Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin （OCN） in predicting diabetes was reported, but with conflicting results. No study has explored...Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin （OCN） in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen （CTX） and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant （NGT） women at baseline were invited for follow-up. The incidence of diabetes and prediabetes （collectively defined as dysglycemia） was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% （95% confidence interval （CI）, 6.8%-30.70/0）] compared with the lower [31.0% （95% CI, 17.2%-46.1%）] and upper [46.5% （95% CI, 31.2%-62.6%）] tertiles of CTX, with a significant difference seen between the middle and upper tertiles （P = 0.002 5）. After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 （95% CI, 1.73-28.99） when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.展开更多
In order to study the characteristics of crustal deformation around the epicenter before the 2016 M_S6. 4 Menyuan earthquake,the GPS continuous stations of the period from 2010 to 2016 were selected according to the o...In order to study the characteristics of crustal deformation around the epicenter before the 2016 M_S6. 4 Menyuan earthquake,the GPS continuous stations of the period from 2010 to 2016 were selected according to the observation data of the tectonic environment monitoring network in Chinese Mainland. The deformation characteristics of the crust before the earthquake were discussed through inter-station baseline time series analysis and the strain time series analysis in the epicentral region. The results show that a trend turn of the baseline movement state around the epicenter region occurred after 2014,and the movement after 2014 reflects an obvious decreasing trend of compressional deformation.During this period,the stress field energy was in a certain accumulation state. Since the beginning of 2014,the EW-component linear strain and surface strain rate weakened gradually before the earthquake. It shows that there was an obvious deformation deficit at the epicentral area in the past two years,which indicates that the region accumulated a high degree of strain energy before the earthquake. Therefore,there was a significant background change in the area before the earthquake. The results of the study can provide basic research data for understanding the seismogenic process and mechanism of this earthquake.展开更多
Limited benefit population of immune checkpoint inhibitors makes it urgent to screen predictive biomarkers for stratifying the patients.Herein,we have investigated peripheral CD4^(+) T cell signatures in advanced non-...Limited benefit population of immune checkpoint inhibitors makes it urgent to screen predictive biomarkers for stratifying the patients.Herein,we have investigated peripheral CD4^(+) T cell signatures in advanced non-small cell lung cancer(NSCLC)patients receiving anti-PD-1/PD-L1 treatments.It was found that the percentages of IFN-γand IL-17A secreting naïve CD4^(+) T cells(Tn),and memory CD4^(+) T cells(Tm)expressing PD-1,PD-L1 and CTLA-4 were significantly higher in responder(R)than non-responder(NonR)NSCLC patients associated with a longer progression free survival(PFS).Logistic regression analysis revealed that the baseline IFN-γ-producing CD4^(+) Tn cells and PD-1^(+)CD4^(+) Tm cells were the most significant signatures with the area under curve(AUC)value reaching 0.849.This was further validated in another anti-PD-1 monotherapy cohort.Conversely,high percentage of CTLA-4^(+)CD4^(+) Tm cells was associated with a shorter PFS in patients receiving anti-PD-L1 monotherapy.Our study therefore elucidates the significance of functional CD4^(+) Tn and Tm subpopulations before the treatment in predicting the responses to anti-PD-1 treatment in Chinese NSCLC patients.The fact that there display distinct CD4^(+) T cell signatures in the prediction to anti-PD-1 and anti-PD-L1 monotherapy from our study provides preliminary evidence on the feasibility of anti-PD-1 and anti-PD-L1 combination therapy for advanced NSCLC patients.展开更多
基金supported by projects from the National Natural Science Foundation of China(81370977,81570796 and 81370018)by the Shanghai Science and Technology Committee(14411960900)
文摘Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin （OCN） in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen （CTX） and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant （NGT） women at baseline were invited for follow-up. The incidence of diabetes and prediabetes （collectively defined as dysglycemia） was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% （95% confidence interval （CI）, 6.8%-30.70/0）] compared with the lower [31.0% （95% CI, 17.2%-46.1%）] and upper [46.5% （95% CI, 31.2%-62.6%）] tertiles of CTX, with a significant difference seen between the middle and upper tertiles （P = 0.002 5）. After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 （95% CI, 1.73-28.99） when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.
基金funded by the Earthquake Science and Technology Development Fund of GEA(Grant No.2016M02,2016Y02)the Earthquake Tracking Task of CEA(2017010221)+1 种基金the Fund of Science for Earthquake Resilience,CEA,(XH16038Y,XH14049)Grant of National Natural Science Foundation of China(51408567,41304048)
文摘In order to study the characteristics of crustal deformation around the epicenter before the 2016 M_S6. 4 Menyuan earthquake,the GPS continuous stations of the period from 2010 to 2016 were selected according to the observation data of the tectonic environment monitoring network in Chinese Mainland. The deformation characteristics of the crust before the earthquake were discussed through inter-station baseline time series analysis and the strain time series analysis in the epicentral region. The results show that a trend turn of the baseline movement state around the epicenter region occurred after 2014,and the movement after 2014 reflects an obvious decreasing trend of compressional deformation.During this period,the stress field energy was in a certain accumulation state. Since the beginning of 2014,the EW-component linear strain and surface strain rate weakened gradually before the earthquake. It shows that there was an obvious deformation deficit at the epicentral area in the past two years,which indicates that the region accumulated a high degree of strain energy before the earthquake. Therefore,there was a significant background change in the area before the earthquake. The results of the study can provide basic research data for understanding the seismogenic process and mechanism of this earthquake.
基金supported by the National Key Research and Development Program of China(2016YFC1303303)the National Natural Science Foundation of China(82073152,81802264)+1 种基金Technology Innovation Program of Shanghai(19411950500)Talent Training Program of Shanghai Chest Hospital in 2019,and Incubation Project Plan for Research in Shanghai Chest Hospital(2019YNJCM07)。
文摘Limited benefit population of immune checkpoint inhibitors makes it urgent to screen predictive biomarkers for stratifying the patients.Herein,we have investigated peripheral CD4^(+) T cell signatures in advanced non-small cell lung cancer(NSCLC)patients receiving anti-PD-1/PD-L1 treatments.It was found that the percentages of IFN-γand IL-17A secreting naïve CD4^(+) T cells(Tn),and memory CD4^(+) T cells(Tm)expressing PD-1,PD-L1 and CTLA-4 were significantly higher in responder(R)than non-responder(NonR)NSCLC patients associated with a longer progression free survival(PFS).Logistic regression analysis revealed that the baseline IFN-γ-producing CD4^(+) Tn cells and PD-1^(+)CD4^(+) Tm cells were the most significant signatures with the area under curve(AUC)value reaching 0.849.This was further validated in another anti-PD-1 monotherapy cohort.Conversely,high percentage of CTLA-4^(+)CD4^(+) Tm cells was associated with a shorter PFS in patients receiving anti-PD-L1 monotherapy.Our study therefore elucidates the significance of functional CD4^(+) Tn and Tm subpopulations before the treatment in predicting the responses to anti-PD-1 treatment in Chinese NSCLC patients.The fact that there display distinct CD4^(+) T cell signatures in the prediction to anti-PD-1 and anti-PD-L1 monotherapy from our study provides preliminary evidence on the feasibility of anti-PD-1 and anti-PD-L1 combination therapy for advanced NSCLC patients.
