Predicting coronary artery calcified plaques using perivascular fat CT radiomics features and clinical risk factors.

OBJECTIVE: The purpose of this study was to develop a combined radiomics model to predict coronary plaque texture using perivascular fat CT radiomics features combined with clinical risk factors. METHODS: The data of 200 patients with coronary plaques were retrospectively analyzed and randomly divided into a training group and a validation group at a ratio of 7:3. In the training group, The best feature set was selected by using the maximum correlation minimum redundancy method and the least absolute shrinkage and selection operator. Radiomics models were built based on different machine learning algorithms. The clinical risk factors were then screened using univariate logistic regression analysis. and finally a combined radiomics model was developed using multivariate logistic regression analysis to combine the best performing radiomics model with clinical risk factors and validated in the validation group. The efficacy of the model was assessed by a receiver operating characteristic curve, the consistency of the nomogram was assessed using calibration curves, and the clinical usefulness of the nomogram was assessed using decision curve analysis. RESULTS: Twelve radiomics features were used by different machine learning algorithms to construct the radiomics model. Finally, the random forest algorithm built the best radiomics model in terms of efficacy, and this was combined with age to construct a combined radiomics model. The area under curve for the training and validation group were 0.98 (95% confidence interval, 0.95-1.00) and 0.97 (95% confidence interval, 0.92-1.00) with sensitivities of 0.92 and 0.86 and specificities of 0.99 and 1, respectively. The calibration curve demonstrated that the nomogram had good consistency, and the decision curve analysis demonstrated that the nomogram had high clinical utility. CONCLUSIONS: The combined radiomics model established based on CT radiomics features and clinical risk factors has high value in predicting coronary artery calcified plaque and can provide a reference for clinical decision-making.

Final Overall Survival Analysis of Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma: A Multicenter, Randomized Phase III Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported significantly improved failure-free survival using gemcitabine plus cisplatin induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized trial, patients were assigned to be treated with concurrent chemoradiotherapy alone (standard therapy, n = 238) or gemcitabine and cisplatin induction chemotherapy before concurrent chemoradiotherapy (n = 242). With a median follow-up of 69.8 months, the induction chemotherapy group had a significantly higher 5-year OS (87.9% v 78.8%, hazard ratio, 0.51 [95% CI 0.34 to 0.78]; P = .001) and a comparable risk of late toxicities (≥ grade 3, 11.3% v 11.4%). Notably, the depth of the tumor response to induction chemotherapy correlated significantly and positively with survival (complete response v partial response v stable/progressive disease, 5-year OS, 100% v 88.4% v 61.5%, P = .005). Besides, patients with a low pretreatment cell-free Epstein-Barr virus DNA load (< 4,000 copies/mL) might not benefit from induction chemotherapy (5-year OS, 90.6% v 91.4%, P = .77). In conclusion, induction chemotherapy before concurrent chemoradiotherapy improved OS significantly in patients with locally advanced nasopharyngeal carcinoma, without increasing the risk of late toxicities. Tumor response to induction chemotherapy and pretreatment cell-free Epstein-Barr virus DNA might be useful to guide individualized treatment.

Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111. FINDINGS: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group. INTERPRETATION: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma. FUNDING: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Road traffic injury mortality and morbidity by country development status, 2011-2017.

PURPOSE: This research examined road traffic injury mortality and morbidity disparities across of country development status, and discussed the possibility of reducing country disparities by various actions to accelerate the pace of achieving Sustainable Development Goals target 3.6 - to halve the number of global deaths and injuries from road traffic accidents by 2020. METHODS: Data for road traffic mortality, morbidity, and socio-demographic index (SDI) were extracted by country from the estimates of the Global Burden of Disease study, and the implementation of the three types of national actions (legislation, prioritized vehicle safety standards, and trauma-related post-crash care service) were extracted from the Global Status Report on Road Safety by World Health Organization. We fitted joinpoint regression analysis to identify and quantify the significant rate changes from 2011 to 2017. RESULTS: Age-adjusted road traffic mortality decreased substantially for all the five SDI categories from 2011 to 2017 (by 7.52%-16.08%). Age-adjusted road traffic mortality decreased significantly as SDI increased in the study time period, while age-adjusted morbidity generally increased as SDI increased. Subgroup analysis by road user yielded similar results, but with two major differences during the study period of 2011 to 2017: (1) pedestrians in the high SDI countries experienced the lowest mortality (1.68-1.90 per 100,000 population) and morbidity (110.45-112.72 per 100,000 population for incidence and 487.48-491.24 per 100,000 population for prevalence), and (2) motor vehicle occupants in the high SDI countries had the lowest mortality (4.07-4.50 per 100,000 population) but the highest morbidity (428.74-467.78 per 100,000 population for incidence and 1025.70-1116.60 per 100,000 population for prevalence). Implementation of the three types of national actions remained nearly unchanged in all five SDI categories from 2011 to 2017 and was consistently stronger in the higher SDI countries than in the lower SDI countries. Lower income nations comprise the heaviest burden of global road traffic injuries and deaths. CONCLUSION: Global road traffic deaths would decrease substantially if the large mortality disparities across country development status were reduced through full implementation of proven national actions including legislation and law enforcement, prioritized vehicle safety standards and trauma-related post-crash care services.

Global road traffic injury statistics: Challenges, mechanisms and solutions.

High-quality data are the foundation to monitor the progress and evaluate the effects of road traffic injury prevention measures. Unfortunately, official road traffic injury statistics delivered by governments worldwide, are often believed somewhat unreliable and invalid. We summarized the reported problems concerning the road traffic injury statistics through systematically searching and reviewing the literature. The problems include absence of regular data, under-reporting, low specificity, distorted cause spectrum of road traffic injury, inconsistency, inaccessibility, and delay of data release. We also explored the mechanisms behind the problematic data and proposed the solutions to the addressed challenges for road traffic statistics.

Breakup Dynamics of Semi-dilute Polymer Solutions in a Microfluidic Flow-focusing Device.

Droplet microfluidics involving non-Newtonian fluids is of great importance in both fundamental mechanisms and practical applications. In the present study, breakup dynamics in droplet generation of semi-dilute polymer solutions in a microfluidic flow-focusing device were experimentally investigated. We found that the filament thinning experiences a transition from a flow-driven to a capillary-driven regime, analogous to that of purely elastic fluids, while the highly elevated viscosity and complex network structures in the semi-dilute polymer solutions induce the breakup stages with a smaller power-law exponent and extensional relaxation time. It is elucidated that the elevated viscosity of the semi-dilute solution decelerates filament thinning in the flow-driven regime and the incomplete stretch of polymer molecules results in the smaller extensional relaxation time in the capillary-driven regime. These results extend the understanding of breakup dynamics in droplet generation of non-Newtonian fluids and provide guidance for microfluidic synthesis applications involving dense polymeric fluids.

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.

BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).

Long noncoding RNA UBE2R2-AS1 promotes glioma cell apoptosis via targeting the miR-877-3p/TLR4 axis.

Introduction: Brain glioma is the most common type of primary malignancy in the central nervous system (CNS), with high recurrence and mortality rate, especially glioblastoma (GBM). Recent evidence suggests a role for many long noncoding RNAs (lncRNAs) in the pathogenesis, proliferation, apoptosis, metastasis, and chemotherapeutic resistance of cancer cells. Although the functions of some lncRNAs in the occurrence and development of gliomas have been confirmed, detailed mechanisms of action are lacking. Furthermore, the biological roles of many other lncRNAs in glioma have not been reported at all. Methods: In this study, we identified a novel lncRNA, UBE2R2-AS1, which was dramatically downregulated in glioma compared with normal tissue, by performing microarray detection of six pairs of glioma samples and adjacent normal tissues. In vitro experiments demonstrated that UBE2R2-AS1 regulated glioma cell proliferation, apoptosis, and migration. Results: UBE2R2-AS1 acted as a competing endogenous RNA (ceRNA) to target Toll-like receptor 4 (TLR4) mRNA by binding to miR-877-3p. Furthermore, lncRNA UBE2R2-AS1 suppressed glioblastoma cell growth, migration, and invasion, as well as promoting cell apoptosis by targeting miR-877-3p/TLR4 directly. Conclusion: This information regarding UBE2R2-AS1 and its glioma-related molecular mechanisms will aid the future identification of new lncRNA-directed diagnostics and drug-targeting therapies.

Left-turning vehicle-pedestrian conflicts at signalized intersections with traffic lights: Benefit or harm? A two-stage study.

PURPOSE: Vehicle-pedestrian conflicts are common at road intersections when traffic lights change. However, the impact of traffic light on transportation safety and efficiency remains poorly understood. METHODS: A two-stage study was used to survey the proportion of intersections with conflicting traffic lights and the related transportation efficiency and safety were evaluated as well. First, a cross-sectional study estimated the proportion of signalized intersections with conflicting left-turning vehicle-pedestrian traffic lights in Changsha city, China. Second, a natural experiment compared transportation efficiency and safety between intersections with and without conflicting left-turning vehicle-pedestrian traffic lights. Risky conflicts, where motor vehicles violated laws and failed to yield to pedestrians in crosswalk were used as a surrogate for transportation safety. The number of motor vehicles and pedestrians passing through the intersections per second and per meter were used to estimate transportation efficiency. Data were collected and analyzed in 2015 (from March to December). A search of online news from domestic media sources was also conducted to collect pedestrian injury data occurring at the intersections. RESULTS: About one-fourth (57/216) intersections had conflicting left-turning traffic lights (95% CI: 20.5%, 32.3%). Risky vehicle-pedestrian conflicts were more frequently observed at intersections with conflicting lights compared to those without (incidence rate ratio (IRR) = 3.13; pedestrians: IRR = 4.02), after adjusting for type of day (weekday vs. weekend), the time period of observation, and motor vehicles traffic flow. Intersections without conflicting vehicle-pedestrian traffic lights had similar transportation efficiency to those with conflicting lights after controlling for covariates (p > 0.05). The systematic review of news media reports yielded 10 left-turning vehicle-pedestrian crash events between 2011 and 2017, involving 11 moderate or severe pedestrian injuries and 3 fatal pedestrian injuries. CONCLUSION: Over one-fourth of road intersections in Changsha city, China have conflicting left-turning traffic lights. Conflicting traffic lights cannot improve transportation efficiency, but increase risky conflicts between vehicles and pedestrians.

Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Long-term results of phase 3 randomized controlled trial.

To report long-term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III-IVB (except T3-4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m2 d1), cisplatin (60 mg/m2 d1), and fluorouracil (600 mg/m2 /d civ d1-5) every 3 weeks. Patients from both groups received intensity-modulated radiotherapy concurrently with three cycles of 100 mg/m2 cisplatin every 3 weeks. After a median follow-up of 71.5 months, the IC plus CCRT group showed significantly better 5-year failure-free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure-free survival (88% vs. 79.8%, p = 0.030), and locoregional failure-free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein-Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long-term follow-up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.

Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial.

AIM OF THE STUDY: Previous results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC). METHODS: Patients with stage III-IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m2 weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m2 and fluorouracil 800 mg/m2/d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival. RESULTS: Two hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64-1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3-4 toxicities (p = 0.14). CONCLUSION: Adjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities. REGISTRATION NUMBER: NCT00677118.

Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial.

BACKGROUND: The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial. METHODS: We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III-IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18-59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m2 on day 1), intravenous cisplatin (60 mg/m2 on day 1), and continuous intravenous fluorouracil (600 mg/m2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT01245959. FINDINGS: Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38-49), 3-year failure-free survival was 80% (95% CI 75-85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66-78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48-0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 [42%] vs 17 [7%]), leucopenia (98 [41%] vs 41 [17%]), and stomatitis (98 [41%] vs 84 [35%]). INTERPRETATION: Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities. FUNDING: Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000).

[C:N:P stoichiometry characteristics of litter and soil of forests in Great Xing'an Mountains with different fire years.] / å¤§å ´å®‰å²­ä¸åŒç«çƒ§å¹´é™æ£®æž—å‡‹è½ç‰©å’ŒåœŸå£¤C、N、P化学计量特征.

We investigated the fire impacts on nutrients in litter and soil, and their C:N:P stoichio-metry in forests of Great Xing'an Mountains. The studied sites differed in their burning year (post-fire 4, 14, 40, 70 years and unburned within 120 years) and had different topographic locations (sloped land and flat land). The results showed that there were significant differences in stoichio-metry characteristics of C, N, P for both litter and soil with different burning years. No significant fluctuation was observed for the litter C content, while the contents of litter N and P increased with the increasing post-fire recovery years. In specific, we found the contents of litter N and P decreased at post-fire 4 and 14 years and nearly recovered to the control level at 40 years after fire. Additionally, C:N and C:P ratios of litter decreased, but N:P ratio of litter increased following post-fire recovery time. The contents of C, N, P and their ratios (C:N, C:P and N:P) in soil decreased with soil depth. Soil C content exhibited an increasing trend following post-fire recovery time and was significantly higher than the control at post-fire 70 years in sloped land, but no significant difference in the flat land. Significant interactive effects between fire history and slope were observed in soil P content and C:P ratio. Soil P content was higher than the control at post-fire 4 years in sloped land, but was higher than the control at post-fire 40 years in flat land. The C:P ratio recovered to the control level at post-fire 14 years in sloped land, and there was no significant diffe-rence in flat land. Redundancy analysis showed that slope effect played a more vital role than fire history effect in soil organic layer, while fire history effect was the most important factor for the varia-tion of soil nutrients in soil mineral layer. In our study, nutrients of litter and soil were lower than the control level at post-fire 4 and 14 years. The quality of litter and soil was improved with accele-rated plant growth and litter decomposition following post-fire recovery time and recovered to the pre-fire level at post-fire 40 years, reaching a steady status.

Anticancer effects of celecoxib through inhibiton of STAT3 phosphorylation and AKT phosphorylation in nasopharyngeal carcinoma cell lines.

Previously, we showed that treatment with celecoxib obviously inhibited proliferation of nasopharyngeal carcinoma (NPC) cell lines in a dose-dependent manner. However, the underlying molecular mechanisms of its anticancer effect on NPC have not been fully clarified. The present in vitro study was performed to investigate the mechanisms involved in the anticancer effect of celecoxib in NPC. NPC cell line HONE1 was treated with celecoxib at varying concentrations. The antiproliferation effect of celecoxib on the HONE1 cell line was assessed with methyl thiazolyl tetrazolium (MTT) assay. Western blot analysis of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3(Y705) (pSTAT3(Y705)), Survivin, Mcl-1, Bcl-2 and Cyclin D1 was carried out at various concentration of celecoxib for 48 h in HONE1 cell line. Western blot analysis of Protein Kinase B (AKT), phosphorylated AKT (pAKT) was performed at increasing doses of celecoxib for 48 h in HNE1, CNE1-LMP1 and HONE1 cells. The results showed that celecoxib inhibited proliferation of HONE1 cell line in a dose-dependent manner. Celecoxib inhibited the activation of STAT3 phosphorylation in HONE1 cells and the downstream genes of STAT3 (Survivin, Mcl-1, Bcl-2 and Cyclin D1) were downregulated after treatment with celecoxib. Furthermore, celecoxib could inhibit AKT phosphorylation in HNE1, CNE1-LMP1 and HONE1 cell lines. These data suggested that celecoxib was a promising agent for the chemoprevention and treatment of NPC.

Single-arm, multi-centre phase II study of lobaplatin combined with docetaxel for recurrent and metastatic nasopharyngeal carcinoma patients.

OBJECTIVES: The primarily aim of this phase II study is to evaluate the response rate (RR) and disease control rate (DCR). The secondary aim of this study is to assess the progression-free survival and overall survival of recurrent or metastatic nasopharyngeal carcinoma (NPC) patients treated with lobaplatin in combination with docetaxel. MATERIALS AND METHODS: Patients with recurrent and metastatic NPC received docetaxel (75 mg/m(2) on day 1) and lobaplatin (30 mg/m(2) on day 2) every 3 weeks for two to six courses. RESULTS: From April 2011 to July 2013, 39 patients were enrolled. In total, 3 patients (7.7%) had complete response, 21 (53.8%) had partial response, 9 (23.1%) had stable disease and 4 (10.3%) had progressive disease. The overall RR was 61.5% (95% CI, 46.2-76.8%), and the DCR was 84.6% (95% CI, 73.3-95.9%). The median time to progression was 10 months (95% CI, 7.3-12.8 months) after the median follow-up duration of 10.3 months (1.5-28.9 months). The most common grade 3/4 toxicities included leucopaenia and neutropaenia (17.9%), anaemia (5.1%) and increased aminotransferase level (2.6%). Other toxicities were grade 1/2 and minimal. CONCLUSION: Lobaplatin in combination with docetaxel demonstrated clinical activity and an acceptable toxicity profile in recurrent and metastatic NPC patients. Lobaplatin may be effective for recurrent and metastatic NPC patients who previously received cisplatin-based chemotherapy.

Interleukin-6 promotes the migration and invasion of nasopharyngeal carcinoma cell lines and upregulates the expression of MMP-2 and MMP-9.

Nasopharyngeal carcinoma (NPC) shows the highest invasive and metastatic features among head and neck cancers. Distant metastasis remains the predominant mode of treatment failure in NPC patients. The role of interleukin-6 (IL-6) in NPC progression is not fully understood. In this study, we explored whether IL-6 could promote the migration and invasion activity of NPC cell lines, as well as whether the effect of IL-6 on cell migration and invasion is mediated through regulating the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. Our results revealed that IL-6 and its receptors are broadly expressed in various NPC cell lines including HNE1, HONE1, CNE1, CNE1-LMP1 and 5-8F. Exogenous IL-6 enhanced cell proliferation slightly, but promoted cell migration and invasion significantly in both HNE1 and CNE1-LMP1 cell lines. In addition, an elevation in the expression of MMP-2 and MMP-9 could be induced by IL-6 stimulation. On the contrary, combining treatment with monoclonal anti-human IL-6R antibody (anti-IL-6R mAb) resulted in decreased proliferation, migration and invasion capabilities of NPC cells. Anti-IL-6R mAb also inhibited the expression of MMP-2 and MMP-9 in IL-6-stimulated HNE1 and CNE1-LMP1 cells. In summary, our data suggested that IL-6 mainly promotes the cell migration and invasion of NPC cells. The effect of IL-6 on cell migration and invasion may be mediated through regulation of the expression of MMP-2 and MMP-9. Thus, IL-6 or its related signaling pathways may be a promising target for preventing and inhibiting NPC metastasis.

Cyclooxygenase-2 inhibitor celecoxib suppresses invasion and migration of nasopharyngeal carcinoma cell lines through a decrease in matrix metalloproteinase-2 and -9 activity.

Celecoxib is a selective inhibitor of COX-2, whose connection with the development and progression of human tumors has been extensively studied. So far, however, its anti-metastatic effect is poorly understood in nasopharyngeal carcinoma. The current study aimed to observe the effect of celecoxib on invasion and migration of nasopharyngeal carcinoma cell lines and investigate the potential mechanism in vitro. Human nasopharyngeal carcinoma cell lines HNE1, HONE1, SUNE1-5-8F were exposed to different concentrations of celecoxib. MTT assay was used to study its anti-proliferation effect, transwell assay wound healing repair assay were performed to investigate the invasiveness and migration capability after treatment with celecoxib. The activity of MMP-2 and MMP-9 was measured by gelatin zymography. MTT assay showed that celecoxib inhibited HNE1, HONE1, and SUNE1-5-8F cells growth. Wound healing repair assay and transwell assay showed that cell metastatic ability was suppressed after treatment with celecoxib. Celecoxib had a significant inhibitory effect on the activity of MMP-2/9 in a dose-dependent manner in HNE1, HONE1 and SUNE1-5-8F cell lines. These data demonstrated that celecoxib-induced suppression of MMP-2 and MMP-9 activity might be involved in the inhibition of nasopharyngeal carcinoma cell lines invasion and migration.

Pedestrian mortality between 2006 and 2010 in China: findings from non-police reported data.

Pedestrian safety in China is an important but largely neglected issue, in part due to the substantial under-reporting within police data. In this study we aimed to examine changes in pedestrian fatality between 2006 and 2010 in China using non-police reported data. A multi-year study was conducted based on the mortality data during 2006-2010 from the Disease Surveillance Points (DSP) data in China. Between 2006 and 2010, the crude pedestrian mortality increased from 7.0 to 10.5 per 100 000 populations. Annual pedestrian mortality from DSP data was 13 times in 2006 and 55 times in 2010 mortality for pedestrians and passengers from police-reported data in the corresponding years. After controlling for sex, age, and urban/rural, the mortality increased by 44% from 2006 to 2010 (adjusted mortality rate ratio (MRR)=1.11, 95% CI 1.10-1.12). The problem of pedestrian deaths is much more serious in China than that officially reported by the police. Significant and urgent efforts are needed to save lives of pedestrian in China.