak lesion with a higher risk for cancerization, in OSF mucosa. Immunological reaction has been considered as one of their common pathogenic mechanisms. Cys–X–Cys ligand 9 (CXCL9) is an important factor to recruit effector neutrophils and lymphocytes in immunological reactions. However, the expression levels of CXCL9 in OSF and OLL remain unclear.Materials and methodsWe investigated the expression levels of CXCL9 in 10 normal buccal mucosa (NBM) samples and 56 OSF concomitant with OLL patients, and evaluated the possible mechanism of CXCL9 on their pathogenesis.ResultsOur results showed NBM demonstrated negative CXCL9 expression. OSF stained positive CXCL9 mainly in the cytoplasm of inflammatory cells and endothelial cells throughout the superficial layer of connective tissue, while its concomitant OLL showed much stronger CXCL9 in all mononuclear cells of subepithelial inflammatory infiltration (p = 0.0006). There was an upregulated trend of CXCL9 expression from NBM to OSF to OLL. However, no significant association between CXCL9 expression and clinicopathologic parameters of patients was found.ConclusionsIn conclusion, CXCL9 was found for the first time to contribute to the immunological pathogenesis for both OSF and its concomitant OLL, indicating a continuously enhanced intensity of immunoreactivity in their pathogenic process.Clinical relevanceCXCL9 might be a useful tool to monitor the phase and disease severity of OSF and OLL, and a potential target for further clinical therapy for both lesions.