Objective： To explore an ideal approach for detecting the physical status of HPV-16 in clinic use and to investigate the integrated HPV-16 in CINs and cervical cancer. Methods： Multiplex real-time PCR method was est...Objective： To explore an ideal approach for detecting the physical status of HPV-16 in clinic use and to investigate the integrated HPV-16 in CINs and cervical cancer. Methods： Multiplex real-time PCR method was established to quantify the copy numbers of E2 and E6 genes （E2/E6） for analysis of the physical status of HPV-16 DNA and this assay was compared to Southern blot analysis. HPV-16-containing paraffin-embedded tissues including 49 CINs and 51 cervical squamous cancers were detected using the method. Results： （1） The cutoff ratio of E2/E6 to distinguish pure episomal from mixed HPV-16, was 0.81 in the multiplex real-time PCR; （2） The agreement rate between multiplex real-time PCR and Southern blot was 81.5% （the Kappa statistic was 0.844, P〈0.001）; （3） HPV-16 DNA existed in an episomal form in 57.1% and mixed form in 42.9% of CIN I lesions; The concomitant form of HPV-16 （〉70%） constituted the majodty in CIN Ⅱ and CIN Ⅲ; HPV-16 DNA mostly integrated into the host chromosome （s） in squamous cervical cancers （68.6%）; （4） The incidence of HPV-16 integration was increased with the degree of cervical lesions; （5） The frequency of pure integrated HPV-16 in stage Ⅱ＋Ⅲ （88%） was significantly higher than that in stage Ⅰ （33.3%）. Conclusion： （1） Mutiplex real-time PCR provides a rapid, sensitive and reliable method for clinic detection of the physical state of HPV-16 DNA; （2） The integration of the HPV-16 DNA is a very eady and important event in the progression from preinvasive to invasive cervical cancer; （3） The pure integrated status of HPV-16 in cervical cancer may be associated with poor prognosis of cervical cancer, but further study will be needed to prove its prognostic significance.展开更多
OBJECTIVE To determine the association between viral loadof human papillomavirus 16 (HPV16) DNA in the primary focusof cervical carcinoma and HPV16 DNA in pelvic lymph nodes.METHODS The HPV16 DNA load was measured by ...OBJECTIVE To determine the association between viral loadof human papillomavirus 16 (HPV16) DNA in the primary focusof cervical carcinoma and HPV16 DNA in pelvic lymph nodes.METHODS The HPV16 DNA load was measured by fluorescentquantitation polymerase chain reaction (FQ-PCR) in 17 primaryfoci. HPV16 DNA was detected by polymerase chain reaction(PCR) using HPV16 type-specific primers in 296 pelvic lymphnodes which were from 17 cases of cervical cancer.RESULTS The viral load of HPV16 DNA showed statisticallysignificant differences between tumors with a diameter of < 4cm and ≥ 4 cm (P < 0.05). Seven of 17 cervical cancer cases hadHPV16 DNA positive lymph nodes, designated as the positivegroup, while the remaining 10 without positive lymph nodes wasdesignated the negative group. The average load of HPV16 DNAshowed no significant difference between the 2 groups (P > 0.05).The load of HPV16 in the primary lesion was not associated withthat in the lymph nodes. There were 38 HPV16 DNA positivenodes in the total 296 nodes. The rate of positivity of HPV16 DNAin lymph nodes showed statistically significant differences inconsideration of maximum tumor diameter, tumor differentiation,histologic type, depth of myometial infiltration and the metastaticstatus of the nodes, respectively (P < 0.05).CONCLUSION Viral load of HPV16 in the primary cancer focuscorrelated with the quantity of tumor cells in the primary focusbut not with the existence of HPV DNA positive lymph nodes.Detection of HPV DNA may help to find the early metastases thatcannot be evaluated histopathologically, but the prognostic valueof HPV positive lymph nodes needs further examination.展开更多
Objective In kinesin-3,the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A.The functio...Objective In kinesin-3,the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A.The function of this neck hinge for controlling processive movement,however,remains unclear.Methods We made a series of modifications to the neck hinges of KIF13B and KIF1A and tested their movement using a single-molecule motility assay.Results In KIF13B,the insertion of flexible residues before or after the proline differentially impacts the processivity or velocity,while the removal of this proline increases the both.In KIF1A,the deletion of entire flexible neck hinge merely enhances the processivity.The engineering of these hinge-truncated necks of kinesin-3 into kinesin-1 similarly boosts the processive movement of kinesin-1.Conclusion The neck hinge in kinesin-3 controls its processive movement and proper modifications tune the motor motility,which provides a novel strategy to reshape the processive movement of kinesin motors.展开更多
Objective： To assess the influence of different hinge positions on clinical results of expansive open-door laminoplasty （EOLP） for cervical spondylotic myelopathy （CSM）.Methods： A total of 102 CSM patients who u...Objective： To assess the influence of different hinge positions on clinical results of expansive open-door laminoplasty （EOLP） for cervical spondylotic myelopathy （CSM）.Methods： A total of 102 CSM patients who underwent EOLP from February 2006 to February 2007 were enrolled in this randomized controlled trial. Using a random digits table,57 patients with the hinge located at the inner margin of the lateral mass were classified as wide-open group, while 45 patients with the hinge positioned at the lamina margin served as narrow-open group. All patients were observed over 24 months, and the clinical and radiological results were analyzed statistically.Results： There were no significant differences in operation duration, intraoperative bleeding volume, Japanese Orthopaedic Association （JOA） scores, cervical curvature index, range of motion and neural function recovery rate.The neural functions were satisfactorily improved after surgery in both groups, while the severity of axial symptoms was significantly lower in the narrow-open group than in the wide-open group （P=0.003）. The incidence of C5 palsy in the wide-open group was higher than that in the narrowopen group （5.3% vs 0）, even though the difference did not reach statistical significance （one tailed Fisher＇s exact test,P=0.17）.Conclusions： Proper inward shift of the hinge can ensure effectiveness of surgical decompression, avoid an excessive backward shift of the spinal cord, decrease the incidence of C5 palsy and alleviate the severity of axial symptoms.展开更多
Objective： In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma （HNSCC）-associated long noncoding RNAs （IncRNAs）, and to discover potential IncRNA prognostic biomarkers for...Objective： In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma （HNSCC）-associated long noncoding RNAs （IncRNAs）, and to discover potential IncRNA prognostic biomarkers for HNSCC based on next-generation RNA-seq. Methods： RNA-seq data of 546 samples from patients with HNSCC were downloaded from The Cancer Genome Atlas （TCGA）, including 43 paired samples of tumor tissue and adjacent normal tissue. An integrated analysis incorporating differential expression, weighted gene co-expression networks, functional enrichment, clinical parameters, and survival analysis was conducted to discover HNSCC-associated IncRNAs. The function of CYTOR was verified by cell-based experiments. To further identify IncRNAs with prognostic significance, a multivariate Cox proportional hazard regression analysis was performed. The identified IncRNAs were validated with an independent cohort using clinical feature relevance analysis and multivariate Cox regression analysis. Results： We identified nine HNSCC-relevant IncRNAs likely to play pivotal roles in HNSCC onset and development. By functional enrichment analysis, we revealed that CYTOR might participate in the multistep pathological processes of cancer, such as ribosome biogenesis and maintenance of genomic stability. CY-I-OR was identified to be positively correlated with lymph node metastasis, and significantly negatively correlated with overall survival （OS） and disease free survival （DFS） of HNSCC patients. Moreover, CYTOR inhibited cell apoptosis following treatment with the chemotherapeutic drug diamminedichloroplatinum （DDP）. HCG22, the most dramatically down-regulated IncRNA in tumor tissue, may function in epidermis differentiation. It was also significantly associated with several clinical features of patients with HNSCC, and positively correlated with patient survival. CYTOR and HCG22 maintained their prognostic values in- dependent of several clinical features in multivariate Cox hazards analysis. Notably, validation either based on an independent HNSCC cohort or by laboratory experiments confirmed these findings. Conclusions： Our transcriptomic analysis suggested that dysregulation of these HNSCC-associated IncRNAs might be involved in HNSCC oncogenesis and progression. Moreover, CYTOR and HCG22 were confirmed as two independent prognostic factors for HNSCC patient survival, providing new insights into the roles of these IncRNAs in HNSCC as well as clinical applications.展开更多
We first recall some basic facts from the theory of discrete-time Markov chains arising from two types neutral and non-neutral evolution models of population genetics with constant size. We then define and analyze a v...We first recall some basic facts from the theory of discrete-time Markov chains arising from two types neutral and non-neutral evolution models of population genetics with constant size. We then define and analyze a version of such models whose fluctuating total population size is conserved on average only. In our model, the population of interest is seen as being embedded in a frame process which is a critical Galton Watson process. In this context, we address problems such as extinction, fixation, size of the population at fixation and survival probability to a bottleneck effect of the environment.展开更多
基金Supported by postdoctoral research fellowship from FIGO/ESRF (International Federation of Gynecology and Obsterics/Ernst Schering Research Foundation).
文摘Objective： To explore an ideal approach for detecting the physical status of HPV-16 in clinic use and to investigate the integrated HPV-16 in CINs and cervical cancer. Methods： Multiplex real-time PCR method was established to quantify the copy numbers of E2 and E6 genes （E2/E6） for analysis of the physical status of HPV-16 DNA and this assay was compared to Southern blot analysis. HPV-16-containing paraffin-embedded tissues including 49 CINs and 51 cervical squamous cancers were detected using the method. Results： （1） The cutoff ratio of E2/E6 to distinguish pure episomal from mixed HPV-16, was 0.81 in the multiplex real-time PCR; （2） The agreement rate between multiplex real-time PCR and Southern blot was 81.5% （the Kappa statistic was 0.844, P〈0.001）; （3） HPV-16 DNA existed in an episomal form in 57.1% and mixed form in 42.9% of CIN I lesions; The concomitant form of HPV-16 （〉70%） constituted the majodty in CIN Ⅱ and CIN Ⅲ; HPV-16 DNA mostly integrated into the host chromosome （s） in squamous cervical cancers （68.6%）; （4） The incidence of HPV-16 integration was increased with the degree of cervical lesions; （5） The frequency of pure integrated HPV-16 in stage Ⅱ＋Ⅲ （88%） was significantly higher than that in stage Ⅰ （33.3%）. Conclusion： （1） Mutiplex real-time PCR provides a rapid, sensitive and reliable method for clinic detection of the physical state of HPV-16 DNA; （2） The integration of the HPV-16 DNA is a very eady and important event in the progression from preinvasive to invasive cervical cancer; （3） The pure integrated status of HPV-16 in cervical cancer may be associated with poor prognosis of cervical cancer, but further study will be needed to prove its prognostic significance.
文摘OBJECTIVE To determine the association between viral loadof human papillomavirus 16 (HPV16) DNA in the primary focusof cervical carcinoma and HPV16 DNA in pelvic lymph nodes.METHODS The HPV16 DNA load was measured by fluorescentquantitation polymerase chain reaction (FQ-PCR) in 17 primaryfoci. HPV16 DNA was detected by polymerase chain reaction(PCR) using HPV16 type-specific primers in 296 pelvic lymphnodes which were from 17 cases of cervical cancer.RESULTS The viral load of HPV16 DNA showed statisticallysignificant differences between tumors with a diameter of < 4cm and ≥ 4 cm (P < 0.05). Seven of 17 cervical cancer cases hadHPV16 DNA positive lymph nodes, designated as the positivegroup, while the remaining 10 without positive lymph nodes wasdesignated the negative group. The average load of HPV16 DNAshowed no significant difference between the 2 groups (P > 0.05).The load of HPV16 in the primary lesion was not associated withthat in the lymph nodes. There were 38 HPV16 DNA positivenodes in the total 296 nodes. The rate of positivity of HPV16 DNAin lymph nodes showed statistically significant differences inconsideration of maximum tumor diameter, tumor differentiation,histologic type, depth of myometial infiltration and the metastaticstatus of the nodes, respectively (P < 0.05).CONCLUSION Viral load of HPV16 in the primary cancer focuscorrelated with the quantity of tumor cells in the primary focusbut not with the existence of HPV DNA positive lymph nodes.Detection of HPV DNA may help to find the early metastases thatcannot be evaluated histopathologically, but the prognostic valueof HPV positive lymph nodes needs further examination.
文摘Objective In kinesin-3,the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A.The function of this neck hinge for controlling processive movement,however,remains unclear.Methods We made a series of modifications to the neck hinges of KIF13B and KIF1A and tested their movement using a single-molecule motility assay.Results In KIF13B,the insertion of flexible residues before or after the proline differentially impacts the processivity or velocity,while the removal of this proline increases the both.In KIF1A,the deletion of entire flexible neck hinge merely enhances the processivity.The engineering of these hinge-truncated necks of kinesin-3 into kinesin-1 similarly boosts the processive movement of kinesin-1.Conclusion The neck hinge in kinesin-3 controls its processive movement and proper modifications tune the motor motility,which provides a novel strategy to reshape the processive movement of kinesin motors.
文摘Objective： To assess the influence of different hinge positions on clinical results of expansive open-door laminoplasty （EOLP） for cervical spondylotic myelopathy （CSM）.Methods： A total of 102 CSM patients who underwent EOLP from February 2006 to February 2007 were enrolled in this randomized controlled trial. Using a random digits table,57 patients with the hinge located at the inner margin of the lateral mass were classified as wide-open group, while 45 patients with the hinge positioned at the lamina margin served as narrow-open group. All patients were observed over 24 months, and the clinical and radiological results were analyzed statistically.Results： There were no significant differences in operation duration, intraoperative bleeding volume, Japanese Orthopaedic Association （JOA） scores, cervical curvature index, range of motion and neural function recovery rate.The neural functions were satisfactorily improved after surgery in both groups, while the severity of axial symptoms was significantly lower in the narrow-open group than in the wide-open group （P=0.003）. The incidence of C5 palsy in the wide-open group was higher than that in the narrowopen group （5.3% vs 0）, even though the difference did not reach statistical significance （one tailed Fisher＇s exact test,P=0.17）.Conclusions： Proper inward shift of the hinge can ensure effectiveness of surgical decompression, avoid an excessive backward shift of the spinal cord, decrease the incidence of C5 palsy and alleviate the severity of axial symptoms.
基金Project supported by the National Natural Science Foundation of China(Nos.31471226 and 91440108)the Fundamental Research Funds for the Central Universities(Nos.WK2070000044 and WK2070000034),China
文摘Objective： In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma （HNSCC）-associated long noncoding RNAs （IncRNAs）, and to discover potential IncRNA prognostic biomarkers for HNSCC based on next-generation RNA-seq. Methods： RNA-seq data of 546 samples from patients with HNSCC were downloaded from The Cancer Genome Atlas （TCGA）, including 43 paired samples of tumor tissue and adjacent normal tissue. An integrated analysis incorporating differential expression, weighted gene co-expression networks, functional enrichment, clinical parameters, and survival analysis was conducted to discover HNSCC-associated IncRNAs. The function of CYTOR was verified by cell-based experiments. To further identify IncRNAs with prognostic significance, a multivariate Cox proportional hazard regression analysis was performed. The identified IncRNAs were validated with an independent cohort using clinical feature relevance analysis and multivariate Cox regression analysis. Results： We identified nine HNSCC-relevant IncRNAs likely to play pivotal roles in HNSCC onset and development. By functional enrichment analysis, we revealed that CYTOR might participate in the multistep pathological processes of cancer, such as ribosome biogenesis and maintenance of genomic stability. CY-I-OR was identified to be positively correlated with lymph node metastasis, and significantly negatively correlated with overall survival （OS） and disease free survival （DFS） of HNSCC patients. Moreover, CYTOR inhibited cell apoptosis following treatment with the chemotherapeutic drug diamminedichloroplatinum （DDP）. HCG22, the most dramatically down-regulated IncRNA in tumor tissue, may function in epidermis differentiation. It was also significantly associated with several clinical features of patients with HNSCC, and positively correlated with patient survival. CYTOR and HCG22 maintained their prognostic values in- dependent of several clinical features in multivariate Cox hazards analysis. Notably, validation either based on an independent HNSCC cohort or by laboratory experiments confirmed these findings. Conclusions： Our transcriptomic analysis suggested that dysregulation of these HNSCC-associated IncRNAs might be involved in HNSCC oncogenesis and progression. Moreover, CYTOR and HCG22 were confirmed as two independent prognostic factors for HNSCC patient survival, providing new insights into the roles of these IncRNAs in HNSCC as well as clinical applications.
文摘We first recall some basic facts from the theory of discrete-time Markov chains arising from two types neutral and non-neutral evolution models of population genetics with constant size. We then define and analyze a version of such models whose fluctuating total population size is conserved on average only. In our model, the population of interest is seen as being embedded in a frame process which is a critical Galton Watson process. In this context, we address problems such as extinction, fixation, size of the population at fixation and survival probability to a bottleneck effect of the environment.
