Fusion of Audio and Vibration Signals for Bearing Fault Diagnosis Based on a Quadratic Convolution Neural Network.

In this paper, a quadratic convolution neural network (QCNN) using both audio and vibration signals is utilized for bearing fault diagnosis. Specifically, to make use of multi-modal information for bearing fault diagnosis, the audio and vibration signals are first fused together using a 1 × 1 convolution. Then, a quadratic convolution neural network is applied for the fusion feature extraction. Finally, a decision module is designed for fault classification. The proposed method utilizes the complementary information of audio and vibration signals, and is insensitive to noise. The experimental results show that the accuracy of the proposed method can achieve high accuracies for both single and multiple bearing fault diagnosis in the noisy situations. Moreover, the combination of two-modal data helps improve the performance under all conditions.

A prevalence survey of cone-beam computed tomography use among endodontic practitioners / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical application of cone-beam computed tomography (CBCT) among endodontic practitioners, and to analyze the indications and reasonability of CBCT in the diagnosis and treatment of pulpal and periapical diseases.@*METHODS@#The clinical data were collected from patients who visited the Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology and underwent CBCT examination from January to December, 2021. The data with their complete clinical information (including clinical records, radiology request forms/reports, two-dimensional and three-dimensional imaging data) were included. Those who underwent CBCT examination for orthodontic or prosthodontics were excluded. The experience and training background of the endodontic specialists, the number of patients treated in the whole year, the objective and region of interest (ROI) of CBCT examination, technical parameters, such as machine type, field of view (FoV) and radiographic reports were collected and analyzed to evaluate the impact on diagnosis. Wilcoxon and Mann-Whitney tests were used to compare the distribution of CBCT ROI. Chi-squared test and pairwise comparison were used to compare the application of CBCT by endodontic specialists with different clinical experience (senior, middle and junior).@*RESULTS@#In 2021, a total of 3 308 CBCT scans were prescribed by 61 endodontic specialists who treated 34 952 patients throughout the year. 3 218 patients (male ∶female about 1 ∶2) amounting for 10% of the patients treated in the whole year who received CBCT scans with an median age of 35 years (28, 49). Around 98% CBCT examinations were performed after clinical examination and two-dimensional periapical radiographs were taken. The FoV of CBCT scanning less than 10 cm×10 cm accounted for 96% of the total number of the images. Among the 3 308 CBCT scans, 83% of the ROI were in posterior teeth, with a higher number of anterior teeth (Z=-2.278, P < 0.05). Maxillary and mandibular first molars accounted for 35% of the examined teeth. The objectives of CBCT scanning included three aspects: clarifying clinical diagnosis, guiding surgical and non-surgical endodontic treatment (including management of endodontic complications), and outcome assessment, accounting for 1 111 (34%), 1 745 (54%), 311 (10%), respectively. and the others 2%. In the diagnosis process, CBCT was mainly used for the diagnosis of chronic periapical periodontitis, root fracture, root resorption and dental trauma. In the study, 353 CBCT were used in the diagnosis of root fracture, with a positive diagnosis rate of 35% (125/353). 846 CBCT used to reveal the anatomy of the root canal system, of which 297 cases were used to find missed/extra canals after treatment failure, and 58% (171/297) were used to confirm the missed/extra canals. In the management of complications or errors, CBCT was mainly used to assist the diagnosis of perforation and to locate the separated instruments. In the study, 311 CBCT scans were used for outcome assessment, including 240 cases related to non-surgical treatment and 71 cases related to surgical endodontic treatment for follow-up or presence of clinical symptoms, and persistent lesions on 2D films. Among the 61 endodontic specialists who used CBCT, 23 (45%) were with senior experience, 15 (30%) with middle experience, and 23 (25%) with junior experience. The proportion of senior or junior experience prescribing CBCT examination was 10%, higher than that of middle experience (8%, χ12=39.4, χ22=29.1, P < 0.001). The application rate of chief endodontists was 18%, which was higher than that of associate chief endodontists (9%, χ12=139.4, P < 0.001). 31% (1 109/3 308) cases of diagnosis or treatment plans were changed after CBCT was taken.@*CONCLUSION@#Use of CBCT in endodontic practice could provide more clinical information, which is helpful for diagnosis, accurate treatment and prognosis evaluation.

Cone-beam computed tomography digital for measuring the inclination angle to the long axis of healthy maxillary anterior teeth and morphologically characterizing their labial bone plates / 华西口腔医学杂志

OBJECTIVE@#We aim to determine the thickness of the labial plate, the distance between the cement-enamel junction (CEJ) and alveolar crest, and the inclination angle of the long axis of healthy maxillary anterior teeth by using cone- beam computed tomography (CBCT).@*METHODS@#A total of 345 CBCT volumes obtained by Newtom VGI® CBCT were analyzed by using the NNT software. The digital measurements of the labial bone plate thickness at level 4 mm below the CEJ, the midpoint of tooth root and the radiological tooth apex, the distance between the CEJ and alveolar crest, and the angle between the long axis of the teeth and the long axis of alveolar process were obtained from the mid-sagittal planes of maxillary incisors and canines. Plate thickness 4 mm below the CEJ was measured, and values below ≥1 mm were recorded.@*RESULTS@#In the central incisor, 1) the angle between the long axis of the teeth and alveolar bone was 15.2°±6.2°, the distance between the CEJ and alveolar crest was (1.5±1.0) mm, labial bone plate thick-ness at 4 mm below the CEJ was (0.8±0.4) mm, the midpoint of tooth root was (0.6±0.4) mm, and the radiological tooth apex was (1.3±0.7) mm; in the lateral incisor, 16.2°±8.8°, (1.6±1.0) mm, (0.7±0.5) mm, (0.4±0.6) mm, and (1.1±0.7) mm, respectively; and in the canine, 19.0°±6.2°, (1.8±1.0) mm, (0.9±0.6) mm, (0.4±0.6) mm, and (1.2±0.7) mm, respectively. 2) The frequencies of plate thickness ≥1 mm were 28.3%, 25.8%, and 42.7% in the central incisor, lateral incisor, and canine, respectively. 3) The distance between the CEJ and alveolar crest was positively correlated with age. The correlation coefficients was 0.42 (P<0.01) in the central incisor, 0.50 (P<0.01) in the lateral incisor, and 0.62 (P<0.01) in the canine.@*CONCLUSIONS@#The thickness of labial bone plate is thin, the distance from CEJ to alveolar crest increases with age, and the long axis of the teeth is more inclined than the long axis of alveolar process. Knowledge of these special morphological characteristics can improve the safety and result for many dental procedures.

Effects of different methods on drying root canal by near-field microwave detection system / 北京大学学报(医学版)

OBJECTIVE@#To set up near-field microwave detection system, to evaluate the accuracy of measuring water and to compare the effects of different methods on drying root canal.@*METHODS@#Known and quantitative distilled water in Eppendorf tube and root canal was detected by near-field microwave detection system which was set up first. The microwave reflection coefficient was recorded so as to evaluate the accuracy of the measuring water. 12 single-rooted mandibular premolar teeth with apical matureness and a curvature less than 10° were decoronated, leaving roots 14 mm in length. After instrumentation to F3, the root canals were air-dried and injected with 10 μL distilled water each. Then all the root canals were assigned to 4 groups (n=12) according to different methods on root canal drying. Near-field microwave detection system was used to detect the change of water after air-drying and root canal drying so as to evaluate the effects of different root canal drying methods: (1) negative control group, the canals were injected with 10 μL distilled water and no root canal drying method was performed; (2) paper points drying experimental group, four #60 paper points were used to blot-dry the middle and upper part of the canal, followed by #40 paper points blot-drying the apical area. The above step was repeated with the tip of paper point that appeared with no water under microscope as finished; (3) 95% (volume fraction) ethanol drying experimental group, after the distilled water was removed with paper points (similar to paper points experimental group), 10 μL 95% ethanol was injected into the canal and was left in place for 10 s, then paper points were used to dry the canal; (4) 70% (volume fraction) isopropyl alcohol drying experimental group, after the distilled water was removed with paper points (similar to paper points experimental group), 10 μL 70% isopropyl alcohol was injected into the canal and was left in place for 10 s, then paper points were used to dry the canal. The linear correlation analysis was used to test the accuracy of the measuring water by near-field microwave detection method and physical measurement. The Pearson correlation coefficient was calculated based on the data. The effects of different methods on drying root canal were analyzed by Chi square test.@*RESULTS@#The R2 for the microwave reflection coefficient and the physical measurement of the water in Eppendorf tube and root canal were 0.991 and 0.970. The microwave reflection coefficient in all the experimental groups showed significant difference (P<0.05). After drying with paper points, the residual water was the most, and the microwave reflection coefficient was the highest: 0.023. While after 70% isopropyl alcohol drying root canal, the residual water was the least with the microwave reflection coefficient 0.006, showing that the effect of drying was the best.@*CONCLUSION@#Near-field microwave detection system could detect the change of water in root canal. The effect of root canal drying by 70% isopropyl alcohol was superior to 95% ethanol and paper points.

Relationship between periodontitis and osteoporosis in postmenopausal women / 北京大学学报(医学版)

OBJECTIVE@#To explore the relationships of periodontal parameters, cortical width on mental foramen and osteoporotic condition in postmenopausal women.@*METHODS@#Ninetyeight postmenopausal women between 50 to 65 years old were recruited. General conditions, such as age, menopausal age, duration of menopause, and body mass index (BMI) were recorded. Periodontal parameters were examined, including oral hygiene index simplified (OHI-S), probing depth (PD), clinical attachment loss (CAL), gingival recession (GR) and bleeding on probing (BOP). Panoramic radiograph was taken and the cortical width (CW) of mental foramen was measured on images. The examiner was celebrated. Bone mass density (BMD) of left hip and lumbar spine was assessed using standardized dual energy X-ray absorptiometry. According to World Health Organization, based on the T-score of BMD (difference of the measured BMD and the mean value of young white women in terms of standard deviations), the subjects were divided into osteoporotic group (T-score<-2.5) and non-osteoporotic group (T-score≥-2.5). These parameters were compared between the groups.@*RESULTS@#The number of osteoporotic group was 47 (47.96%). Ages and duration of menopause were significantly different between the groups. Osteoporotic group presented older ages [(59.64±4.58) years vs. (56.94 ± 4.26) years, P<0.05], and longer duration of menopause [(10.17± 5.37) years vs. (6.02 ±4.48) years, P<0.05]. There was no significant difference in menopausal age and BMI between the groups. BOP% was statistically significantly higher in osteoporotic group (29.43±21.12) than in non-osteoporotic group (21.43±17.09), with a P-value of 0.046. The other periodontal parameters, including OHI-S, PD, CAL, and GR were not statistically significantly different in the groups. The CWs were statistically significantly lower in osteoporotic group compared with non-osteoporotic group, with a P-value of 0.001. The mean values of CWs were (3.61±1.04) mm (osteoporotic group) and (4.25±0.77) mm (non-osteoporotic group), respectively.@*CONCLUSION@#The study demonstrated absence of a significant association between periodontal parameters and BMD. However, the CWs were found to be related with the BMD, which may be used to detect BMD abnormal in maxillofacial imaging. The dentists should pay attention not only to the oral health, but also to the general bone mass density, which may be detected on panoramic images.

Construction of swept source optical coherence tomography imaging system for root canal endoscopy and application in diagnosis of root fractures / 北京大学学报(医学版)

OBJECTIVE@#To construct swept source optical coherence tomography (SS-OCT) imaging system for root canal endoscopy, and to evaluate the accuracy of diagnosing artificial root fractures.@*METHODS@#An ultra-high-speed (40 kHz) swept laser source was developed based on the piezoelectric tuning filter and the Fourier domain mode locking (FDML) swept laser technology (patent number: 200620135940.2). Ultra-miniature gradient index lens technology (patent number: 201320241218.7) was used to create a thin endoscopic probe with a diameter of 0.86 mm for real-time image transmission. The SS-OCT light source had a wavelength of 1 310 nm and a bandwidth of 100 nm. The axial and transverse image resolutions were 15 μm and 25 μm, respectively. Artificial fractures were created on human mandibular premolars with single root and the premolar roots were prepared to 41 horizontal sections (1 mm thick). 27 root sections with fractures (width: 52-284 μm) and 14 the sections without fractures were observed under an optical stereomicroscope with a cold light source as the gold standard. The horizontal root sections were scanned by self-developed SS-OCT imaging system for root canal endoscopy with a central wavelength of 1 310 nm and bandwidth of 100 nm. The data were reconstructed with 30 μm thick slices at an interval of 30 μm. Two observers, a radiologist and an endodontist, were trained and independently evaluated all the reconstructed images blindly. The diagnostic performance of SS-OCT imaging system was calculated, and statistical analysis was performed.@*RESULTS@#SS-OCT root canal endoscopic imaging system composed of high-speed swept laser source, fiber coupler, endoscopic probe, reference arm and differential detector. Root sections could be scanned by SS-OCT and imaged in realtime at a depth of 1 to 2 mm. The kappa value for interobserver agreement was 0.792, and the intraobserver agreement was 1.000 and 0.709 for two observers respectively. All of 27 fractured root sections and 12 of 14 root sections without fractures were accurately diagnosed while 2 unfractured root sections were misdiagnosed. The sensitivity was 1.000 and the specificity was 0.857 for diagnosis of artificial root fractures by SS-OCT. The positive predictive value (PPV), negative predictive value (NPV) and the overall accuracy rate were 0.931, 1.000 and 0.951 respectively.@*CONCLUSION@#The swept source optical coherence tomography imaging system for root canal endoscopy is a promising imaging method for observing root fractures．.

Cordyceps sinensis Promotes the Growth of Prostate Cancer Cells.

BACKGROUND: This study aims to test whether Cordyceps sinensis (CS), the most expensive Asian nutrient supplement might stimulate growth of prostate cancer cells. METHODS: Impact of CS on growth of prostate cancer was determined in vivo and in vitro. RESULTS: Firstly, the serum testosterone level was significantly elevated in mice fed CS. Prostate glands were significantly enlarged (weight index 0.53 ± 0.04 mg/g vs. 0.31 ± 0.04 mg/g, P = 0.006). Furthermore, cell viability was increased twofold in the androgen-responsive prostate cancer cell line (VCaP) after CS treatment. This promoting effect disappeared after bicalutamide was added. In addition, serum prostate-specific antigen (PSA) in mice bearing VCaP xenografts was significantly elevated (0.66 ± 0.04 ng/ml vs. 0.26 ± 0.06 ng/ml, P < 0.001) after treatment with CS. Finally, VCaP tumors in mice treated with CS grew much faster (479.2 ± 78.74 mm3 vs. 283 ± 58.97 mm3, P = 0.074). However, the above promoting effects of CS were not observed in parallel studies using the PC-3 cell line which lacks AR expression. CONCLUSIONS: These results suggest that CS promotes growth of prostate cancer cells by increasing production of testosterone and stimulating the AR-dependent pathway. Additional studies are required to see whether CS is safely consumed by patients with prostate cancer.

Computer aided design and three-dimensional printing for apicoectomy guide template / 北京大学学报(医学版)

OBJECTIVE@#To establish an apicoectomy guide template design and manufacturing method, based on multi-source data fusion, computer aided design (CAD) and fused deposition modeling (FDM). The feasibility of the guide template was preliminary evaluated by the in vitro model experiment.@*METHODS@#An extracted upper anterior tooth, after root canal treatment, was optical scanned, after which the extracted upper anterior tooth was poured in an apicoectomy plaster model. Cone-beam computed tomography (CBCT) scanning of the apicoectomy plaster model was performed, after which optical scanning of the plaster model for apical resection surgery was carried out. All of the relevant CBCT and optical scanning data of the extracted upper anterior tooth and the apicoectomy plaster model were introduced into the Geomagic Studio 2012 software. The multi-source data fusion technology was used to virtually simulate the three-dimensional positional relationship of the extracted tooth, the dentition, the alveolar bone and the gingival, based on which, the three-dimensional design of the apicoectomy guide template was completed in the Geomagic Studio 2012 software. With the technology of fused deposition modeling, the apical resection surgical guide template was three-dimensionally printed with the material of polylactic acid (PLA). Under the guidance of the surgical guide template, the root apical resection was performed on the plaster model. After the apicoectomy, the extracted upper anterior tooth was taken off from the apicoectomy plaster model and then was given the optical scanning. The apical resection length and angle were calculated by the function of distance measurement and angle measurement, and the results were compared with the preset values.@*RESULTS@#The length of the apical resection was 2.88 mm along the direction of the long axis of the tooth, which was 0.12 mm lower than the preset 3 mm. The included angle between the apical resection plane and the long axis of the tooth was 77.9°, 12.1° lower than the preset 90°.@*CONCLUSION@#This study successfully established a digital design and production method of apicoectomy guide template by combing the multi-source data fusion, CAD and FDM technology. The design route and the production method are feasible. The study will provide a technology and methodology reference for the development of domestic special software for the digital design of apicoectomy guide template.

Detection of root cracks after root canal preparation using rotary NiTi systems by optical coherence tomography (OCT) scan / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the accuracy of optical coherence tomography (OCT) in detecting root cracks after root canal instrumentation using histological gold standard.@*METHODS@#Twenty complete extracted human mandibular incisors that were free of caries, calculus, and root treatment were chosen and accessed coronally with a diamond bur, then mounted in resin blocks with alginate impression material using simulated periodontal ligaments, and the apex was exposed 3 mm. The teeth were stored in water at room temperature. Then the teeth were then instrumented to the major apical foramen (AF) at #30/0.09 using ProTaper Universal rotary nickel titanium system (Dentsply Maillefer, Ballaigues, Switzerland), irrigation with 1% sodium hypochlorite (NaOCl) by using a 26-gauge needle followed after each instrument. The apical root was scanned with 360° of rotation by Swept-Source Optical Coherence Tomography (SS-OCT) (wavelength: 1 310 nm, scan rate: 20 kHz, axial resolution: 16 μm) with driving device (stepper motor and lifting platform). The reconstruction images of axial planes 1, 2 and 3 mm from the apex were examined and the root cracks were blindly diagnosed by two observers. The horizontal section was performed at 1, 2 and 3 mm from the apex using low speed disc saw (Leica SP1600, Wetzlar, Germany). The presence of cracks was noted under an optical stereomicroscope (ZOOM-630E) with a cold light source using as gold standard to evaluate the accuracy of OCT in detecting root cracks after root canal instrumentation.@*RESULTS@#After canals instrumentation with ProTaper Universal rotary nickel titanium system to #30/0.09, root cracks were detected in 9 of 20 teeth by histological examination. Crack lines were observed on 13 of 60 horizontal sections and cracks on 12 of the 13 sections were detected by OCT. No cracks were observed in the other 47 of the 60 horizontal sections,none of which was misdiagnosed by OCT. The overall accuracy rate for detection of root cracks with OCT was 0.983, the sensitivity was 0.923, the specificity was 1.000, the positive predictive value (PPV) was 1.000 and the negative predictive value (NPV) was 0.979.@*CONCLUSION@#OCT may be a promising nondestructive imaging method for diagnosing root canal cracks after canal instrumentation.

A prognostic model for assessment of outcome of root canal treatment in teeth with pulpitis or apical periodontitis / 北京大学学报(医学版)

OBJECTIVE@#To present a prognostic model for evaluating the outcome of root canal treatment in teeth with pulpitis or apical periodontitis 2 years after treatment.@*METHODS@#The implementation of this study was based on a retrospective study on the 2-year outcome of root canal treatment. A cohort of 360 teeth, which received treatment and review, were chosen to build up the total sample size. In the study, 143 teeth with vital pulp and 217 teeth with apical periodontitis were included. About 67% of the samples were selected randomly to derive a training date set for modeling, and the others were used as validating date set for testing. Logistic regression models were used to produce the prognostic models. The dependent variable was defined as absence of periapical lesion or reduction of periapical lesion. The predictability of the models was evaluated by the area under the receiver-operating characteristic (ROC) curve (AUC).@*RESULTS@#Four predictors were included in model one (absence of apical lesion): pre-operative periapical radiolucency, canal curvature, density and apical extent of root fillings. The AUC was 0.802 (95%CI: 0.744-0.859). And the AUC of the testing date was 0.688. Only the density and apical extent of root fillings were included to present model two (reduction of apical lesion). The AUC of training dates and testing dates were 0.734 (95%CI: 0.612-0.856) and 0.681, respectively. As predicted by model one, the probability of absence of periapical lesion 2 years after endodontic treatment was 90% in pulpitis teeth with sever root-canal curvature and adequate root canal fillings, but 51% in teeth with apical periodontitis. When using prognostic model two for prediction, in teeth with apical periodontitis, the probability of detecting lesion reduction with adequate or inadequate root fillings was 95% and 39% 2 years after treatment.@*CONCLUSION@#The pre-operative periapical status, canal curvature and quality of root canal treatment could be used to predict the 2-year outcome of root canal treatment.

Cleaning efficacy of different solvents on sealer-contaminated dentin surface / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the influence of an epoxy resin-based sealer on the bond strength of adhesive resins to dentin and the cleaning efficacy of different solvents in removing sealer residues.@*METHODS@#The occlusal enamel of 25 freshly extracted human third molars without caries were removed to expose flat surfaces of dentin. The teeth were randomly divided into five groups according to the treatment received: For negative control group, the dentin surfaces were not contaminated with AH-Plus; For the other 4 experimental groups, the samples were contaminated with AH-Plus for 5 min and different measures were taken: For positive control group, the sealer were wiped with dry cotton pellets; For solvents experimental groups: cotton pellets saturated with 95% (volume fraction) ethanol, 99.5% (volume fraction) acetone or 99% (volume fraction) amyl acetate were used to wipe the sealer until the surface appeared clean when viewed through a stereomicroscope under ×10 magnification, then rinsed with de-ionized water for 3 s. After sealer removal, a self-etching adhesive system was applied on the surfaces with resin composite. The samples were sectioned into 1.0 mm×1.0 mm stick specimens (n=45) for microtensile test. Failure modes at the dentin-resin interface were observed using a stereomicroscope. The samples were sectioned into 1.0 mm piece specimens (n=4) for scanning electron microscope observation. The microtensile bond strength data were analyzed by one-way ANOVA. Chi-square test were used to analyse the failure modes between the groups.@*RESULTS@#There was significant difference among the five groups (P<0.001). For dry cotton pellet group (38.69±8.60) MPa and the ethanol group (37.14±12.01) MPa, the microtensile bond strength significantly declined when compared with negative control group (43.86±7.99) MPa (P<0.05). No significant difference of bond strength was found between the dry cotton pellet group and the ethanol group (P=0.426). There was no statistical significant difference among acetone group, amyl acetate group and negative control group (P>0.05). The bond strength of acetone group and amyl acetate group were (45.94±10.37) MPa and (43.99±7.01) MPa, respectively. The ethanol group exhibited lower bond strength than that of acetone group and amyl acetate group (P<0.05). Scanning electronic microscope observation revealed that in dry cotton pellet group and ethanol group, the resin tags were short and loose. Moreover, sealer residues were identified in the interface in the ethanol group samples, while the resin tags in the acetone and amyl acetate group were as dense and uniform as in negative control group. The distribution of failure modes showed no significant difference in the five groups (P=0.086).@*CONCLUSION@#The microtensile bond strength of dentin to composite resin was lower after exposure to sealer. Compared with ethanol and dry cotton pellets, the cleaning effect of acetone and amyl acetate on sealer-contaminated dentin surface were better.

Comparing the efficacy of induction-concurrent with concurrent-adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma: a propensity score matching analysis.

PURPOSE: This study aimed to compare the efficacy of induction-concurrent (IC-CCRT) with concurrent-adjuvant (CCRT-AC) chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated by intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Data on 834 patients with newly diagnosed, non-metastatic stage III-IVA (except T3N0) NPC receiving either IC-CCRT or CCRT-AC between July, 2004 and December, 2014 were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients. Survival outcomes of matched patients between IC-CCRT and CCRT-AC were compared. RESULTS: The median follow-up duration is 45.2 months (range, 1.07-145.4 months). Overall, 309 pairs were selected by PSM. Univariate analysis revealed the CCRT-AC group achieved significantly higher 3-year DFS (83.9% vs. 78.7 %; P = 0.014) and OS (87.6% vs. 87.0%; P = 0.031). Multivariate analysis also identified treatment group (IC-CCRT vs. CCRT-AC) as an independent prognostic factor for 3-year DFS (HR, 1.546; 95% CI, 1.113-2.149; P = 0.009) and OS (HR, 1.487; 95% CI, 1.035-2.136; P = 0.032). Subgroup analysis revealed IC-CCRT was a protective factor for DMFS (HR, 0.145; 95% CI, 0.043-0.488; P = 0.002) in stage III disease; however, it could adversely affected DFS (HR, 2.009; 95% CI, 1.316-3.065; P = 0.001), OS (HR, 1.671; 95% CI, 1.060-2.636; P = 0.027) and DMFS (HR, 1.986; 95% CI, 1.155-3.416; P = 0.013) in stage IVA disease. CONCLUSIONS: CCRT-AC may be a more effective treatment modality in patients with stage IVA NPC disease, while IC-CCRT was superior in stage III disease.

Prognostic value of chemotherapy in addition to concurrent chemoradiotherapy in T3-4N0-1 nasopharyngeal carcinoma: a propensity score matching study.

PURPOSE: The objective of this study is to evaluate the contribution of induction (IC) or adjuvant (AC) chemotherapy additional to concurrent chemoradiotherapy (CCRT) for patients with T3-4N0-1 nasopharyngeal carcinoma (NPC) in the era of intensity-modulate radiotherapy (IMRT). METHOD AND MATERIALS: We retrospectively reviewed the data on 685 patients with newly diagnosed T3-4N0-1 NPC. Propensity score matching (PSM) method was used to match patients. Survival outcomes between different groups were calculated by Kaplan-Meier method and compared using log-rank test. Cox proportional hazard model was adopted to establish independent prognostic factors. RESULTS: In total, 236 pairs were selected from the primary cohort. Univariate analysis revealed 3-year overall survival (OS) (90.8% vs. 90.3%, P = 0.820), distant failure-free survival (DFFS) (87.3% vs. 89.4%, P = 0.896) and locoregional failure-free survival (LRFFS) (95.4% vs. 93.0%, P = 0.311) rates were comparable between CCRT plus IC/AC and CCRT alone groups. Multivariate analysis found that treatment group was not an independent prognostic factors for OS (HR, 0.964; 95% CI, 0.620-1.499; P = 0.869), DFFS (HR, 1.036; 95% CI, 0.626-1.714; P = 0.890) and LRFFS (HR, 0.670; 95% CI, 0.338-1.327; P = 0.250). Further subgroup analysis according to overall stage also obtained similar results. CONCLUSION: Patients with T3-4N0-1 NPC receiving CCRT could not benefit from additional induction or adjuvant chemotherapy in the era of IMRT.

MicroRNA-19b-3p regulates nasopharyngeal carcinoma radiosensitivity by targeting TNFAIP3/NF-κB axis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is among the most common squamous cell carcinoma in South China and Southeast Asia. Radiotherapy is the primary treatment for NPC. However, radioresistance acts as a significant factor that limits the efficacy of radiotherapy for NPC patients. Growing evidence supports that microRNAs (miRNAs) play an important role in radiation response. METHODS: Real-time quantitative PCR was used to analyze the expression of miR-19b-3p in NPC cell lines and NP69. miR-19b-3p expression profiles in NPC tissues were obtained from the Gene Expression Omnibus database. The effect of miR-19b-3p on radiosensitivity was evaluated by cell viability assays, colony formation assays and in vivo experiment. Apoptosis and cell cycle were examined by flow cytometry. Luciferase reporter assay was used to assess the target genes of miR-19b-3p. Expression of target proteins and downstream molecules were analyzed by Western blot. RESULTS: miR-19b-3p was upregulated in NPC and served as an independent predictor for reduced patient survival. Radioresponse assays showed that miR-19b-3p overexpression resulted in decreased sensitivity to irradiation, whereas miR-19b-3p downregulation resulted in increased sensitivity to irradiation in vitro. Moreover, miR-19b-3p decreased the sensitivity of NPC cells to irradiation in vivo. Luciferase reporter assay confirmed that TNFAIP3 was a direct target gene of miR-19b-3p. Knockdown of TNFAIP3 reduced sensitivity to irradiation, whereas upregulation of TNFAIP3 expression reversed the inhibitory effects of miR-19b-3p on NPC cell radiosensitivity. Mechanistically, we found that miR-19b-3p increased NPC cell radioresistance by activating the TNFAIP3/ NF-κB axis. CONCLUSIONS: miR-19b-3p contributes to the radioresistance of NPC by activating the TNFAIP3/ NF-κB axis. miR-19b-3p is a determinant of NPC radioresponse and may serve as a potential therapeutic target in NPC treatment.

Pim-2 Modulates Aerobic Glycolysis and Energy Production during the Development of Colorectal Tumors.

Tumor cells have higher rates of glucose uptake and aerobic glycolysis to meet energy demands for proliferation and metastasis. The characteristics of increased glucose uptake, accompanied with aerobic glycolysis, has been exploited for the diagnosis of cancers. Although much progress has been made, the mechanisms regulating tumor aerobic glycolysis and energy production are still not fully understood. Here, we demonstrate that Pim-2 is required for glycolysis and energy production in colorectal tumor cells. Our results show that Pim-2 is highly expressed in colorectal tumor cells, and may be induced by nutrient stimulation. Activation of Pim-2 in colorectal cells led to increase glucose utilization and aerobic glycolysis, as well as energy production. While knockdown of Pim-2 decreased energy production in colorectal tumor cells and increased their susceptibility to apoptosis. Moreover, the effects of Pim-2 kinase on aerobic glycolysis seem to be partly dependent on mTORC1 signaling, because inhibition of mTORC1 activity reversed the aerobic glycolysis mediated by Pim-2. Our findings suggest that Pim-2-mediated aerobic glycolysis is critical for monitoring Warburg effect in colorectal tumor cells, highlighting Pim-2 as a potential metabolic target for colorectal tumor therapy.

[Long-term effect and safety of non-occlusive intra-vas device for male contraception].

OBJECTIVE: To assess the long-term effect and safety of non-occlusive intra-vas device (IVD) for male contraception in comparison with no-scalpel vasectomy (NSV). METHODS: We conducted a follow-up investigation on 100 males who had received IVD and another 50 who had undergone NSV 6 years before. We compared the rates of sperm absence and complications between the two groups. RESULTS: Follow-up visits were successfully performed on 95 males (95%) of the IVD group and 44 (88%) of the NSV group. Pregnancy was not found in any of the cases. Spermatozoa (> or = 5 x 10(6)/ml) were not detected in 87 cases (91.58%) in the IVD group and in 44 cases (95.45%) in the NSV group, with no significant differences between the two groups (P > 0.05). The rate of postoperative complications in the IVD group (11.58%) showed no significant difference from that of the NSV group (4.55%) (P > 0.05). CONCLUSION: IVD is as effective and safe as NSV for male contraception.

Inhibitory effects of limonin on six human cytochrome P450 enzymes and P-glycoprotein in vitro.

Among the various possible causes for drug interactions, pharmacokinetic factors such as inhibition of drug-metabolizing enzymes and transporters, especially cytochrome P450 (CYP) isoenzymes and P-glycoprotein (P-gp), are regarded as the most frequent and clinically important. Limonin is a widely used dietary supplement and one of the most prevalent citrus limonoids, which are known to have inhibitory effects on CYPs and P-gp. In this study, the in vitro inhibitory effects of limonin on the major human CYP isoenzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) activities in human liver microsomes were examined using liquid chromatography-tandem mass spectrometry. The inhibitory effects of limonin on P-gp activity in a human metastatic malignant melanoma cell line WM-266-4 were examined using a calcein-AM fluorometry screening assay. It demonstrates that limonin has negligible inhibitory effects on human CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and P-gp. However, potent inhibition of CYP3A4 by limonin is observed with IC50 values of 6.20 µM (CYP3A4/testosterone) and 19.10 µM (CYP3A4/midazolam). This finding has important implications with regard to food-drug interactions between limonin and several narrow therapeutic index drugs that are metabolized by CYP3A4.

In vitro inhibition of Huanglian [Rhizoma coptidis (L.)] and its six active alkaloids on six cytochrome P450 isoforms in human liver microsomes.

Huanglian (Rhizoma Coptidis) as a popular herb has been used for the treatment of various diseases such as diarrhea, eye inflammation and women's abdominal ailments. Alkaloids are considered to be responsible for its pharmacological effects. In this investigation, Huanglian and its six alkaloids (coptisine, epiberberine, berberine, jateorrhizine, palmatine and magnoflorine) were systematically evaluated for their inhibition of six cytochrome P450 isoforms (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in human liver microsomes by the LC-MS/MS method. Huanglian showed the strongest inhibition of CYP2D6, followed by CYP1A2 and CYP3A4_T. The IC50 values were 5.8 µg/mL, 36.8 µg/mL and 59.2 µg/mL, respectively. Of the constituents tested, coptisine and epiberberine showed strong inhibition of CYP2D6 with IC50 values of 4.4 µM and 7.7 µM; berberine, jateorrhizine and palmatine showed weak inhibition of CYP2D6 with IC50 values of 45.5 µM, 49.4 µM and 92.6 µM, respectively; jateorrhizine showed moderate inhibition of CYP3A4_T with an IC50 value of 13.3 µM; coptisine showed weak inhibition of CYP1A2 with an IC50 value of 37.3 µM. In addition, activation was observed in coptisine/CYP2C9 and palmatine/CYP2C9/CYP2C19. Other CYP450 isoforms were not affected markedly by the six alkaloids. In conclusion, Huanglian showed in vitro inhibition of CYP2D6, the inhibition might be contributed mostly by protoberberine alkaloids, especially coptisine and epiberberine. Herb-drug interactions may occur through the CYP2D6 inhibition.

[Effect of qihuang decoction on mRNA expressions of Bcl-2, Bax, and Caspase-3, 9 in intestinal mucosa epithelium of ischemia/reperfusion injured rats].

OBJECTIVE: To observe the effect of Qihuang Decoction (QHD) on mRNA expression of apoptosis genes Bcl-2, Bax, and signal transduction molecules Caspase-3, 9 in intestinal mucosa epithelium of ischemia/ reperfusion (I/R) injured rats. METHODS: Forty Wistar rats were randomized equally into 4 groups, the control group, the model group, the glutamine group, and the QHD group. Rats in the latter two groups were gastric infused with glutamine and QHD respectively for 3 days, but saline was infused instead to rats in the control group and model group. After then, except those in the control group intervened only by sham operation, rats were made into I/R injured model by 45 min occlusion of superior mesenteric artery followed by 1 h reperfusion. Immediately after modeling, mRNA expressions of Bcl-2, Bax, Caspase-3, and Caspase-9 in intestinal mucosa epithelium of rats were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with the control group, mRNA expressions of Bcl-2, Bax, Caspase-3 and Caspase-9 were higher in the other three groups (P < 0.05). Compared with the model group, Bcl-2 mRNA expression was higher, while the expressions of the other three indices were lower in both the glutamine group and the QHD group (P < 0.05); and comparisons between the glutamine group and the QHD group showed a more depressed Bax mRNA expression (0.281 +/- 0.087 vs 0.350 +/- 0.053) and higher Bcl-2/Bax ratio (1.648 vs 1. 374) in the QHD group. CONCLUSIONS: QHD can reduce the I/R injury in the intestinal mucosa epithelium by inhibiting the cell apoptosis. The mechanism may be correlated with increased Bcl-2 mRNA expressions and decreased mRNA expressions of Bax, Caspase-3 and Caspase-9.

[Effect of qihuang decoction on epithelial cell apoptosis of ischemia/reperfusion injured intestinal mucosa in rat].

OBJECTIVE: To observe the effect of Qihuang Decoction (QHD) on epithelial cell apoptosis of ischemia-reperfusion (I/R) injured intestinal mucosa in rat. METHODS: The I/R injured intestinal mucosa rat model was established by clamping superior mesenteric artery (SMA) for 45 min and reperfusing for 60 min. The pathomorphological Changes and epithelial cell apoptosis in the injured intestinal mucosa were observed and compared among groups: the sham-operated group (A), the model group (B), the glutamine treated group (C) and the QHD treated group (D). RESULTS: pathomorphological examination showed that in group A, the intestinal villus was intact; in group B, the intestinal subepithelial space were dilated, and showed evident cleavage between the epithelial top and the lamina propria with bare capillaries, bleeding and ulceration; in group C and D, the above-mentioned pathomorphological changes were alleviated to some extents, appeared only in part of the villa, and the alleviation was more significant in group D than in group C. Chiu's scoring showed that the lowest score (zero) presented in group A and the highest presented in group B; scores in group C and D was significantly lower than that in group B (P < 0.05), but showed insignificant difference between the two groups (P > 0.05). Epithelial cell apoptosis detection showed that the least apoptosis rate presented in group A, and the highest in the group B; while in the group C, it lied between group A and B (all P < 0.05), and showed no statistical significance to group D (P > 0.05), though appeared a lowering trend. CONCLUSION: QHD could reduce the I/R injured intestinal epithelial mucosa, and its protective mechanism may be related to the inhibition on apoptosis of intestinal mucosal epithelial cells.