Publications by authors named "Guo-Qing Hu"

39 Publications

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

Lancet 2021 Jun 4. Epub 2021 Jun 4.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.

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/m 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.
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http://dx.doi.org/10.1016/S0140-6736(21)01123-5DOI Listing
June 2021

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

Chin J Traumatol 2021 Mar 19;24(2):88-93. Epub 2021 Jan 19.

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, 410078, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.cjtee.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071733PMC
March 2021

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

Chin J Traumatol 2020 Aug 19;23(4):216-218. Epub 2020 Jun 19.

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, 410078, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.cjtee.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451583PMC
August 2020

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

Micromachines (Basel) 2020 Apr 14;11(4). Epub 2020 Apr 14.

School of Optoelectronic Engineering and Instrumentation Science, Dalian University of Technology, Dalian 116024, China.

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.
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http://dx.doi.org/10.3390/mi11040406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231330PMC
April 2020

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.

N Engl J Med 2019 09 31;381(12):1124-1135. Epub 2019 May 31.

From the Departments of Radiation Oncology (Y.Z., L.C., Y.-P.C., W.-H.H., W.-F.L., L.-L.T., Y.-P.M., G.-Q.Z., R.S., X.L., R.G., F.H., J.-W.L., X.-J.D., C.X., N.L., Y.-Q.L., F.-Y.X., Ying Sun, J.M.), Medical Oncology (Y.-H.L.), and Nasopharyngeal Carcinoma (H.-Y.M.) and the Clinical Trials Center (Y.G.), Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy (Y.Z., L.C., Y.-P.C., W.-H.H., W.-F.L., L.-L.T., Y.-P.M., G.-Q.Z., R.S., X.L., R.G., F.H., J.-W.L., X.-J.D., C.X., N.L., Y.-Q.L., F.-Y.X., Ying Sun, J.M.), and the Department of Radiation Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University (X.-C.W., Q.-F.S.), Guangzhou, the Cancer Center, Tongji Hospital Affiliated to Tongji Medical College (G.-Q.H., G.-X.L.), and the Cancer Center, Union Hospital, Tongji Medical College (K.-Y.Y., J.H.), Huazhong University of Science and Technology, Wuhan, the Department of Radiation Oncology, First People's Hospital of Foshan, Foshan (N.Z., S.-Q.L.), the Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning (X.-D.Z., L.L.), the Department of Head and Neck Oncology, Affiliated Hospital of Guizhou Medical University, Guizhou Cancer Hospital, Guiyang (F.J., J.-H.L.), the Department of Radiation Oncology, XiJing Hospital of Fourth Military Medical University, Xi'an (M.S., J.Z.), the Cancer Center (Z.-B.C.), and the Department of Head and Neck Oncology (S.-Y.W., Q.-D.L.), Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, the Department of Radiation Oncology, Second Affiliated Hospital of Soochow University, Suzhou (Y.T., L.Z.), the Department of Radiation Oncology, Peking University Cancer Hospital, Beijing (Yan Sun, B.-M.Z.), and the Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang (J.-G.L., Y.X.) - all in China; and the Divisions of Radiation Oncology and Medical Sciences, National Cancer Center Singapore, and the Oncology Academic Program, Duke-National University of Singapore Medical School - both in Singapore (M.L.K.C.).

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.).
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http://dx.doi.org/10.1056/NEJMoa1905287DOI Listing
September 2019

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

Onco Targets Ther 2019 7;12:3467-3480. Epub 2019 May 7.

Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.

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. 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. 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. 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.
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http://dx.doi.org/10.2147/OTT.S201732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511244PMC
May 2019

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

Chin J Traumatol 2019 Apr 11;22(2):63-68. Epub 2019 Mar 11.

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.cjtee.2018.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488518PMC
April 2019

Incidence of Interpersonal Violence among Individuals with Drug Addiction Receiving Compulsory Treatment: A Survey at Two Drug Detention Centers in Hunan, China.

Biomed Environ Sci 2018 Dec;31(12):883-887

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan, China.

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http://dx.doi.org/10.3967/bes2018.119DOI Listing
December 2018

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

Int J Cancer 2019 07 24;145(1):295-305. Epub 2019 Jan 24.

Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, People's Republic of China.

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/m d1), cisplatin (60 mg/m d1), and fluorouracil (600 mg/m /d civ d1-5) every 3 weeks. Patients from both groups received intensity-modulated radiotherapy concurrently with three cycles of 100 mg/m 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.
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http://dx.doi.org/10.1002/ijc.32099DOI Listing
July 2019

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

Eur J Cancer 2017 04 22;75:150-158. Epub 2017 Feb 22.

State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China. Electronic address:

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/m weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m and fluorouracil 800 mg/m/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.
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http://dx.doi.org/10.1016/j.ejca.2017.01.002DOI Listing
April 2017

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

Lancet Oncol 2016 Nov 27;17(11):1509-1520. Epub 2016 Sep 27.

Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

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/m cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m on day 1), intravenous cisplatin (60 mg/m on day 1), and continuous intravenous fluorouracil (600 mg/m 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).
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http://dx.doi.org/10.1016/S1470-2045(16)30410-7DOI Listing
November 2016

[C:N:P stoichiometry characteristics of litter and soil of forests in Great Xing'an Mountains with different fire years.]

Ying Yong Sheng Tai Xue Bao 2016 May;27(5):1359-1367

Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110164, China.

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.
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http://dx.doi.org/10.13287/j.1001-9332.201605.030DOI Listing
May 2016

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

Pharmazie 2014 May;69(5):358-61

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.
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May 2014

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

Oral Oncol 2014 Aug 17;50(8):717-20. Epub 2014 May 17.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, Hubei, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.oraloncology.2014.04.007DOI Listing
August 2014

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

Pharmazie 2014 Feb;69(2):132-7

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.
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February 2014

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

Int J Oncol 2014 May 5;44(5):1551-60. Epub 2014 Mar 5.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan 430030, P.R. China.

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.
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http://dx.doi.org/10.3892/ijo.2014.2323DOI Listing
May 2014

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

Biomed Environ Sci 2013 Oct;26(10):853-6

Johns Hopkins International Injury Research Unit, Johns Hopkins Bloomberg School of Public Health, Baltimore 21205, MD, USA.

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.
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http://dx.doi.org/10.3967/bes2013.009DOI Listing
October 2013

Specific targeting of angiogenesis in lung cancer with RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a 4.7T magnetic resonance scanner.

Chin Med J (Engl) 2013 Jun;126(12):2242-7

Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.

Background: Angiogenesis is an essential step for tumor development and metastasis. The cell adhesion molecule avβ3 integrin plays an important role in angiogenesis and is a specific marker of tumor angiogenesis. A novel avβ3 integrin- targeted magnetic resonance (MR) imaging contrast agent utilizing Arg-Gly-Asp (RGD) and ultrasmall superparamagnetic iron oxide particles (USPIO) (referred to as RGD-USPIO) was designed and its uptake by endothelial cells was assessed both in vitro and in vivo to evaluate the angiogenic profile of lung cancer.

Methods: USPIO were coated with -NH3+ and conjugated with RGD peptides. Prussian blue staining was performed to evaluate the specific uptake of RGD-USPIO by human umbilical vein endothelial cells (HUVECs). Targeted uptake and subcellular localization of RGD-USPIO in HUVECs were confirmed by transmission electron microscopy (TEM). The ability of RGD-USPIO to noninvasively assess avβ3 integrin positive vessels in lung adenocarcinoma A549 tumor xenografts was evaluated with a 4.7T MR scanner. Immunohistochemistry was used to detect avβ3 integrin expression and vessel distribution in A549 tumor xenografts.

Results: HUVECs internalized RGD-USPIO significantly more than plain USPIO. The uptake of RGD-USPIO by HUVECs could be competitively inhibited by addition of free RGD. A significant decrease in T2 signal intensity (SI) was observed at the periphery of A549 tumor xenografts at 30 minutes (P < 0.05) and 2 hours (P < 0.01) after RGD-USPIO was injected via the tail vein. Angiogenic blood vessels were mainly distributed in the periphery of tumor xenografts with positive avβ3 integrin expression.

Conclusions: RGD-USPIO could specifically label avβ3 integrin and be taken up by HUVECs. This molecular MR imaging contrast agent can specifically evaluate the angiogenic profile of lung cancer using a 4.7T MR scanner.
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June 2013

Epidemiological survey of the prevalence of non-fatal injury among children aged 5-14 years in China.

Biomed Environ Sci 2012 Aug;25(4):407-12

Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha 410078, Hunan, China.

Objective: To determine the prevalence of non-fatal injuries among children aged 5-14 years in China.

Methods: Data of 21 973 children aged 5-14 years were extracted from the Fourth National Health Service Survey of China carried out between June 15 and July 10, 2008. Injury-related indicators included: history of ever having had an injury, and injury frequency, cause, location and severity.

Results: The overall prevalence of non-fatal injuries among the children in the previous 12 months was 17.0 per 1000 subjects. The leading causes of non-fatal injuries were falls, animal bites, traffic accidents, falling objects and burns. The majority of children sustained only one injury. The main place of injury was at home in 40% and 54% of urban boys and girls, respectively, at school in 48% of rural boys, and at home and at school each in 33% of rural girls. Medical treatment for one day was the main option for 80% of urban boys and girls, 84% of rural boys, and 72% of rural girls.

Conclusion: Nonfatal injuries among children aged 5-14 years are a serious public health concern in China.
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http://dx.doi.org/10.3967/0895-3988.2012.04.005DOI Listing
August 2012

Decreased expression of the carboxyl terminus of heat shock cognate 70 interacting protein in human gastric cancer and its clinical significance.

Oncol Rep 2012 Oct 8;28(4):1392-8. Epub 2012 Aug 8.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.

The carboxyl terminus of heat shock cognate 70 interacting protein (CHIP) is an E3 ubiquitin ligase, which can promote ubiquitylation and degradation of many tumor-related proteins. However, the expression of CHIP in human gastric cancer has not been investigated. In this study, the mRNA and protein levels of CHIP expression in 53 cases of gastric cancer and matched normal tissues were determined by quantitative real-time PCR, western blotting and immunohistochemistry. We showed that CHIP was registered from basal to middle portions of normal gastric mucosa. CHIP expression was notably decreased or lost in human gastric cancer samples compared with the matched normal non-cancer samples. The correlations between CHIP downregulation and the clinicopathological characteristics were also evaluated. The expression of CHIP was significantly lower in the gastric cancer samples compared to the matched normal samples at both mRNA and protein levels (P<0.05 and P<0.05, respectively). More importantly, the downregulation of CHIP was correlated with TNM stage (P=0.048) and lymph node metastasis (P=0.010) at the mRNA levels. In addition, the downregulation of CHIP was correlated with lymph node metastasis (P=0.021) and tumor differentiation (P=0.009) at the protein levels. Taken together, at both mRNA and protein levels, the decreased expression of CHIP was correlated with lymph node metastasis. Furthermore, our study suggests that a negative correlation exists between CHIP expression and tumor malignancy in human gastric cancer.
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http://dx.doi.org/10.3892/or.2012.1957DOI Listing
October 2012

Epidermal growth factor receptor-targeted ultra-small superparamagnetic iron oxide particles for magnetic resonance molecular imaging of lung cancer cells in vitro.

Chin Med J (Engl) 2012 Jul;125(13):2322-8

Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.

Background: Magnetic resonance (MR) molecular imaging can detect abnormalities associated with disease at the level of cell and molecule. The epidermal growth factor receptor (EGFR) plays an important role in the development of lung cancer. This study aimed to explore new MR molecular imaging targeting of the EGFR on lung cancer cells.

Methods: We attached ultra-small superparamagnetic iron oxide (USPIO) particles to cetuximab (C225) anti-human IgG using the carbodiimide method. We made the molecular MR contrast agents C225-USPIO and IgG-USPIO, the latter as a control reagent, and determined concentrations according to the Fe content. Lung cancer A549 cells were cultured and immunocytochemistry (SP) was used to detect the expression of EGFR on cells. We detected the binding rate of C225-USPIO to A549 cells with immunofluorescence staining and flow cytometry. We cultured A549 cells with C225-USPIO at a Fe concentration of 50 µg/ml and assayed the binding of C225-USPIO after 1 hour with Prussian blue staining and transmission electron microscopy (TEM). We determined the effects on imaging of the contrast agent targeted to cells using a 4.7T MRI. We did scanning on the cells labeled with C225-USPIO, IgG-USPIO, and distilled water, respectively. The scanning sequences included axial T1WI, T2WI.

Results: Immunocytochemical detection of lung cancer A549 cells found them positive for EGFR expression. Immunofluorescence staining and flow cytometry after cultivation with different concentrations of C225-USPIO showed the binding rate higher than the control. Prussian blue staining and transmission electron microscopy revealed that in the C225-USPIO contrast agent group of cells the particle content of Fe in cytoplasmic vesicles or on surface was more than that in the control group. The 4.7T MR imaging (MRI) scan revealed the T2WI signal in the C225-USPIO group of cells decreased significantly more than in unlabeled cells, but there was no significant difference between the time gradients.

Conclusions: We successfully constructed the molecular imaging agent C225-USPIO targeting the EGFR of A549 lung cancer cells. The imaging agent showed good targeting effect and specificity, and reduced MRI T2 value significantly, thus such molecular contrast agents could provide a new way to measure EGFR levels.
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July 2012

[A case-control study on the risk factors of work-related acute pesticide poisoning among farmers from Jiangsu province].

Zhonghua Liu Xing Bing Xue Za Zhi 2012 Apr;33(4):382-5

Southeast University Injury Prevention Research Institute/School of Public Health, Southeast University, Nanjing 210009, China.

Objective: To explore the risk factors on cases regarding work-related acute pesticide poisoning among farmers of Jiangsu province.

Methods: A population-based, 1:2 matched case-control study was carried out, with 121 patients as case-group paired by 242 persons with same gender, district and age less then difference of 3 years, as controls. Cases were the ones who had suffered from work-related acute pesticide poisoning. A unified questionnaire was used. Data base was established by EpiData 3.1, and SPSS 16.0 was used for both data single factor and multi-conditional logistics regression analysis.

Results: Results from the single factor logistic regression analysis showed that the related risk factors were: lack of safety guidance, lack of readable labels before praying pesticides, no regression during application, using hand to wipe sweat, using leaking knapsack, body contaminated during application and continuing to work when feeling ill after the contact of pesticides. Results from multi-conditional logistic regression analysis indicated that the lack of safety guidance (OR=2.25, 95%CI: 1.35-3.74), no readable labels before praying pesticides (OR=1.95, 95%CI: 1.19-3.18), wiping the sweat by hand during application (OR=1.97, 95%CI: 1.20-3.24) and using leaking knapsack during application (OR=1.82, 95%CI:1.10-3.01) were risk factors for the occurrence of work-related acute pesticide poisoning.

Conclusion: The lack of safety guidance, no readable labels before praying pesticides, wiping the sweat by hand or using leaking knapsack during application were correlated to the occurrence of work-related acute pesticide poisoning.
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April 2012

Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation.

Acta Pharmacol Sin 2012 May 16;33(5):682-90. Epub 2012 Apr 16.

Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aim: To investigate the mechanisms underlying the anticancer effect of celecoxib on nasopharyngeal carcinoma (NPC).

Methods: NPC cell lines, HNE1 and CNE1-LMP1, were treated with various concentrations of celecoxib for 48 h. The antiproliferative effect of celecoxib was assessed using MTT assay. Both cell cycle profiles and apoptosis were analyzed using flow cytometry. Western blot was used to measure the levels of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3(Y705) (pSTAT3(Y705)), COX-2, Survivin, Mcl-1, Bcl-2 and Cyclin D1.

Results: Celecoxib (10-75 μmol/L) inhibited the proliferation of the NPC cell lines in a dose-dependent manner. Celecoxib (25 and 50 μmol/L) induced apoptosis and cell-cycle arrest at the G(0)/G(1) checkpoint in the NPC cell lines, which was associated with significantly reduced STAT3 phosphorylation. The genes downstream of STAT3 (ie, Survivin, Mcl-1, Bcl-2 and Cyclin D1) were significantly down-regulated after exposure to celecoxib (25 and 50 μmol/L).

Conclusion: The anticancer effects of celecoxib on NPC cell lines results from inducing apoptosis and cell cycle arrest, which may be partly mediated through the STAT3 pathway.
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http://dx.doi.org/10.1038/aps.2012.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010355PMC
May 2012

Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial.

Lancet Oncol 2012 Feb 7;13(2):163-71. Epub 2011 Dec 7.

State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, Guangzhou, China.

Background: The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone.

Methods: We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3-4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m(2) cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0-2·27 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60-66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m(2) adjuvant cisplatin and 800 mg/m(2) per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT00677118.

Findings: 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3-61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81-90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78-88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49-1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of 205 patients treated with adjuvant chemotherapy).

Interpretation: Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials.

Funding: Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010-178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010).
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http://dx.doi.org/10.1016/S1470-2045(11)70320-5DOI Listing
February 2012

[Application of Susceptible-Infected-Recovered model in dealing with an outbreak of acute hemorrhagic conjunctivitis on one school campus].

Zhonghua Liu Xing Bing Xue Za Zhi 2011 Aug;32(8):830-3

Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha 410078, China.

To simulate intervention measures in controlling an outbreak of acute hemorrhagic conjunctivitis on one school campus by using the Susceptible-Infected-Recovered (SIR) model, to provide evidence for preparedness and response to the epidemic. Classical SIR model was used to model the epidemic. Malthusian exponential decline method was employed to estimate the infective coefficient β for interventions. The initial value of parameters was determined based on empirical data. The modeling was implemented using Matlab 7.1 software. Without interventions, the outbreak was expected to experience three phrases: (1) early stage (the first 5 days) in which the epidemic developed slowly and could be intervened easily; (2) rapid growing stage (6 - 15 days) in which the number of infected cases increased quickly and the epidemic could not be well controlled; and (3) medium and late stage (16 days and later) in which more than 90% of the susceptible persons were infected but the intervention measures failed to prevent the epidemic. With the implementation of interventions, the epidemic was predicted to be controlled in the early stage, under the SIR model. The simulation based on the SIR model kept an acceptable consistency with the actual development of epidemic after the implementation of intervention measures. The SIR model seemed effective in modeling interventions to the epidemic of acute hemorrhagic conjunctivitis in the schools.
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August 2011

[An epidemiological survey on the incidence of non-fatal injury and influencing factors among children under 5 years old in China].

Zhonghua Liu Xing Bing Xue Za Zhi 2011 Aug;32(8):773-6

Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha 410078, China.

Objective: To determine the incidence of non-fatal injuries and related influencing factors among children under 5 years old in China.

Methods: Data involving 10 819 children under 5 years old was from the Fourth National Health Service Survey of China. Injury-related indicators include: history of ever having had an injury, its frequency, cause, location and severity of the injury. A two-level Poisson regression was used to examine the significance of related socio-economic variables.

Results: The overall incidence rate of nonfatal injuries among children under 5 years old was 16.0 per 1000 population in the prior 12 months. The first three leading causes of non-fatal injuries were falls, animal bite, fire/burn among children under 1 year old, with the rates as 3.9, 1.8 and 1.8 per 1000 population, respectively. For children aged 1 to 4 years old, the first three leading causes were animal bite, fall, fire/burn with rates as 6.5, 6.0 and 2.9 per 1000 population, respectively. 83.0% and 69.0% of last injuries occurred at home for the above said two age groups. No disability was found among children younger than 1 year old who suffered from a nonfatal injury while for the 1 - 4 age group, the disability accounted for 1.0% of injury-induced outcomes. After adjusting other variables, boys had 1.57 times the risk of injury compared with girls in the 1 - 4 age group (P < 0.05). The differences on the effects regarding ethnicity, per capita household income, and place were insignificant (P > 0.05). None of the socio-economic variables was found that significantly related to the non-fatal injury risk among children under 1 year old (P > 0.05).

Conclusion: The incidence of nonfatal injuries among children under 5 years old was 16.0 per 1000 population in the prior 12 months. The three leading causes of injuries were animal bite, falls, fire/burn respectively. Home was the most common place that non-fatal injuries occurred. Boys had a higher risk of injury compared with girls among children aged 1 to 4 years old and the difference was significant.
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August 2011

Identification and characterization of a novel fumarase gene by metagenome expression cloning from marine microorganisms.

Microb Cell Fact 2010 Nov 23;9:91. Epub 2010 Nov 23.

Guangxi Key Laboratory of Subtropical Bioresources Conservation and Utilization, College of Life Science and Technology, Guangxi University, 100 Daxue East Road, Nanning, Guangxi, 530004, People's Republic of China.

Background: Fumarase catalyzes the reversible hydration of fumarate to L-malate and is a key enzyme in the tricarboxylic acid (TCA) cycle and in amino acid metabolism. Fumarase is also used for the industrial production of L-malate from the substrate fumarate. Thermostable and high-activity fumarases from organisms that inhabit extreme environments may have great potential in industry, biotechnology, and basic research. The marine environment is highly complex and considered one of the main reservoirs of microbial diversity on the planet. However, most of the microorganisms are inaccessible in nature and are not easily cultivated in the laboratory. Metagenomic approaches provide a powerful tool to isolate and identify enzymes with novel biocatalytic activities for various biotechnological applications.

Results: A plasmid metagenomic library was constructed from uncultivated marine microorganisms within marine water samples. Through sequence-based screening of the DNA library, a gene encoding a novel fumarase (named FumF) was isolated. Amino acid sequence analysis revealed that the FumF protein shared the greatest homology with Class II fumarate hydratases from Bacteroides sp. 2_1_33B and Parabacteroides distasonis ATCC 8503 (26% identical and 43% similar). The putative fumarase gene was subcloned into pETBlue-2 vector and expressed in E. coli BL21(DE3)pLysS. The recombinant protein was purified to homogeneity. Functional characterization by high performance liquid chromatography confirmed that the recombinant FumF protein catalyzed the hydration of fumarate to form L-malate. The maximum activity for FumF protein occurred at pH 8.5 and 55°C in 5 mM Mg(2+). The enzyme showed higher affinity and catalytic efficiency under optimal reaction conditions: K(m) = 0.48 mM, V(max) = 827 μM/min/mg, and k(cat)/K(m) = 1900 mM/s.

Conclusions: We isolated a novel fumarase gene, fumF, from a sequence-based screen of a plasmid metagenomic library from uncultivated marine microorganisms. The properties of FumF protein may be ideal for the industrial production of L-malate under higher temperature conditions. The identification of FumF underscores the potential of marine metagenome screening for novel biomolecules.
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http://dx.doi.org/10.1186/1475-2859-9-91DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002918PMC
November 2010

[Development and testing of a preparedness and response capacity questionnaire in public health emergency for Chinese provincial and municipal governments].

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2008 Dec;33(12):1142-7

Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha 410078, China.

Objective: To develop a capacity questionnaire in public health emergency for Chinese local governments.

Methods: Literature reviews, conceptual modelling, stake-holder analysis, focus group, interview, and Delphi technique were employed together to develop the questionnaire. Classical test theory and case study were used to assess the reliability and validity.

Results: (1) A 2-dimension conceptual model was built. A preparedness and response capacity questionnaire in public health emergency with 10 dimensions and 204 items, was developed. (2) Reliability and validity results. Internal consistency: except for dimension 3 and 8, the Cronbach's alpha coefficient of other dimensions was higher than 0.60. The alpha coefficients of dimension 3 and dimension 8 were 0.59 and 0.39 respectively; Content validity: the questionnaire was recognized by the investigatees; Construct validity: the Spearman correlation coefficients among the 10 dimensions fluctuated around 0.50, ranging from 0.26 to 0.75 (P<0.05); Discrimination validity: comparisons of 10 dimensions among 4 provinces did not show statistical significance using One-way analysis of variance (P>0.05). Criterion-related validity: case study showed significant difference among the 10 dimensions in Beijing between February 2003 (before SARS event) and November 2005 (after SARS event).

Conclusion: The preparedness and response capacity questionnaire in public health emergency is a reliable and valid tool, which can be used in all provinces and municipalities in China.
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December 2008

[Assessment of capacity for logisty, public education, and training in public health emergency management in China].

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2008 Oct;33(10):947-51

Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha 410078, China.

Objective: To assess the capacity for logistics, public education, and training in managing public health emergency in China at present.

Methods: Four provinces were selected using stratified sampling. All the municipalities of these 4 provinces were assessed using the 9th and 10th subscales (logistics, public education and training) of Preparedness and response capacity questionnaire for public health emergencies for provincial or municipal governments developed by the Center for Health Statistics and Information, Ministry of Health of China.

Results: Sixty of the 66 questionnaires (90.91%) were collected. Among the 60 investigated municipalities, 80% established a specific agency to take charge of emergency material storage, management and allocation, 65% developed standard for material storage, 35% developed standard of places for material storage, 25% built regulation for testing, maintaining, and updating the emergency materials regularly, 45% arranged budget for routine payment, 27% established standard of emergency fund, and 28% set up the procedure to initiate emergency fund. The average of standard score of subscale 9 was 43.33 (95% confidence interval, 35.65~51.01). 25% of the 60 municipalities conducted assessment for training in the past 2 years, 53% developed plan for emergency personnel training, 20% developed effectiveness assessment regulation of emergency personnel training, 80% assigned a specific agency to be responsible for public education, and 23% established regulation for public education. The average of standard score of subscale 10 was 47.43 (95% confidence interval, 40.69~54.17).

Conclusion: Serious problems are found in logistics, public education, and training for public health emergency management in China. Measures should be taken immediately by the central and local government to improve these capacities.
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October 2008

[Brief self-administered risk questionnaire for common nutrition-related diseases in middle school students].

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2008 Mar;33(3):204-9

Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha 410078, China.

Objective: To develop a self-administered risk questionnaire for common nutrition-related diseases in middle school students.

Methods: Two phases were conducted to develop the questionnaire: scale development and validation. Phase 1 included 7 steps: (1) determining the objective, theoretical framework, principles and format for indicator generation; (2) setting up the preliminary indicator pool; (3) selecting indicators and forming pilot questionnaire through focus groups; (4) testing the pilot questionnaire; (5) further correcting the questionnaire using expert consultation; (6) choosing indicators again using good-poor analysis; and (7) shaping the final questionnaire. Phase 2 consisted of: (1) using the Pearson correlation coefficient to assess test-retest reliability; (2) using the Cronbach's alpha coefficient to assess the internal consistency reliability; (3) using the feedback from field investigation to assess face validity; and (4) using explanatory factor analysis to assess construct validity. Students from 96 classes were selected at random in Hunan Province as the field test samples using stratified sampling and cluster sampling. And the students from 4 out of the 96 classes were chosen again to serve as the test-retest samples. We used Epidata 3.0 to build the database and SPSS 11.0 to analyze the data.

Results: A brief self-administered risk questionnaire for common nutrition-related diseases in middle school students with 12 items being formed after Phase 1. Good-poor analysis showed results from t tests for each item were statistically significant (P<0.05). The Pearson correlation coefficient was 0.76 (P<0.05) and the Cronbach's alpha coefficient was 0.56. The questionnaire was accepted by the students participating in the field test. Four common factors were extracted using explanatory factor analysis, accounting for 50.18% of the total variation.

Conclusion: The brief self-administered risk questionnaire for common nutrition-related diseases in middle school students is reliable and valid.
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March 2008