In this paper,the soil-pile system of O-cell test of pile is simplified as an axi-symmetric problem.By using aggregation of quadrilateral isoparametric elements to simulate pile and soil,setting Goodman's elements...In this paper,the soil-pile system of O-cell test of pile is simplified as an axi-symmetric problem.By using aggregation of quadrilateral isoparametric elements to simulate pile and soil,setting Goodman's elements between pile and soils,a method of numerical simulation analysis on O-cell test of pile is presented with the consideration of nonlinear mechanical behavior of soils and pile-soil interface.The method is applied to the analysis of a case of O-cell test of pile.The load-displacement curves and axial force curves of upper pile and lower pile obtained from the O-cell test of pile are fitted,and parameters of the mechanical model of soils and interface are determined.Analysis results validate that the numerical simulation analysis method put forward in this paper is applicable.Furthermore,the interaction and influence of upper pile and lower pile in the O-cell test are also studied with the method.The result shows that if load box is located in a soil layer with fine mechanical behavior,the interaction of upper pile and lower pile in O-cell test can be ignored generally.展开更多
Background: Chemotherapy is a mainstay of tumor therapy, however, it is predominantly applied according to empirically developed recommendations derived from statistical relapse rates occurring years after the treatme...Background: Chemotherapy is a mainstay of tumor therapy, however, it is predominantly applied according to empirically developed recommendations derived from statistical relapse rates occurring years after the treatment in the adjuvant situation and from progression-free interval data in the metastatic situation, without any possibility of individually determining the efficacy in the adjuvant situation and with loss of time and quality of life in the metastatic situation if the drugs chosen are not effective. Here, we present a method to determine the efficiency of chemotherapeutic drugs using tumor cells circulating in blood as the part of the tumor actually available in the patient’s body for chemosensitivity testing. Methodology/Principal Findings: After only red blood cell lysis, omitting any enrichment (analogous to other blood cell enumeration methods, including rare CD34 cells), the white cells comprising the circulating epithelial tumor cells (CETC) are exposed to the drugs in question in different concentrations and for different periods of time. Staining with a fluorescence-labeled anti-epithelial antibody detects both vital and dying tumor cells, distinguishing vital from dying cells through membrane permeability and nuclear staining with propidium iodide. Increasing percentages of dying tumor cells are observed dependent on time and concentration. The sensitivity can vary during therapy and was correlated with decrease or increase in CETC and clinical outcome. Conclusions/Significance: Thus, we are able to show that chemosensitivity testing of circulating tumor cells provides real-time information about the sensitivity of the tumor present in the patient, even at different times during therapy, and correlates with treatment success.展开更多
Introduction: Over the past few years, molecular targeted therapies have been?emerging for the treatment of metastatic non-small cell lung cancer (NSCLC).?Targeted therapy is associated with improved outcomes in patie...Introduction: Over the past few years, molecular targeted therapies have been?emerging for the treatment of metastatic non-small cell lung cancer (NSCLC).?Targeted therapy is associated with improved outcomes in patients with identified gene alterations, and national guidelines recommend routine biomarker testing. This study evaluated real-world rates of documented epidermal growth factor receptor (EGFR) mutation and other biomarker testing in patients with advanced NSCLC over time.?Methods: Adult patients with Stage IV NSCLC were identified between January 1, 2012 and May 31, 2017 from the US Oncology Network iKnowMedTM?electronic health records. Patients were examined overall and by histology. Rates of documented EGFR mutation and other biomarker testing were calculated. Multivariable regression analyses were conducted to identify characteristics associated with documented biomarker testing. Results: A total of 14,461 patients were identified: median age was 69.3 years, 52.3% were male, 14.6% were nonsmokers, and 64.7% had non-squamous histology.?EGFR mutation testing rates were 35.5%?overall, with an increase in rates seen over time: 30.0% in 2012 to 44.0% in 2016?(p??0.001).?Anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and programmed death-ligand 1 (PD-L1) mutation testing rates were 32.9%, 5.7%, and 5.7%, respectively. More recent diagnosis year, non-squamous histology, larger practice size, and nonsmoking status were strongly associated with higher documented EGFR and ALK mutation testing rates.?Conclusions: EGFR mutation testing rates steadily increased over time, but remained less than 50%, with lower mutation testing rates reported for ALK, ROS1, and PD-L1, suggesting that opportunities exist to improve education on testing for biomarkers in NSCLC.展开更多
Objective To test Calcium ion(Ca2+) flow at the head and end of outer hair cells(OHCs) in resting state and in response to Nimodipine treatment.Methods Non-invasive micro-test techniques were used to study Ca2+ in iso...Objective To test Calcium ion(Ca2+) flow at the head and end of outer hair cells(OHCs) in resting state and in response to Nimodipine treatment.Methods Non-invasive micro-test techniques were used to study Ca2+ in isolated OHCs in adult guinea pigs.Results Four types of Ca2+ transport were identified in OHCs on basilar membrane tissue fragments:influx at the head of with efflux at the bottom(type 1):efflux at the head of OHCs with influx at the bottom(type 2);influx at the both head and bottom(type 3);and efflux at the both head and bottom(type 4).However,only type 1 and type 3 of Ca2+ ion transport were detected in the cochlea.We propose that Ca2+ ion transport exists in adult guinea pig cochlear OHCs in resting state and is variable.Ca2 + flow in OHC can be inhibited by Nimodipine in resting state.展开更多
Objective To find a sensitive cytotoxic response to reflect the bio-toxicity of trace organic pollutants, the sensitivity and reliability of morphological change and proliferation inhibition of Vero cells exposed to 2...Objective To find a sensitive cytotoxic response to reflect the bio-toxicity of trace organic pollutants, the sensitivity and reliability of morphological change and proliferation inhibition of Vero cells exposed to 2, 4, 6-trichlorophenol （TCP） and the leachate from products related to drinking water （PRDW） were compared, and the mechanism of the morphological change in Vero cells exposed to chemical pollutants was studied. Methods Vero cells were treated by different concentration of TCP and the leachate from PRDW. Methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide （MTT） assay was carried out for proliferation inhibition. Bioluminescence method was carried out as another method to test the toxicity of TCP. Flow Cytometry assay was used to test cell Apoptosis and damage of cell-membrane. Results 0.25 mg/L TCP had an effect on cell morphology, and the proportion of morphologically changed cells increased with increasing TCP concentration. At low TCP concentrations, inhibition of cell proliferation did not seem to correlate to TCP concentration, and was negative when TCP concentration was 〈1.0 mg/L. After exposure to leachate from PRDW extracted at different temperatures, the percentage of morphologically changed cells increased with extracting temperature, but the inhibition of cell proliferation failed to reflect the correlation between extracting temperature and proliferation inhibition of Vero cells. Although the Sensitivity of bioluminescence method seems to be similar to morphological change in Veto cells, the bacterial in this method is not homologous enough with human body cells to reflect the toxicity to human body. These imply cell morphological change is a more sensitive and reliable method to reflect bio-toxicity of organic pollutants than proliferation inhibition. Flow cytometry analysis and cell rejuvenation experiments indicated cell membrane damage, which results in cell morphological change, was an early and sensitive cytotoxic response comparing with necrosis. Conelusion These results indicated that the cell membrane toxicity represented by morphological changes is a more sensitive and reliable method to indicate the composite bio-toxicity of trace chemicals than proliferation inhibition, inhibition on bioluminescence and necrosis. Nevertheless, the quantification of morphological change should be studied further.展开更多
目的探讨人绒毛膜促性腺激素(human chorionic gonadotrophin,hCG)激发试验在诊断不同分型性发育异常(disorder of sexual development,DSD)患儿中的价值。方法回顾性分析132例DSD患儿,按染色体核型分为46,XX组(n=10)、46,XY组(n=87)、...目的探讨人绒毛膜促性腺激素(human chorionic gonadotrophin,hCG)激发试验在诊断不同分型性发育异常(disorder of sexual development,DSD)患儿中的价值。方法回顾性分析132例DSD患儿,按染色体核型分为46,XX组(n=10)、46,XY组(n=87)、性染色体异常组(n=35),比较各组患儿hCG激发试验前后的性激素水平,分析形态学上是否存在睾丸组织对hCG激发试验结果的影响。结果3组患儿激发试验后睾酮(testosterone,T)增加倍数比较差异无统计学意义(P>0.05)。46,XY组中,5α-还原酶2缺乏症患儿激发试验后的T与双氢睾酮(dihydrotestosterone,DHT)比值高于其他46,XY DSD患儿(P<0.05)。形态学上,有睾丸组织的DSD患儿激发试验后T增加倍数高于无睾丸组织患儿(P<0.05)。结论hCG激发试验对于评估不同类型的DSD患儿的睾丸间质细胞存在和功能均具有重要价值,对于性腺性质不明确的DSD患儿,均建议行hCG激发试验。展开更多
We retrospectively assessed long-term pulmonary function in adults surviving for ≥5 years after myeloablative allogeneic hematopoietic stem cell transplantation and identified risk factors for late-onset noninfectiou...We retrospectively assessed long-term pulmonary function in adults surviving for ≥5 years after myeloablative allogeneic hematopoietic stem cell transplantation and identified risk factors for late-onset noninfectious pulmonary complications. Among 174 patients undergoing transplantation for hematologic malignancies between May 1994 and December 2004, 81 long-term survivors were evaluated. Pulmonary function tests (PFTs) were performed before conditioning, 3 months and 1 year after transplantation, and then annually. Eight patients (10%) had abnormal pulmonary function before transplantation, but this was not associated with late changes in PFTs. Patients with chronic graft-versus-host disease (GVHD) showed a significant decline of lung function after 3 years when compared with patients without chronic GVHD. Abnormal pretransplantation lung function was associated with pulmonary chronic GVHD according to National Institutes of Health criteria (score 0, n = 58;score 1, n = 14;score 2, n = 6;score 3, n = 3). Five patients with late-onset noninfectious pulmonary complications showed a decline of lung function at 1 year after transplantation. Only chronic GVHD was significantly related to late-onset noninfectious pulmonary complications. In conclusion, abnormal lung function before transplantation may be associated with a decline in pulmonary function within 1 year after transplantation, but late-onset noninfectious pulmonary complications could not be predicted from pretransplantation lung function.展开更多
文摘In this paper,the soil-pile system of O-cell test of pile is simplified as an axi-symmetric problem.By using aggregation of quadrilateral isoparametric elements to simulate pile and soil,setting Goodman's elements between pile and soils,a method of numerical simulation analysis on O-cell test of pile is presented with the consideration of nonlinear mechanical behavior of soils and pile-soil interface.The method is applied to the analysis of a case of O-cell test of pile.The load-displacement curves and axial force curves of upper pile and lower pile obtained from the O-cell test of pile are fitted,and parameters of the mechanical model of soils and interface are determined.Analysis results validate that the numerical simulation analysis method put forward in this paper is applicable.Furthermore,the interaction and influence of upper pile and lower pile in the O-cell test are also studied with the method.The result shows that if load box is located in a soil layer with fine mechanical behavior,the interaction of upper pile and lower pile in O-cell test can be ignored generally.
文摘Background: Chemotherapy is a mainstay of tumor therapy, however, it is predominantly applied according to empirically developed recommendations derived from statistical relapse rates occurring years after the treatment in the adjuvant situation and from progression-free interval data in the metastatic situation, without any possibility of individually determining the efficacy in the adjuvant situation and with loss of time and quality of life in the metastatic situation if the drugs chosen are not effective. Here, we present a method to determine the efficiency of chemotherapeutic drugs using tumor cells circulating in blood as the part of the tumor actually available in the patient’s body for chemosensitivity testing. Methodology/Principal Findings: After only red blood cell lysis, omitting any enrichment (analogous to other blood cell enumeration methods, including rare CD34 cells), the white cells comprising the circulating epithelial tumor cells (CETC) are exposed to the drugs in question in different concentrations and for different periods of time. Staining with a fluorescence-labeled anti-epithelial antibody detects both vital and dying tumor cells, distinguishing vital from dying cells through membrane permeability and nuclear staining with propidium iodide. Increasing percentages of dying tumor cells are observed dependent on time and concentration. The sensitivity can vary during therapy and was correlated with decrease or increase in CETC and clinical outcome. Conclusions/Significance: Thus, we are able to show that chemosensitivity testing of circulating tumor cells provides real-time information about the sensitivity of the tumor present in the patient, even at different times during therapy, and correlates with treatment success.
文摘Introduction: Over the past few years, molecular targeted therapies have been?emerging for the treatment of metastatic non-small cell lung cancer (NSCLC).?Targeted therapy is associated with improved outcomes in patients with identified gene alterations, and national guidelines recommend routine biomarker testing. This study evaluated real-world rates of documented epidermal growth factor receptor (EGFR) mutation and other biomarker testing in patients with advanced NSCLC over time.?Methods: Adult patients with Stage IV NSCLC were identified between January 1, 2012 and May 31, 2017 from the US Oncology Network iKnowMedTM?electronic health records. Patients were examined overall and by histology. Rates of documented EGFR mutation and other biomarker testing were calculated. Multivariable regression analyses were conducted to identify characteristics associated with documented biomarker testing. Results: A total of 14,461 patients were identified: median age was 69.3 years, 52.3% were male, 14.6% were nonsmokers, and 64.7% had non-squamous histology.?EGFR mutation testing rates were 35.5%?overall, with an increase in rates seen over time: 30.0% in 2012 to 44.0% in 2016?(p??0.001).?Anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and programmed death-ligand 1 (PD-L1) mutation testing rates were 32.9%, 5.7%, and 5.7%, respectively. More recent diagnosis year, non-squamous histology, larger practice size, and nonsmoking status were strongly associated with higher documented EGFR and ALK mutation testing rates.?Conclusions: EGFR mutation testing rates steadily increased over time, but remained less than 50%, with lower mutation testing rates reported for ALK, ROS1, and PD-L1, suggesting that opportunities exist to improve education on testing for biomarkers in NSCLC.
文摘Objective To test Calcium ion(Ca2+) flow at the head and end of outer hair cells(OHCs) in resting state and in response to Nimodipine treatment.Methods Non-invasive micro-test techniques were used to study Ca2+ in isolated OHCs in adult guinea pigs.Results Four types of Ca2+ transport were identified in OHCs on basilar membrane tissue fragments:influx at the head of with efflux at the bottom(type 1):efflux at the head of OHCs with influx at the bottom(type 2);influx at the both head and bottom(type 3);and efflux at the both head and bottom(type 4).However,only type 1 and type 3 of Ca2+ ion transport were detected in the cochlea.We propose that Ca2+ ion transport exists in adult guinea pig cochlear OHCs in resting state and is variable.Ca2 + flow in OHC can be inhibited by Nimodipine in resting state.
基金supported by the National Natural Science Foundation in China(No.20677043 and 40871217).
文摘Objective To find a sensitive cytotoxic response to reflect the bio-toxicity of trace organic pollutants, the sensitivity and reliability of morphological change and proliferation inhibition of Vero cells exposed to 2, 4, 6-trichlorophenol （TCP） and the leachate from products related to drinking water （PRDW） were compared, and the mechanism of the morphological change in Vero cells exposed to chemical pollutants was studied. Methods Vero cells were treated by different concentration of TCP and the leachate from PRDW. Methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide （MTT） assay was carried out for proliferation inhibition. Bioluminescence method was carried out as another method to test the toxicity of TCP. Flow Cytometry assay was used to test cell Apoptosis and damage of cell-membrane. Results 0.25 mg/L TCP had an effect on cell morphology, and the proportion of morphologically changed cells increased with increasing TCP concentration. At low TCP concentrations, inhibition of cell proliferation did not seem to correlate to TCP concentration, and was negative when TCP concentration was 〈1.0 mg/L. After exposure to leachate from PRDW extracted at different temperatures, the percentage of morphologically changed cells increased with extracting temperature, but the inhibition of cell proliferation failed to reflect the correlation between extracting temperature and proliferation inhibition of Vero cells. Although the Sensitivity of bioluminescence method seems to be similar to morphological change in Veto cells, the bacterial in this method is not homologous enough with human body cells to reflect the toxicity to human body. These imply cell morphological change is a more sensitive and reliable method to reflect bio-toxicity of organic pollutants than proliferation inhibition. Flow cytometry analysis and cell rejuvenation experiments indicated cell membrane damage, which results in cell morphological change, was an early and sensitive cytotoxic response comparing with necrosis. Conelusion These results indicated that the cell membrane toxicity represented by morphological changes is a more sensitive and reliable method to indicate the composite bio-toxicity of trace chemicals than proliferation inhibition, inhibition on bioluminescence and necrosis. Nevertheless, the quantification of morphological change should be studied further.
文摘目的探讨人绒毛膜促性腺激素(human chorionic gonadotrophin,hCG)激发试验在诊断不同分型性发育异常(disorder of sexual development,DSD)患儿中的价值。方法回顾性分析132例DSD患儿,按染色体核型分为46,XX组(n=10)、46,XY组(n=87)、性染色体异常组(n=35),比较各组患儿hCG激发试验前后的性激素水平,分析形态学上是否存在睾丸组织对hCG激发试验结果的影响。结果3组患儿激发试验后睾酮(testosterone,T)增加倍数比较差异无统计学意义(P>0.05)。46,XY组中,5α-还原酶2缺乏症患儿激发试验后的T与双氢睾酮(dihydrotestosterone,DHT)比值高于其他46,XY DSD患儿(P<0.05)。形态学上,有睾丸组织的DSD患儿激发试验后T增加倍数高于无睾丸组织患儿(P<0.05)。结论hCG激发试验对于评估不同类型的DSD患儿的睾丸间质细胞存在和功能均具有重要价值,对于性腺性质不明确的DSD患儿,均建议行hCG激发试验。
文摘We retrospectively assessed long-term pulmonary function in adults surviving for ≥5 years after myeloablative allogeneic hematopoietic stem cell transplantation and identified risk factors for late-onset noninfectious pulmonary complications. Among 174 patients undergoing transplantation for hematologic malignancies between May 1994 and December 2004, 81 long-term survivors were evaluated. Pulmonary function tests (PFTs) were performed before conditioning, 3 months and 1 year after transplantation, and then annually. Eight patients (10%) had abnormal pulmonary function before transplantation, but this was not associated with late changes in PFTs. Patients with chronic graft-versus-host disease (GVHD) showed a significant decline of lung function after 3 years when compared with patients without chronic GVHD. Abnormal pretransplantation lung function was associated with pulmonary chronic GVHD according to National Institutes of Health criteria (score 0, n = 58;score 1, n = 14;score 2, n = 6;score 3, n = 3). Five patients with late-onset noninfectious pulmonary complications showed a decline of lung function at 1 year after transplantation. Only chronic GVHD was significantly related to late-onset noninfectious pulmonary complications. In conclusion, abnormal lung function before transplantation may be associated with a decline in pulmonary function within 1 year after transplantation, but late-onset noninfectious pulmonary complications could not be predicted from pretransplantation lung function.
