[Identification of rare variants in exons of NLRC4 gene in patients with type 1 diabetes and their impact on gene function].

Objective: To identify rare variants in exon and exon-intron boundary of containing NLR family CARD domain protein 4 (NLRC4) in type 1 diabetes (T1DM) patients, and to explore their effects on gene function. Methods: A total of 508 T1DM patients and 527 healthy controls in the Department of Metabolic Endocrinology, Second Xiangya Hospital of Central South University from August 2017 to September 2020 were selected. The case group included 264 males and 244 females, and the age [M (Q1, Q3)] was [27 (11, 43)] years. The control group included 290 males and 237 females, and their ageï¼»M（Q1，Q3）］was [47 (36, 60)] years old. Identification of rare variants in exons of NLRC4 gene in T1DM patients and healthy controls was performed and verified by next-generation sequencing and sanger sequencing. The NLRC4 gene wild-type and mutant plasmids were constructed and transfected into 293T cells. Western blot (WB) was used to detect the expression of NLRC4 protein and cleavage products of pro-cysteinyl aspartate specific proteinase(procaspase-1). Cycloheximide (CHX) was added to 293T cells transfected with wild-type or mutant NLRC4 plasmid to detect the degradation of NLRC4 protein. The localization of NLRC4 protein was detected by immunofluorescence, and the concentration of IL-1ß in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Results: The sequencing results showed that 4 patients and 2 healthy controls had a heterozygous variant c.208C>T in exon 3 of the NLRC4 gene. Two patient had a heterozygous variant c.1564T>C in exon 4, and 1 patients had c.1219G>C in exon 4. These three variants might be pathogenic variants in T1DM. In 293T cells transfected with NLRC4 wild-type and c.208C>T、c.1564T>Cc.1219G>C mutant plasmids, the expression level, degradation rate, localization of NLRC4 protein and the content of cleavage products of procaspase-1 did not change significantly. However, the concentration of IL-1ß secreted by 293T cells transfected with c.1219G>C and c.208C>T plasmid [M(Q1, Q3)] was 15.25 (12.98, 17.52) and 15.44 (13.81, 17.07) ng/L, respectively, which was lower than 18.70 (16.59, 20.81) ng/L of 293T cells transfected wild-type plasmid (P=0.020, 0.010). Conclusions: NLRC4 gene rare variants c.208C>T, c.1564T>C and c.1219G>C may not change the protein expression, degradation and localization, but c.208C>T and c.1219G>C may inhibit the secretion of IL-1ß. This result suggests that NLRC4 rare variants may have an impact on gene function.

[Study on the clinical significance of miR-100 expression in the invasion and metastasis of hepatocellular carcinoma].

Objective: To study the miR-100 expression levels in the tissues of hepatocellular carcinoma patients, and to further explore the correlation between miR-100 and the invasion and metastasis of hepatocellular carcinoma cells and its effect on patients' prognostic survival. Methods: Clinicopathological data of 70 cases that underwent hepatectomy from December 2013 to December 2016 in the Department of Hepatobiliary and Pancreatic Surgery of Henan Provincial People's Hospital were retrospectively analyzed. Real-time fluorescent quantitative PCR was used to detect the different miR-100 expression levels in cancerous and adjacent tissues. The expression of miR-100 with different clinicopathological features was compared, and the prognostic factors of patients with hepatocellular carcinoma were comprehensively analyzed. The correlation between miR-100 and patients' clinicopathological features was tested by χ(2). Kaplan-Meier method was used to draw the survival curve. Log-rank test was used to examine the survival rate difference in each subgroup. Cox regression model was used to analyze the multivariate prognosis. Results: miR-100 expression was down-regulated to a different degree in hepatocellular carcinoma tissues than the corresponding adjacent tissues. Among them, the down-regulated expression of miR-100 in hepatocellular carcinoma tissues accounted for 82.9% (58/70, P < 0.05) of all cases when compared to corresponding paracancerous tissues. miR-100 expression level was significantly correlated to high Edmondson's grade, high TNM stage and intrahepatic metastasis (P < 0.05). The overall survival time of miR-100 positive expression was significantly higher than that of miR-100 negative expression (Log-rank χ(2) = 8.257, P < 0.05). Univariate survival analysis results revealed that the miR-100 expression level, tumor size, TNM stage, Edmondson's grade, and presence or absence of venous tumor thrombosis had a poor prognosis (P < 0.05). Cox multivariate regression analysis showed that the tumor size, Edmondson's grade, and miR-100 expression level were independent factors affecting the prognostic survival in hepatocellular carcinoma patients. In addition, patients with low positive expression rate of miR-100, large tumors and high Edmondson's grade had a poor prognosis. Conclusion: The level of miR-100 expression in hepatocellular carcinoma cells is low, so it is closely related to the invasion and metastasis and affects the prognostic survival of hepatocellular carcinoma patients.

[125â seed brachytherapy for recurrent salivary gland carcinoma after external radiotherapy].

OBJECTIVE: To investigate the clinical application and efficacy of 125Ⅰ radioactive seeds implantation in the treatment of recurrent salivary gland carcinoma after external radiotherapy. METHODS: From July 2004 to July 2016, 43 cases of recurrent salivary gland carcinoma of the neck after external radiotherapy or surgery combined with external radiotherapy were treated. According to the conventional segmentation radiotherapy for head and neck cancer (once a day, 1.8-2.0 Gy each time, 5 days per week), the cumulative radiation dose of the patients in this group was calculated. In the study, 26 patients received 50-60 Gy, 7 patients received less than 50 Gy, 4 patients received 60-70 Gy, and 6 patients received more than 80 Gy (range: 80-120 Gy). The interval between the last external irradiation and local recurrence was 4-204 months, and the median interval was 48 months. Among them, 25 cases were treated with 125Ⅰ radioactive seeds implantation only and 18 cases were treated with 125Ⅰ radioactive seeds implantation after operation. The prescription dose was 100-140 Gy. The control rate, survival rate and disease-free survival rate were recorded to evaluate the side effects. RESULTS: The median follow-up time was 27 months (ranging from 2.5 to 149.0 months). Among them, the median follow-up time of adenoid cystic carcinoma patients was 31 months (range: 2.5-112.0 months), and the median follow-up time of mucoepidermoid carcinoma patients was 18 months (range: 5-149 months). The local control rates for 1, 3 and 5 years were 66.5%, 48.8% and 42.7%, respectively. The 1-, 3- and 5- year survival rates were 88.0%, 56.7% and 45.8%, respectively. The disease-free survival rates of 1, 3 and 5 years were 58.3%, 45.4% and 38.1%, respectively. There was no statistically significant difference in local control rate, survival rate, and disease-free survival between the radioactive seeds implantation group and the radioactive seeds implantation group after surgical resection. There were 2 cases of acute radiation reaction Ⅰ/Ⅱ and 3 cases of reaction Ⅲ or above. In the late stage of radiotherapy, there were 8 cases with Ⅰ/Ⅱ grade reaction and 3 cases with Ⅲ grade or above reaction. The incidence of radiation reactions of Grade Ⅲ and above was 7%. CONCLUSION: 125Ⅰ radioactive seeds implantation provides an alternative method for the treatment of recurrent salivary gland carcinoma after external radiotherapy. The local control rate and survival rate are improved on the premise of low incidence of side effects.

[Application and efficacy of the adjustment on left ventricular electrical delay and the distance between right and left ventricular pacing polar in optimizing the left ventricular pacing polar].

Objective: To investigate the application and efficacy of left ventricular (LV) electrical delay (LVED) and the distance of right ventricular(RV) pacing polar to LV(DRLV) in optimizing LV pacing polar. Methods: Heart failure (HF) patients who implanted cardiac resynchronization therapy (CRT) device with a LV quadripolar lead from January 2014 to January 2018 at General Hospital of Northern Theater Command were enrolled in the study. Measurements of LVED and DRLV of each polar of the lead were performed in patients with HF who underwent CRT with LV quadripolar lead. The principle in turn for polar selecting used for clinical LV pacing was the pacing polar: (1)without phrenic nerve stimulation(PNS); (2)with appropriate capture threshold; (3)not located in apical; (4)with maximal LVED; (5)with maximal DRLV. The LV pacing polar was selected for CRT according to the procedure. The distribution of target veins implanted with LV quadripolar lead were calculated. The percentage of biventricular pacing at 6-month follow-up was recorded. The following indexes were compared before and 6-month after surgery, including QRS duration, LV end-systolic volume(LVESV), LV ejection fraction(LVEF), LV end-diastolic dimension(LVEDD), 6 minute walking distance(6MWD), New York Heart Association(NYHA) class. The efficacy and echocardiographic efficacy of CRT was evaluated. Results: There were twenty-nine HF patients enrolled. The mean age of enrolled patients was(61.7±7.6)years old, nineteen (66%)of them were male. There were seventeen(59%) patients diagnosed as dilated cardiomyopathy and twelve(41%) patients as ischemic cardiomyopathy. All patients were successfully implanted with LV quadripolar lead into target veins, and all four pacing sites were also in target veins. Target veins were located in lateral veins in 15 patients (52%), anterior veins in 2 patients (7%), posterior veins in 11 patients (38%), and lateral branches of great cardiac veins in 1 patient (3%). After 6-month of follow-up, the percentage of biventricular pacing was greater than 95%.There were nineteen(66%) patients optimized LV pacing polar by the largest LVED and four (14%) patients by the DRLV. Of the 29 patients, 5(17%) patients used D1 as the pacing polar, 5(17%) patients used M2 as the pacing polar, 7(24%) patients used M3 as the pacing polar, and 12(41%) patients used P4 as the pacing polar. The pacing polars (D1, M2) of traditional bipolar lead were used in 10(34%) patients, and the LV quadripolar lead specific pacing polars (M3, P4) were used in 19(66%) patients.Compared to a LV quadripolar lead, the LV pacing polar (M3, P4) selected in 19(66%) patients were not achievable with the traditional LV bipolar lead (D1, M2). Preoperative QRS duration, LVESV, LVEF, LVEDD, 6MWD and NYHA class were (171±24)ms, (231±79)ml, (28±5)%, (74±11)mm, (294±103)m, (3.2±1.0)class and the postoperative 6-month were (130±12)ms, (158±73)ml, (36±10)%, (66±12)mm, (371±86)m, (1.9±0.5)class. These indexes were significantly improved after 6 months operation(P<0.001). 97% and 83% patients were responders of CRT as assessed by 6-month efficacy and echocardiographic efficacy. Conclusion: The maximal LVED and DRLV can be used to select LV pacing polar with a high rate of CRT response rate.

An in silico pipeline for subject-specific hemodynamics analysis in liver surgery planning.

The progresses in fast simulations of the hepatic flow in subject-specific vascular tree have created new toolkits for pre-surgical planning. The aim of this short communication is to introduce a computational pipeline that integrates several recently developed in silico liver models and algorithms. Firstly, a semi-automatic segmentation pipeline is used to digitise hepatic vessels. Then, a constructive constraint optimisation (CCO) algorithm is used to extend the digitised vascular tree, and also to compute the blood pressure and flow velocity in the tree. Couinaud segments are simulated from the diffusion zones of the portal venous tree. The constructed surgical planning model is then deployed cross-platform for use in various scenarios.

Cadherin 6 is activated by Epstein-Barr virus LMP1 to mediate EMT and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in LMP1-positive NPC tissues, and was identified as a target of the epithelium-specific miR-203. LMP1-activated NF-κB transcriptionally repressed the miR-203 expression by binding to the promoter region of miR-203 gene. CDH6 activation in turn induced EMT and promoted metastasis in NPC. CDH6 depletion, NF-κB inhibitor and miR-203 overexpression were able to impair the EMT effects. The miR-203 downregulation in NPC tissues was strongly associated with metastasis clinically. The CDH6 activator, Runt-related transcription factor 2 (RUNX2), was also activated by EBV in the event. For both CDH6 and RUNX2 are components at TGF-ß downstream, CDH6 became a node protein for the interplay of multiple signalings including NF-κB and TGF-ß. Therefore, the switch-on of miR-203 was important for nasopharyngeal epithelial cells to maintain normal phenotype. This study demonstrates that EBV has evolved sophisticated strategies by driving epithelial cells to obtain malignant features, particularly in NPC metastasis, providing novel biomarkers for the therapy and prognosis of EBV-associated NPC.

[Clinical efficacy of enhanced recovery after surgery in atrial caval shunting for type â ¡ Budd-Chiari syndrome].

Objective: To investigate the clinical efficacy of enhanced recovery after surgery(ERAS) in atrial caval shunting (ACS) for type Ⅱ Budd-Chiari syndrome(BCS). Methods: The clinical data of patients underwent ACS for type Ⅱ BCS in the Henan Province People's Hospital from January 2014 to June 2016 were prospectively analyzed.Randomized and single-blind, controlled study was performed among the patients, and all of them underwent ACS and were divided into control group (patients underwent traditional perioperative management) and ERAS group (patients underwent ERAS perioperative management) based on a random number table.Operational and postoperative data, levels of inflammatory cytokines, stress state evaluation and postoperative complications were observed.The comparison between the two groups was evaluated with an independent sample t test.The trend analyses for variables were done using repeated measures ANOVA.The count data were analyzed using the chi-square test or Fisher exact. Results: Eighty-two patients were screened for eligibility, and allocated into the control group (40 patients) and the ERAS group (42 patients). All patients underwent ACS successfully with no death.Comparison of intraoperative status: operation time, volume of intraoperative blood and number of patients receiving blood transfusion were (211.0±12.9) minutes vs. (207.7±10.7) minutes, (167.5±28.3) ml vs. (165.0±28.4) ml and 3 cases vs. 1 case between the control group and the ERAS group, respectively, showing no difference between the two groups (t=0.90, 0.29, χ2=0.32, all P>0.05). Comparison of postoperative status: time of gastric tube removal, time of catheter removal, time of chest tube, time to flatus, time of food intake, duration of postoperative infusion, duration of postoperative hospital stay and numeric rating scale were (3.7±0.5)days vs. (0.0±0.0)days, (2.3±0.7)days vs. (1.4±0.5)days, (3.7±0.7)days vs. (2.3±0.5)days, (75.2±3.8)hours vs. (46.6±4.2)hours, (75.7±4.7)hours vs. (21.4±2.1)hours, (10.0±1.0)days vs. (5.8±0.9)days, (11.4±1.0)days vs. (7.8±0.6)days, 2.9±0.4 vs. 1.9±0.6 between the control group and the ERAS group, respectively, with statistically differences (t=35.03, 4.36, 8.10, 22.89, 47.78, 14.75, 14.22, 6.13, all P<0.05). Stress state evaluation: the levels of IR were (2.7±0.1) vs.(2.7±0.1), (8.8±0.7) vs. (5.2±0.3), (11.0±0.5) vs. (7.3±0.5), (4.9±0.2) vs. (3.9±0.1), and the levels of C-reaction protein were (14.6±1.3)mg/L vs.(14.6±1.1) mg/L, (101.2±13.6) mg/L vs. (89.5±6.9) mg/L, (62.7±8.6) mg/L vs. (56.4±8.4) mg/L, (46.4±6.7) mg/L vs. (40.0±5.6) mg/L from pre-operation to postoperative day 1, 3 and 5 between the control group and the ERAS group, respectively, with statistically significant differences in changing trends(F=136.61, 4.97, both P<0.05). Comparisons of levels of inflammatory cytokines: the levels of IL-6 were (43.1±2.7) ng/L vs. (43.6±3.6) ng/L, (135.1±6.4) ng/L vs. (117.4±5.7) ng/L, (145.4±6.7) ng/L vs. (128.5±5.5) ng/L, (93.3±3.7) ng/L vs. (88.0±3.9) ng/L, and the levels of TNF-α were (10.4±0.3)mmol/L vs. (10.4±0.3) mmol/L, (14.4±0.4) mmol/L vs. (12.6±0.4) mmol/L, (15.6±0.4) mmol/L vs. (13.8±0.4) mmol/L, (12.3±0.7) mmol/L vs. (11.4±0.6) mmol/L from pre-operation to postoperative day 1, 3 and 5 between the control group and the ERAS group, respectively, with statistically significant differences in changing trends (F=15.15, 21.45, both P<0.05). Comparison of postoperative complications: incidence of complications was 30.0%(12/40) in the control group and 11.9%(5/42) in the ERAS group, and the numbers of patients with nausea and vomiting, respiratory complications and cardiovascular complications were 4, 3, 5 cases in the control group and 3, 1, 1 case in the ERAS group, respectively, showing statistically differences in the incidence of complications(χ2=4.08, P<0.05). All the 82 patients were followed up for 2 to 22 months (median time, 12 months), no patients received reoperation or re-admitted to the hospital duo to complications. Conclusion: ERAS management in the perioperative period of ACS for BCS is beneficial to postoperative recovery of patients, and can relieve postoperative stress state and inflammatory response, reduce the duration of hospital stay, and incidence of postoperative complications.

Influence of temporomandibular joint disc displacement on mandibular advancement in patients without pre-treatment condylar resorption.

The purpose of this study was to clarify the correlation between pre-treatment anterior disc displacement and mandibular stability after orthognathic and orthodontic treatment among patients with a skeletal class II malocclusion and without pre-treatment condylar resorption. Thirty-seven patients were included (7 male, 30 female). The mean length of follow-up was 6.76±3.06 years. Patients with condylar resorption before treatment were excluded. Magnetic resonance images and lateral cephalometric radiographs were taken before treatment (T0), after treatment (T1), and at follow-up (T2). Patients were classified according to the degree of disc displacement: -10-10° 'normal', 11-50° 'slight to mild', ≥51° 'moderate to severe'. Results showed the condyle moved posterosuperiorly after treatment, and then moved anteriorly to a more concentric location during the long follow-up period. Condylar movement was found not to correlate with disc displacement. The degree of disc displacement before treatment did not correlate with the post-surgical mandibular positional change in either the sagittal or vertical direction. To conclude, the mandibular bilateral sagittal split ramus osteotomy was stable in the long-term after orthognathic and orthodontic treatment. In the absence of pre-treatment condylar resorption, the degree of initial anterior disc displacement did not have a significant influence on the stability of mandibular advancement.

[Establishment and application of a digital workflow in the treatment of condylar osteochondroma and secondary dentofacial deformities using image-guided endoscopic navigation combined with orthognathic surgery].

Objective: To establish a digital workflow in the treatment of mandibular condylar osteochondroma with secondary dentofacial deformities using navigation and endoscope combined with orthognathic surgery. Methods: Thirty-six patients with unilateral condylar osteochondroma were analyzed retrospectively. Preoperative planning and simulation were carried out on the digital three-dimansional (3D) model in all patients. With the aid of image-guided endoscopic navigation, osteochondroma resection and condylectomy were accurately performed. Secondary dentofacial deformities were simultaneously corrected using orthognathic surgery. All patients were followed up regularly and received postoperative CT scans. The preoperative simulated model and the postoperative actual model were matched using ProPlan CMF 2.0 software. Four corresponding points were marked in the virtual and actual ostectomy plane, respectively. The intersections of mandibular sigmoid notch and posterior ramusrim with condylectomy plane were marked as the anterior point and the posterior point, respectively. The perpendicular bisector of the line from the anterior point to the posterior point was intersected with the lateral and medial margin of condylectomy plane to form the lateral point and the medial point, respectively. The straight-line distances between the corresponding points in the virtual and actual ostectomy plane were respectively measured to analyze the ostectomy discrepancy. Results: All of 36 patients obtained satisfactory clinical effects. Facial symmetry and morphology were greatly improved. Postoperative CT showed that condylar tumors were completely removed. The preoperative simulated model and the postoperative actual model were matched. The average discrepancy between the planned and actual surgical resection was minimal on the anterior points ([0.24 ± 0.17] mm) and the mean error was maximal on the posterior points ([3.86±1.03] mm). The patients showed no signs of tumor recurrence in the 6 to 12 months of follow-up. Conclusions: Endoscope-assisted and navigation-guided tumor resection and condylectomy combined with simultaneous orthognathic surgery has satisfactory clinical effects in the treatment of condylar osteochondroma and secondary dentofacial deformities. The digital management workflow reported in this paper provides us a valuable option for this potentially complicated procedure.

The surgery-first approach in orthognathic surgery: a retrospective study of 50 cases.

The surgery-first approach (SFA), without presurgical orthodontic treatment, has become favoured in the treatment of dentomaxillofacial deformities. This approach has been applied in our institution since 2012. The purpose of this study was to report our experience with the SFA for skeletal malocclusion. Fifty patients with skeletal malocclusions were enrolled in this study (11 bimaxillary protrusion, 27 skeletal class III malocclusion, and 12 facial asymmetry). After orthognathic-orthodontic consultation, suitability for SFA was determined and a treatment plan drawn up. Patients then underwent orthognathic surgery, which included Le Fort I maxillary osteotomy, bilateral sagittal split ramus osteotomy, subapical osteotomy, and genioplasty. Postoperative orthodontic treatment was started after a healing period of 2 weeks. The mean postoperative orthodontic treatment duration was 14.9 months, which is shorter than that of traditional joint orthognathic-orthodontic treatment. In the bimaxillary protrusion group, this was about 19 months, which was longer than for the other groups. After joint orthognathic-orthodontic treatment, a good facial profile and ideal occlusion were achieved. With the advantages of earlier improvements in patient facial aesthetics and dental function, the reduction in difficulty and treatment duration of orthodontic management, and increasing patient acceptance, SFA is regarded as an ideal and valuable alternative for this potentially complicated procedure.

Computer-assisted surgical planning and intraoperative navigation in the treatment of condylar osteochondroma.

Mandibular condylar osteochondroma (OC) results in asymmetric prognathism with facial morphology and functional disturbances. The aim of this study was to explore the feasibility of computer-assisted surgical planning combined with intraoperative navigation in the treatment of condylar OC. Five patients with mandibular condylar OC were enrolled in this study. Surgical planning and simulation was performed based on a computed tomography reconstruction model using SurgiCase software. Under the guidance of navigation, a condylar OC resection and conservative condylectomy was carried out via intraoral approach. Simultaneous orthognathic surgery was used to correct the facial asymmetry and malocclusion. All patients healed uneventfully. No facial nerve injury or salivary fistula occurred. Facial symmetry and morphology were greatly improved and stable occlusion was obtained in all cases. Good matching between preoperative planning and postoperative results was achieved. Patients showed no signs of recurrence or temporomandibular joint ankylosis during follow-up of 12-30 months. Computer-assisted surgical planning and intraoperative navigation is a valuable option in the treatment of mandibular condylar OC.

Endoscope-assisted conservative condylectomy in the treatment of condylar osteochondroma through an intraoral approach.

Mandibular condylar osteochondroma (OC) can result in morphological and functional disturbances, including facial asymmetry and temporomandibular joint (TMJ) dysfunction. The aim of this study was to explore the feasibility of endoscope-assisted tumour resection and conservative condylectomy via an intraoral approach. Seven patients with condylar OC were enrolled in this study. Endoscope-assisted tumour resection and conservative condylectomy were achieved intraorally, and no conventional extraoral incision was needed. Direct vision of the magnified and illuminated operative field was realized with the assistance of an endoscope. No facial nerve injury or salivary fistula occurred in any patient. Stable occlusion was realized through postoperative orthodontic treatment. The patients showed no signs of tumour recurrence or TMJ ankylosis during follow-up (range 18-43 months). Endoscope-assisted condylar OC resection and conservative condylectomy via intraoral approach offers great advantages with no significant complications compared with conventional extraoral incisions. The endoscope provides us with a valuable treatment option for this potentially complicated procedure.

Navigation-guided gap arthroplasty in the treatment of temporomandibular joint ankylosis.

Gap arthroplasty, used in the treatment of temporomandibular joint (TMJ) ankylosis, is challenging, requiring resecting of massive abnormal bone formation at the skull base with complex and distorted anatomy. This study evaluated the application of image-guided navigation to gap arthroplasty. Four gap arthroplasties were performed on patients with unilateral TMJ ankylosis under computer-assisted navigation guidance. After preoperative planning and 3-dimensional simulation, the normal anatomic structures of the TMJ were created by superimposing and comparing the unaffected and affected sides. The amount and range of ankylotic bone to be resected was determined and displayed. Registration achieved an accurate match between the intra-operative anatomy and the CT virtual images. Anatomic structures and the position of surgical instruments were shown real time on the screen. In all cases the accuracy of the system measured by the computer did not exceed 1mm. No complications occurred and the mean minimal thickness of the skull base between middle cranial fossa and reconstructed glenoid fossa was 1.97 mm. Using image-guided navigation resulted in safe surgical excision of the bony ankylosis from the skull base. Navigation-guided resection of the ankylotic bone in the TMJ gap arthroplasty was a valuable and safe technique in this potentially complicated procedure.

Alterations of p16INK4a tumour suppressor gene in mucoepidermoid carcinoma of the salivary glands.

Mucoepidermoid carcinoma (MEC) is common in the salivary glands, but alterations of the p16(INK4a) tumour suppressor gene are largely unknown. The aim of this study was to analyse p16(INK4a) gene alterations in MEC, and evaluate their significance for carcinogenesis. Thirty-eight salivary glands with MEC and six normal salivary glands were studied for p16(INK4a) alterations. In the MEC-affected group, there were 23.7% (9/38) and 13.2% (5/38) cases of homozygous deletion, and 5.3% (2/38) and 2.6% (1/38) cases of point mutation in p16(INK4a) exon 1 and exon 2, respectively. Hypermethylation of the p16(INK4a) gene promoter was found in 13 cases (13/38, 34.2%). Alterations of the p16(INK4a) gene were not found in the normal salivary glands. These findings suggest that the main mechanisms of inactivation of the p16(INK4a) gene in MEC of the salivary glands are promoter hypermethylation and homozygous deletion.

Multiplexing of optical fiber gas sensors with a frequency-modulated continuous-wave technique.

We report on the use of a frequency-modulated continuous-wave technique for multiplexing optical fiber gas sensors. The sensor network is of a ladder topology and is interrogated by a tunable laser. The system performance in terms of detection sensitivity and cross talk between sensors was investigated and found to be limited by coherent mixing between signals from different channels. The system performance can be improved significantly by use of appropriate wavelength modulation-scanning coupled with low-pass filtering. Computer simulation shows that an array of 37 acetylene sensors with a detection accuracy of 2000 parts in 10(6) for each sensor may be realized. A two-sensor acetylene detection system was experimentally demonstrated that had a detection sensitivity of 165 parts in 10(6) for 2.5-cm gas cells (or a minimum detectable absorbance of 2.1 x 10(-4)) and a cross talk of -25 dB.